top of page

Biomedical Basis for Herbs as Anti-angiogenic Agents: Chinese Herbal Medicine in Cancer Care

Updated: Jun 20, 2019

The interest in "natural" treatments for cancer is increasing. But are they effective? And how might they work? Classical Chinese Herbal medicine contains many herbal formulas used for management of patients diagnosed with cancer. When the goal of herbal therapy interventions is to assist in tumor control, herbs may be helpful in strategies aimed at starving the tumor of its blood supply. This is called "Antiangiogenic therapy". Antiangiogenic therapy is typically considered an appropriate treatment approach when the goal is to slow or halt tumor growth or prevent metastasis, maintaining good quality life. Read on for the science behind antiangiogenic mechanisms of herbs.

An integrative approach to cancer treatment should target many pathways of tumor progression from a physiological and biochemical standpoint while minimizing normal tissue toxicity and supporting overall well-being. Cancer development and progression requires a complex cascade of events. Each of these pathways is a potential target for anti-cancer therapy. Targeting one of these pathways is unlikely to result in significant tumor control. The potential benefit of herbal therapies in anti-cancer strategies stems from the ability of many herbs to target multiple pathways of tumor progression while causing minimal normal tissue toxicity.


Angiogenesis is the process of new blood vessel formation. Angiogenesis is important in both local tumor progression and the ability for cancer cells to spread and develop into tumors at distant sites, a process called "metastasis".

Antiangiogenic therapy targets tumor blood vessels to halt tumor growth and prevent tumor metastasis. It is a popular topic in the forefront of current cancer therapy and much research is being done on targeted therapies designed to inhibit the ability of tumors to form their own blood supply.

A tumor less than 1 mm in diameter can receive oxygen and nutrients by diffusion but any increase results in the need for the tumor to form its own blood supply. Without the ability to form its own blood supply, a tumor cannot grow larger than about 2mm. Tumors this small would be unlikely to cause clinical problems in a patient. If angiogenesis to spreading tumor cells could be stopped, death from tumor metastasis could theoretically be prevented.


The process of "angiogenesis" requires a number of different steps:

1) recruitment of circulating endothelial cells - these are the cells that will eventually form the structure of the blood vessels

2) survival signals to allow these recruited cells to survive at the tumor site

3) formation of these recruited endothelial cells into vascular tubes

4) reorganization to sustain blood flow through these newly formed blood vessel tubes


The normal balance of the processes promoting angiogenesis (pro-angiogenic signals) and inhibiting angiogenesis (anti-angiogenic signals) in tissues is disturbed in tumors due to increased stimuli. These stimuli include hypoxia (low oxygen), low pH (acidic microenvironment), hypoglycemia (low glucose), cytokines, growth factors, and inflammatory mediators such as COX-2 and prostaglandins. Tumor or host cells secrete "pro-angiogenic" molecules in the local tissue microenvironment which bind to receptors on endothelial cells, leading to endothelial cell proliferation, migration, invasion and capillary tube formation.


Antiangiogenic anticancer therapy has a number of promising benefits.

1) There is the potential for a broad spectrum of antitumor activity as the process of angiogenesis is the same across tumor types.

2) Inhibition of tumor vasculature may be targeted without affecting vascularization of normal tissues due to the fact that tumor vasculature has different characteristics than vasculature in normal tissues.

3) Because endothelial cells are not genetically unstable like tumor cells, they are unable to form resistant clones. Targeting endothelial cells may, therefore, be one way to combat the problem of drug resistance in cancer.

4) Because the target (endothelial cells) and goal (cytostatic - or halting growth) of antiangiogenic therapy is different than maximum-tolerated-dose-chemotherapy (MTD Chemotherapy), which generally aims to induce tumor cell suicide (apoptosis) by damaging the tumor cells’ DNA, synergistic activity may be achievable with the combination of these two treatment modalities.


Successful antiangiogenic therapy has the potential to prevent tumor metastasis from overwhelming the body, prolonging survival times in cancer patients. Because angiogenesis is a multistep process, a successful antiangiogenic protocol targets multiple pathways in blood vessel formation in order to induce a clinical response. Vascular endothelial growth factor (VEGF), nuclear factor-kB (NF-kB) and cyclooxygenase-2 (COX-2) are some of the many angiogenic polypeptides that are involved in cancer angiogenesis and are all potential therapeutic targets in antiangiogenic therapy.


Metronomic chemotherapy, is a strategy of chemotherapy administration which uses low doses of oral chemotherapy agents at regular intervals, often daily. This type of treatment aims to inhibit the process of new blood vessel formation, or angiogenesis, that tumors need in order to supply nutrients needed to grow. This treatment can also make it harder for the tumor to hide from the immune system by changing certain immune responses involved in protecting tumor cells from immune system attack.

ANTIANGIOGENIC THERAPY WITH HERBS: Biomedical Rationale and Research


Overexpression of COX-2 has been demonstrated in a variety of veterinary tumors: transitional cell carcinoma, osteosarcoma, melanoma, prostate adenocarcinoma, canine oral squamous cell carcinoma, canine renal carcinoma, canine nasal carcinoma, canine mammary carcinoma, and feline mammary carcinoma. Canine tumor types shown to lack COX-2 expression are hemangiosarcoma, histiocytic sarcoma, and mast cell tumors. COX-2 converts arachadonic acid into Prostaglandins (PGE) and thromboxanes. PGE2 contributes to tumor cell growth, immunosuppression and angiogenesis. It stimulates angiogenesis and vasodilation. COX-2 also stimulates synthesis of a signaling molecule called vascular endothelial growth factor (VEGF) which is important in the angiogenic process.

Many herbs that inhibit COX-2 do so by blocking the amplified activity of NF-kB (a COX-2 transcription factor) without affecting normal function.

Some Chinese Herbs that have been shown to inhibit COX-2

Ginger (Sheng Jiang, Gan Jiang)

Licorice (Gan Cao)

Chinese skullcap (Huang Qin; Scuttelaria)

Boswellia (Ru Xiang; Frankincense)

Ginseng (Ren Shen; Panax Ginseng)

Turmeric (Yin Zhu, E Zhu, Jiang Huang; Curcuma)

Of particular interest are panax ginseng and curcumin which are adaptogens whose antiangiogenic activity is at least in part due to COX-2 inhibition via inactivation of NF-kB (see below).

Other herbs which have shown ability to inhibit COX-2 are bilberry, aloe vera, green tea, and milk thistle.


Vascular Endothelial Growth Factor (VEGF) stimulates angiogenesis, permeability, leukocyte adhesion, and integrates angiogenic and survival signals. It is an important player in what is called the "angiogenic switch". The angiogenic switch refers to conversion of non-angiogenic tumor cells to angiogenesis inducers by way of release of angiogenic factors. Hypoxia (low oxygen) is one of the primary triggers of VEGF activation. Other triggering factors include COX-2 and growth factors such as EGF, bFGF, IL-1, IL-6, and TGF. VEGF binds to its receptors which trigger downstream signals that lead to inhibition of apoptosis (programmed cell suicide), stimulation of cell division, and degradation of the extracellular matrix which is required for blood vessel formation and also for tumor cells to escape to other areas of the body.

VEGF stimulates proliferation and migration of endothelial cells. It has been shown to stimulate vascular growth, enhancing tumor growth and metastasis is several animal models. VEGF is commonly over-expressed by cancer cells and has been associated with poor prognosis in many malignancies. Higher VEGF levels have been associated with more aggressive tumors and shorter time to radiation treatment failure in dogs with spontaneously arising cancers. In veterinary medicine, VEGF expression has been associated with canine and feline mammary carcinoma, osteosarcoma metastasis, hemangiosarcoma, and canine meningioma, canine nasal tumors, mast cell tumors, canine cutaneous and digital squamous cell carcinoma, canine lymphoma, soft tissue sarcomas, and various intracranial tumors.

Traditional Chinese Medicine Herbs That Inhibit VEGF:

Chinese Skullcap (Huang Qin; Scuttelaria baicalensis )

Scrophularia (Xuan Shen; Scrophularia ningpoensis )

Coptis (Huang Lian; Coptis chinensis )

Turmeric (Jiang Huang; Curcuma longa )

Angelica root (Dang Gui Shen, Angelica sinensis )

Magnolia bark (Huo Po; Magnolia obovata)

Ginger (Sheng Jiang and Gan Jiang; Zingiber officianale )

Chinese Wormwood (Qing Hao; Artemesia annua)


Nuclear Factor-kB (NF-kB) is one of the primary transcription factors in the cell survival pathway. It is activated by various cytokines, including TNF-a (tumor necrosis factor-alpha). Activation of NF-kB suppresses apoptosis (cell suicide). Inhibition of NF-kB results in enhanced apoptosis. NF-kB does much more than modulate the process of cell death, however. It regulates the expression of over 400 genes involved in inflammation, cell survival, proliferation, angiogenesis and immune responses. NF-kB is involved in the upregulation of multidrug resistance and blocks apoptosis induced by cytotoxic agents such as chemotherapy, radiation and oxidative damage. Of particular importance in antiangiogenic therapy, VEGF and COX-2 activation are induced by NF-kb.

Inflammation via the NF-kB pathway has been linked to the development of cancer in many studies. NF-kB suppression was shown to prevent liver cancer progression in a mouse model. Similarly, suppression of NF-kB signaling prevented development of liver carcinoma (HCC) in the established HCC model mdr2-knockout mouse. Rapid tumor development occurred with reactivation of NF-kb.

NF-kB is activated by radiation therapy and has been linked to radiation resistance in many tumors. More specifically, NF-kB activation has been linked to development of radiation and chemotherapy resistance in solid tumors and its expression is induced in response to radiation and many chemotherapy drugs. Inhibition of NF-kB, therefore, becomes an interesting method by which development of chemotherapy resistance may be limited, or by which chemotherapy sensitivity may be enhanced.

Within earlier literature, there exists concern that inhibition of NF-kB or other antioxidant therapies may reduce the effectiveness of chemotherapeutic agents. In particular, it has been proposed that some of Adriamycin’s cytotoxic activity is through activation of NF-kB. While there are studies showing that NF-kB can inhibit the expression of certain anti-apoptotic genes, these reports do not examine the overall effects of NF-kB inhibition on Adriamycin sensitivity and there is little evidence that NF-kB inhibition actually decreases the effectiveness of chemotherapy.

On the contrary, NF-kB inhibition (using a small molecule inhibitor of IKKb) was specifically proven in one study to actually enhance the cell killing ability of Adriamycin chemotherapy. This study evaluated whether NF-kB proved to be pro-apoptotic or anti-apoptotic in Adriamycin-treated osteosarcoma cells. The study showed that the ability of Adriamycin to inhibit expression of anti-apoptotic (survival) genes such as Survivin, Bcl-2 and Bcl-xL was through mechanisms other than NF-kB. Additionally, Adriamycin-induced NF-kB expression was actually shown to decrease the apoptotic activity of Adriamcyin and NF-kB inhibition improved apoptotic cell death in Adriamycin-treated osteosarcoma cells. NF-kB expression was linked with the ability of osteosarcoma cells to resist the cytotoxic effects of Adriamycin. With the combination therapy, equivalent cytotoxicity was able to be achieved using 75% less Adriamycin.

Chinese Herbs that inhibit NF-kB include

Turmeric (Jiang Huang, Yin Zhu, E Zhu; Curcuma)

Ginger (Sheng Jiang, Gan Jiang)

Ginseng (Ren Shen; Panax Ginseng)

Chinese wormwood (Qing Hao; Artemesia annua)

Other: resveratrol, green tea, holy basil

CHINESE HERBAL FORMULAS: Compounds with Research on Angiogenic Action

Xiao Chai Hu Tang

Panax ginseng (Ren Shen) contains saponins, or ginsenosides, which have been shown to have antiangiogenic action and induce apoptosis in cancer cells. Ginseng was shown to inhibit NF-kB and enhance the susceptibility of colon cancer cells to chemotherapy in vitro when compared to chemotherapy alone. It has shown anti-proliferative effects on hepatocellular carcinoma cells. It was also shown to have synergistic activity when used with gemcitabine against lung carcinoma in mice and decreased tumor VEGF expression.

Ginger (Sheng Jiang, Gan Jiang) inhibits VEGF and bFGF and causes cell cycle arrest. At doses lower than cytotoxic levels, it decreased the number of lung metastasis in mice injected with melanoma cells. Ginger also has been shown to inhibit NF-kB.

Chinese Skullcap (Huang Qin; Scuttelaria baicalensis) contains baicalin and baicalein which are potent antiangiogenic compounds via their ability to inhibit VEGF, bFGF, 12-lipoxygenase and MMP.

Rhubarb (Da Huang; Rheum palmatum) contains emodin which reduced angiogenesis and reduced breast carcinoma growth in vivo.

Modified Xue Fu Zhu Yu Tang

Angelica Root (Dang Gui Wei) has been shown to inhibit VEGF in numerous laboratory studies. An in vivo study of transgenic adenocarcinoma in mouse prostate, it was shown to decrease expression of FGF2, decrease expression of genes related to inflammation and angiogenesis, and increase expression of many tumor suppressor genes.

Safflower (Hong Hua; Carthamus tinctorius) contains hydroxysafflor yellow A inhibited angiogenesis in mice bearing hepatoceullar carcinoma through mechanisms involving down regulation of MMP-2 and MMP-9. COX-2 expression was down regulated through inhibition of MAPK signaling pathways. It also inhibits NF-bK.

Turmeric (Jiang Huang, Yin Zhu, E Zhu; Curcuma longa) contains curcumin, which has been shown to enhance cytotoxicity when used in conjunction with chemotherapy and radiation. Curcumin has been shown to suppress NF-kB activation. By this mechanism, it enhances the sensitivity of colorectal cells to fractionated radiation therapy and inhibits angiogenesis. It decreases NF-kB-regulated gene products such as cyclin-D, c-myc, Bcl-2, Bcl-xL, COX-2, MMP-9 and VEGF which are induced by radiation therapy and implicated in development of radiation resistance. Curcumin was shown to potentiate the antitumor effect of gemcitabine in pancreatic cancer cells both in vivo and vitro. This action was attributed to curcumin’s ability to suppress proliferation, angiogenesis, NF- and NF--regulated gene products.

The following antiangiogenic effects have been demonstrated for curcumin: downregulation of MMP-2 and upregulation of TIMP-1, inhibition of VEGF and bFGF transcription, binds to angiopoietin (APN) and blocks its activity, inhibition of MMP-9 and MMP-2 activity, inhibition of growth factor receptors such as VEGFR and EGFR. An in vivo study confirmed biological activity with oral ingestion of dietary curcumin in mice resulting in slowed growth of implanted human pancreatic tumors and measurable decrease in NF-kB and NF-kB-related gene products.

Other Herbs containing Compounds that have Demonstrated Antiangiogenic Action

Magnolia officinalis (Huo Po; chinese magnolia tree) contains the antiangiogenic agent honokiol which alters expression of PDGF, TGF-band TNF-a. Additionally, in animal models, it was shown to decrease tumor growth via inhibition of vascular endothelial cells.


While there are no "magic bullets" for cancer cure yet, herbal therapies do hold promise as effective tools in our anticancer toolbox. There are many laboratory studies demonstrating the anticancer effects of herbs and providing proof of principle for the use of herbs as antiangiogenic agents in cancer treatment. I have treated many patients with herbal therapies alone and seen cancer remissions. However, not every patients or cancer type will respond to herbal therapies, just like not every patient will respond to chemotherapy. It is important to be well-informed about the pros and cons of herbal treatment in cancer therapy for pets and understand that, while there is substantial biomedical basis for use of herbs in cancer treatment, there are still many unanswered questions. As with any therapy, this course of treatment should be embarked upon with informed consent and proper guidance. If you are interested in herbal medicine, talk with your veterinarian trained in herbal medicine about expected responses and whether your pet may be a candidate for this type of therapy.


1) Hanahan D, Weinberg RA. The hallmarks of cancer. Cell.2000;100:57-70.

2) Plummer SM, Kaptein A, Farro S, et al. Inhibition of cyclooxygenase-2 expression in colon cells by the chemopreventative agent curcumin involves inhibition of NF-kbactivation via the NIK/IKK signaling complex. Oncogene. 1999;16:6013-6020.

3) Maraveyas A, Lam T, Hetherington JW, et al. Can a rational design for metronomic chemotherapy dosing be devised? Br J Cancer. 2005;92:1588-1590.

4) Hudis CA. Clinical implications of antiangiogenic therapies. Oncology. 2005;19(4 suppl 3):26-31.

5) Harrison MR, Huang W, Liu G, et al. Response to antiangiogenesis therapy in a patient with advanced adult-type testicular granulosa cell tumor. Oncology. 2009 Aug;23(9):796.

6) Makrilia N, Lappa T, Xyla V, et al. The role of angiogenesis in solid tumours: an overview. Eur J Intern Med. 2009 Nov;20(7):663-71.

7) Lee JY, Tanabe S, Shimohira H, et al. Expression of cyclooxygenase-2, P-glycoprotein and multi-drug resistance-associated protein in canine transitional cell carcinoma. Res Vet Sci. 2007 Oct;83(2):210-6.

8) Khan KN, Knapp DW, Denicola DB, et al. Expression of cyclooxygenase-2 in transitional cell carcinoma of the urinary bladder in dogs. Am J Vet Res. 2000 May;61(5):478-81.

9) Mullins MN, Lana SE, Dernell WS, et al. Cyclooxygenase-2 expression in canine appendicular osteosarcomas. J Vet Intern Med. 2004 Nov-Dec;18(6):859-65.

10) Mohammed SI, Khan KN, Sellers RS, et al. Expression of cyclooxygenase-1 and 2 in naturally-occurring canine cancer. Prostaglandins Leukot Essent Fatty Acids. 2004 May;70(5):479-83.

11) Sorenmo KU, Goldschmidt MH, Shofer FS, et al. Evaluation of cyclooxygenase-1 and cyclooxygenase-2 expression and the effect of cyclooxygenase inhibitors in canine prostatic carcinoma. Vet Comp Oncol. 2004 Mar;2(1):13-23.

12) Khan KN, Stanfield KM, Trajkovic D, et al. Expression of cyclooxygenase-2 in canine renal cell carcinoma. Vet Pathol. 2001 Jan;38(1):116-9.

13) Impellizeri JA, Esplin DG. Expression of cyclooxygenase-2 in canine nasal carcinomas. Vet J. 2008 Jun;176(3):408-10.

14) Kleiter M, Malarkey DE, Ruslander DE, et al Expression of cyclooxygenase-2 in canine epithelial nasal tumors. Vet Radiol Ultrasound. 2004 May-Jun;45(3):255-60.

15) Borzacchiello G, Paciello O, Papparella S. Expression of cyclooxygenase-1 and -2 in canine nasal carcinomas. J Comp Pathol. 2004 Jul;131(1):70-6.

16) Millanta F, Citi S, Della Santa D, et al. COX-2 expression in canine and feline invasive mammary carcinomas: correlation with clinicopathological features and prognostic molecular markers. Breast Cancer Res Treat. 2006 Jul;98(1):115-20.

17) Lavalle G, Bertagnolli A, Tavares W, et al. COX-2 expression in canine mammary carcinomas: correlation with angiogenesis (or microvessel density) and overall survival. Vet Pathol. 2009 Jul 15.

18) de M Souza CH, Toledo-Piza E, Amorin R, et al. Inflammatory mammary carcinoma in 12 dogs: clinical features, cyclooxygenase-2 expression, and response to piroxicam treatment. Can Vet J. 2009 May;50(5):506-10.

19) Dias Pereira P, Lopes CC, Matos AJ, et al. COX-2 expression in canine normal and neoplastic mammary gland. J Comp Pathol. 2009 May;140(4):247-53.

20) Millanta F, Citi S, Della Santa D, et al. COX-2 expression in canine and feline invasive mammary carcinomas: correlation with clinicopathological features and prognostic molecular markers. Breast Cancer Res Treat. 2006 Jul;98(1):115-20.

21) Sayasith K, Sirois J, Doré M. Molecular characterization of feline COX-2 and expression in feline mammary carcinomas. Vet Pathol. 2009 May;46(3):423-9.

22) Heller DA, Clifford CA, Goldschmidt MH, Holt DE, Manfredi MJ, Sorenmo KU. Assessment of cyclooxygenase-2 expression in canine hemangiosarcoma, histiocytic sarcoma, and mast cell tumor. Vet Pathol. 2005 May;42(3):350-3.

23) Wallace JM. Nutritional and botanical modulation of the inflammatory cascade: eicosanoids, cyclooxygenases, and lipoxygenases as an adjunct in cancer therapy. Integr Cancer Ther. 2002;1:7-37.

24) Sturk C, Dumont D. Angiogenesis. In: Tannock IF, Hill RP, et al. The Basic Science of Oncology, 4thed. USA: The McGraw-Hill Companies, 2005: 232-234.

25) Folkman J. How is blood vessel growth regulated in normal and neoplastic tissue? GHC Clowes Memorial Reward Lecture. Cancer Res. 1986;46:467-473.

26) Risau W. Mechanisms of angiogenesis. Nature. 1997;386:671-674.

27) Kumar R, Yoneda J, Bucana CD, Fidler IJ. Regulation of distinct steps of angiogenesis by different angiogenic molecules. Int J Oncol. 1998;12:749-757.

28) Wergin MC, Kaser-Hotz B. Plasma vascular endothelial growth factor (VEGF) measured in seventy dogs with spontaneously occurring tumours. In Vivo. 2004 Jan-Feb;18(1):15-9.

29) Wergin MC, Roos M, Inteeworn N, et al. The influence of fractionated radiation therapy on plasma vascular endothelial growth factor (VEGF) concentration in dogs with spontaneous tumors and its impact on outcome. Radiother Oncol. 2006 May;79(2):239-44.

30) Millanta F, Silvestri G, Vaselli C, et al. The role of vascular endothelial growth factor and its receptor Flk-1/KDR in promoting tumour angiogenesis in feline and canine mammary carcinomas: a preliminary study of autocrine and paracrine loops. Res Vet Sci. 2006 Dec;81(3):350-7.

31) Kato Y, Asano K, Mizutani I, et al. Gene expressions of canine angiopoietin-1 and -2 in normal tissues and spontaneous tumours. Res Vet Sci. 2006 Oct;81(2):280-6.

32) Qiu CW, Lin DG, Wang JQ, et al. Expression and significance of PTEN and VEGF in canine mammary gland tumours. Vet Res Commun. 2008 Aug;32(6):463-72.

33) Millanta F, Silvestri G, Vaselli C, et al. The role of vascular endothelial growth factor and its receptor Flk-1/KDR in promoting tumour angiogenesis in feline and canine mammary carcinomas: a preliminary study of autocrine and paracrine loops. Res Vet Sci. 2006 Dec;81(3):350-7.

34) Thamm DH, O'Brien MG, Vail DM. Serum vascular endothelial growth factor concentrations and postsurgical outcome in dogs with osteosarcoma. Vet Comp Oncol.2008 Jun;6(2):126-32.

35) Clifford CA, Hughes D, Beal MW, et al. Plasma vascular endothelial growth factor concentrations in healthy dogs and dogs with hemangiosarcoma. J Vet Intern Med. 2001 Mar-Apr;15(2):131-5.

36) Matiasek LA, Platt SR, Adams V, et al. Ki-67 and vascular endothelial growth factor expression in intracranial meningiomas in dogs. J Vet Intern Med.2009 Jan-Feb;23(1):146-51.

37) Platt SR, Scase TJ, Adams V, et al. Vascular endothelial growth factor expression in canine intracranial meningiomas and association with patient survival. J Vet Intern Med. 2006 May-Jun;20(3):663-8.

38) Shiomitsu K, Johnson CL, Malarkey DE, et al. Expression of epidermal growth factor receptor and vascular endothelial growth factor in malignant canine epithelial nasal tumours. Vet Comp Oncol. 2009 Jun;7(2):106-14.

39) Patruno R, Arpaia N, Gadaleta CD, et al. VEGF concentration from plasma-activated platelets rich correlates with microvascular density and grading in canine mast cell tumour spontaneous model. J Cell Mol Med. 2009 Mar;13(3):555-61.

40) Al-Dissi AN, Haines DM, Singh B, et al. Immunohistochemical expression of vascular endothelial growth factor and vascular endothelial growth factor receptor associated with tumor cell proliferation in canine cutaneous squamous cell carcinomas and trichoepitheliomas. Vet Pathol. 2007 Nov;44(6):823-30.

41) Maiolino P, De Vico G, Restucci B. Expression of vascular endothelial growth factor in basal cell tumours and in squamous cell carcinomas of canine skin. J Comp Pathol. 2000 Aug-Oct;123(2-3):141-5.

42) Wolfesberger B, Tonar Z, Witter K, et al. Microvessel density in normal lymph nodes and lymphomas of dogs and their correlation with vascular endothelial growth factor expression. Res Vet Sci. 2008 Aug;85(1):56-61.

43) Wolfesberger B, Guija de Arespacohaga A, Willmann M, et al. Expression of vascular endothelial growth factor and its receptors in canine lymphoma. J Comp Pathol. 2007 Jul;137(1):30-40.

44) Gentilini F, Calzolari C, Turba ME, et al. Prognostic value of serum vascular endothelial growth factor (VEGF) and plasma activity of matrix metalloproteinase (MMP) 2 and 9 in lymphoma-affected dogs. Leuk Res. 2005 Nov;29(11):1263-9.

45) Kamstock D, Elmslie R, Thamm D, et al. Evaluation of a xenogeneic VEGF vaccine in dogs with soft tissue sarcoma. Cancer Immunol Immunother. 2007 Aug;56(8):1299-309.

46) Rossmeisl JH, Duncan RB, Huckle WR, et al. Expression of vascular endothelial growth factor in tumors and plasma from dogs with primary intracranial neoplasms. Am J Vet Res. 2007 Nov;68(11):1239-45.

47) Yance DR, Sager SM. Targeting angiogenesis with integrative cancer therapies. Integrative Cancer Therapies. 2006;5(1):9-29.

48)Bednarski, et al. Antioxid Redox Signal. 2009 Jan; 11(1): 99–134 (out of MD Anderson)

49) D'acquisto F, Lanzotti V, Carnuccio R. Cyclolinteinone, a sesterterpene from sponge Cacospongia linteiformis, prevents inducible nitric oxide synthase and inducible cyclo-oxygenase protein expression by blocking nuclear factor-k B activation in J774 macrophages. BiochemJ. 2000;346:793-8.

50) Nagaya T, Imai T, Funahashi H, et al. Inhibition of NF-kappaB activity decreases the VEGF mRNA expression in MDA-MB-231 breast cancer cells. Breast Cancer Res Treat.2002;73:237-43.

51) Huang S, Robinson JB, Deguzman A, et al. Blockade of nuclear factor-kappaB signaling inhibits angiogenesis and tumorigenicity of human ovarian cancer cells by suppressing expression of vascular endothelial growth factor and interleukin 8.Cancer Res2000;60:5334-5339.

52) Jiali Zhang and Bin Peng. In vitro angiogenesis and expression of nuclear factor κB and VEGF in high and low metastasis cell lines of salivary gland Adenoid Cystic Carcinoma. BMC Cancer2007;7:95

53) Gilmore TD: Introduction to NF-kappaB: players, pathways,perspectives.Oncogene2006;25:6680-6684.

54) Dolcet X, Llobet D, Pallares J, et al: NF-kB in development and progression of human cancer. Virchows Arch2005, 446:475-482.

55) Pikarsky E, Porat RM, Stein I, et al. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature.2004;431:461–466.

56) Wang CY, Mayo MW, Baldwin AS, Jr. TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB. Science. 1996;274: 784–787.

57) Voboril R, Weberova-Voborilova J. Constitutive NF-kbactivity in colorectal cancer cells: impact on radiation-induced NF-kbactivity, radiosensitivity, and apoptosis. Neoplasma. 2006;53:518-123.

58) Weichselbaum RR, Hallahan D, Fuks Z, et al. Radiation induction of immediate early genes: effectors of the radiation stress response. Int J Radiat Oncol Biol Phys. 1994;30:229-234.

59) Aggarwal BB. Nuclear-factor-kb: the enemy within. Cancer Cell. 2004;6:203-208.

60) Wang CY, Guttridge DC, Mayo MW, et al. NF-kappaB induces expression of the Bcl-2 homologue A1/Bfl-1 to preferentially suppress chemotherapy- induced apoptosis. Mol Cell Biol. 1999;19:5923–5929.

61) Cusack JC, Jr., Liu R, Baldwin AS, Jr. Inducible chemoresistance to 7-ethyl-10- [4-(1-piperidino)-1-piperidino]-carbonyloxycamptothe cin (CPT-11) in colorectal cancer cells and a xenograft model is overcome by inhibition of nuclear factor- kappaB activation. Cancer Res. 2000;60: 2323–2330.

62) Cusack JC, Jr., Liu R, Houston M, et al. Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition. Cancer Res. 2001;61: 3535–3540.

63) Chen W, Wang X, Bai L, et al. Blockage of NF- kappaB by IKKbeta- or RelA-siRNA rather than the NF-kappaB super- suppressor IkappaBalpha mutant potentiates adriamycin-induced cytotoxicity in lung cancer cells. J Cell Biochem2008;105: 554–561.

64) Gangadharan C, Thoh M, Manna SK. Inhibition of constitutive activity of nuclear transcription factor kappaB sensitizes doxorubicin-resistant cells to apoptosis. J Cell Biochem. activity. Br J Pharmacol. 2009;145: 178–192.

65) Campbell KJ, Rocha S, Perkins ND. Active repression of antiapoptotic gene expression by RelA(p65) NF-kappa B. Mol Cell. 2004;13: 853–865.

66) Ho WC, Dickson KM, Barker PA. Nuclear factor-kappaB induced by doxorubicin is deficient in phosphorylation and acetylation and represses nuclear factor-kappaB-dependent transcription in cancer cells. Cancer Res.2005;65: 4273–4281.

67) Bednarski BK, Baldwin AS Jr, Kim HJ. Addressing reported pro-apoptotic functions of NF-kappaB: targeted inhibition of canonical NF-kappaB enhances the apoptotic effects of doxorubicin. PLoS One. 2009 Sep 10;4(9):e6992.

68) Pendurthi UR, Williams JT, Rao LV. Inhibition of tissue factor gene activation in cultured endothelial cells by curcumin: suppression of activation of transcription factors Egr-1, AP-1, and NF-kb. Arterioscler Thromb Vasc Biol. 1997;17:3406-3413.

69) Jobin C, Bradham CA, Russo MP, et al. Curcumin blocks cytokine-mediated NF-kbactivation and proinflammatory gene expression by inhibiting inhibitory factor Ikbkinase activity. J Immunol. 1999;163:3474-3483.

70) Bharti AC, Donato N, Singh S, et al. Curcumin down-regulates the constitutive activation of nuclear factor-kappa band Ikappabalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood. 2003;101:1053-1062.

71) Siwak DR, Shishodia S, Aggarwal BB, et al. Curcumin-induced antiproliferative and apoptotic effects in melanoma cells are associated with suppression of Ikappabkinase and nuclear factor kappabactivity and are independent of the B-Raf/mitogen-activated extracellular signal related protein kinase pathway and the Akt pathway. Cancer. 2005;104:879-890.

72) Oh GS, Pae HO, Choi BM, et al. 20(S)-Protopanaxatriol, one of ginsenoside metabolites, inhibits inducible nitric oxide synthase and cyclooxygenase-2 expression through inactivation of nuclear factor-kappabin RAW 264.7 macrophages stimulated with lipopolysaccharide. Cancer Lett. 2004;205:23-29.

73) Aldieri E, Atragene D, Bergandi L, et al. Artemesinin inhibits inducible nitric oxide synthase and nuclear factor NF-kbactivation. FEBS Lett. 2003;552:141-144.

74) Sen S, Sharma H, Singh N. Curcumin enhances vinorelbine mediated apoptosis in NSCLC cells by the mitochondrial pathway. Biochem Biophys Res Commun. 2005;331:1245-1252.

75) Khafif A, Hurst R, Kyker K, et al. Curcumin: a new radiosensitizer of squamous cell carcinoma cells. Otolaryngol Head Neck Surg. 2005;132:317-321.

76) Kunnumakkara AB, Diagaradjane P, Guha S, et al. Curcumin sensitizes human colorectal cancer xenografts in nude mice to g-radiation by targeting nuclear factor-kb- regulated gene products. Clin Cancer Res.2008;14(7): 2128-2136.

77) Kunnumakkara AB, Guha S, Krishnan S, et al. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kb-regulated gene products. Cancer Res. 2007;67(8):3853-61.

78) Shao ZM, Shen ZZ, Liu CH, et al. Curcumin exerts multiple suppressive effects on human breast carcinoma cells. Int J Cancer. 2002;98:234-240.

79) Arbiser JL, Klauber N, Rohan R, et al. Curcumin is an in vivo inhibitor of angiogenesis. Mol Med. 1998;4:376-383.

80) Gururaj AE, Belakavadi M, Venkatesh DA, et al. Molecular mechanisms of antiangiogenic effect of curcumin. Biochem Biophys Res Commun. 2002;297:934-942.

81) Shim JS, Kim JH, Cho HY, et al. Irreversible inhibition of CD13/aminopeptidase-N by the antiangiogenic agent curcumin. Chem Biol. 2003;10:695-704.

82) Chen HW, Yu SL, Chen JJ, et al. Anti-invasive gene expression profile of curcumin in lung adenocarcinoma based on a high throughput microarray analysis. Mol Pharmacol. 2004;65:99-110.

83) Dorai T, Cao YC, Dorai B, et al. Therapeutic potential of curcumin in prostate cancer-III: curcumin inhibits proliferation , induces apoptosis and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate. 2001;47:293-303.

84) Leu TH, Su SL, Chuang YC, et al. Direct inhibitory effect of curcumin on src and focal adhesion kinase activity. Biochem Pharmacol. 2003;66:2323-2331.

85) Bimonte S, Barbieri A, Palma G, et al. Curcumin inhibits tumor growth and angiogenesis in an orthotopic mouse model of human pancreatic cancer. Biomed Res Int.2013;2013:810423

86) Cheng AL, Hsu SL, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk pre-malignant lesions. Anticancer Res. 2001;21:2895-2900.

87) Fu Z, Chen X, Guan S, et al. Curcumin inhibits angiogenesis and improves defective hematopoiesis induced by tumor-derived VEGF in tumor model through modulating VEGF-VEGFR2 signaling pathway. Oncotarget. 2015 Aug 14;6(23):19469-82.88) Wang ZY, Nixon DW. Licorice and cancer. Nutr Cancer. 2001;39:1-11.

89) Singh NP, Lai HC. Artemesinin induces apoptosis in human cancer cells. Anticancer Res. 2004;24:2277-2280.

90) Chen HH, Zhou HJ, Wu GD, et al. Inhibitory effects of artesunate on angiogenesis and on expression of vascular endothelial growth factor and VEGF receptor KDR/flk1. Pharmacology. 2004;7:1-9.

91) Sato K, Mochizuki M, Saiki I, et al. Inhibition of tumor angiogenesis and metastasis by a saponin of Panax ginseng, ginsenoside-Rb2. Biol Pharm Bull. 1994;17:645-639.

92) Kim SM, Lee SY, Yuk DY, et al. Inhibition of NF-kappaB by ginsenoside Rg3 enhances the susceptibility of colon cancer cells to docetaxel. Arch Pharm Res. 2009;32(5):755-65.

93) Guo L, Song L, Wang Z, et al. Panaxydol inhibits the proliferation and induces the differentiation of human hepatocarcinoma cell line HepG2. Chem Biol Interact. 2009 Sep 14;181(1):138-43.

94) Liu TG, Huang Y, Cui DD, Huang XB, Mao SH, Ji LL, Song HB, Yi C. Inhibitory effect of ginsenoside Rg3 combined with gemcitabine on angiogenesis and growth of lung cancer in mice. BMC Cancer. 2009 Jul 23;9:250.

95) Kim EC, Min JK, Kim TY, et al. [6]-Gingerol, a pungent ingredient of ginger, inhibits angiogenesis in vitro and in vivo. Biochem Biophys ResCommun. 2005;335:300-308.

96) Bode AM, Ma WY, Surh YJ, et al. Inhibition of epidermal growth factor induced cell transformation and AP1 activation by (6)-gingerol. Cancer Res. 2001;61:850-853.

97) Liu JJ, Huang TS, Cheng WF, et al. Baicalein and baicalin are potent inhibitors of angiogenesis: inhibition of endothelial cell proliferation, migration and differentiation. Int J Cancer. 2003;106:559-565.

98) Miocinovic R, McCabe NP, Keck RW, et al. In vivo and in nitro effect of baicalein on human prostate cancer cells. Int J Oncol. 2005;26:241-246.

99) Lee BC, Doo HK, Lee HJ, et al. The inhibitory effects of aqueous extract of Magnolia officinalis on human mesangial cell proliferation by regulation of platelet derived growth factor-BB and transforming growth factor beta1 expression. J Pharmacol Sci. 2004;94:81-85.

100) Son HJ, Lee HJ, Yun-Choi HS, et al. Inhibitors of nitric oxide synthesis and TNF-alpha expression from Magnolia obovata in activated macrophages. Planta Med. 200;66:469-471.

101) Chen F, Wang T, Wu YF, et al. Honokiol a potent chemotherapy candidate for human colorectal carcinoma. World J Gastroenterol. 2004;10:3459-3463.

102) Bai X, Cerimele F, Ushio-Fukai M, et al. Honokiol, a small molecular weight natural product, inhibits tumor growth in vivo. J Biol Chem. 2000;278:35501-35507.

103) Zhang L, Rui YC, Yang PY, et al. Inhibitory effects of ginkgo biloba extract on vascular endothelial growth factor in rat aortic endothelial cells. Acta Pharmacol Sin. 2002;23:919-923.

104) De Feudis FV, Papadopoulos V, Drieu K. Ginkgo biloba extracts and cancer: a research area in its infancy. Fundam Clin Pharmacol. 2003;17:405-417.

105) Iwanowycz S, Wang J, Hodge J, et al. Emodin Inhibits Breast Cancer Growth by Blocking the Tumor-Promoting Feedforward Loop between Cancer Cells and Macrophages. Mol Cancer Ther. 2016 Aug;15(8):1931-42.

106) Zhang J, Wang L, Zhang Y, et al. Chemopreventive effect of Korean Angelica root extraxct on TRAMP carcinogenesis and integrative “omic” profiling of affected neuroendocrine carcinomas. Mol Carcinog. 2014 Oct 12 (Epub ahead of print).

107) Zhang J, Li J, Song H, et al. Hydroxysafflor yellow A suppresses angiogenesis of hepatocellular carcinoma through inhibition of p38 MAPK phosphorylation. Biomed Pharmacother. 2019 Jan;109:806-814.

108) Yang F, Li J, Zhu J, et al. Hydroxysafflor yellow A inhibits angiogenesis of hepatocellular carcinoma via blocking ERK/MAPK and NF-κB signaling pathway in H22 tumor-bearing mice. Eur J Pharmacol. 2015 May 5;754:105-14.

821 views0 comments


Commenting has been turned off.
bottom of page