Angiogenesis, Inflammation & Therapeutics | Impact 0.1 (CiteScore) | Online ISSN  2207-872X
REVIEWS   (Open Access)

Phytochemicals with Direct and/or Indirect Anti-angiogenic Properties Against Various Cancer Types Focusing on Their Mechanism of Action

Ibrahim Al-deeb1,2,3, Julia Joseph1, Amin Malik Shah Abdul Majid2, Nozlena Abdul Samad1

+ Author Affiliations

Journal of Angiotherapy 5(1) 226-233 https://doi.org/10.25163/angiotherapy.51212406111121

Submitted: 06 May 2021  Revised: 28 October 2021  Published: 11 November 2021 

Abstract


Cancer remains the second leading cause of death despite continuous efforts that have been spent on cancer treatment. The escalating cases are due to several challenges in cancer therapy, including the non-selective toxicity of chemotherapies and chemoresistance. Therefore, alternative strategies are developed to prevent, reverse or delay the carcinogenesis process. One of these strategies is to inhibit or control angiogenesis, a process of the formation of new blood vessels from a pre-existing vessel. Several clinically approved anti-angiogenics showed evidence to suppress tumour growth and aggressiveness. However, some patients could not respond well to these therapies as expected due to the relapse of cancer or their side effects. Nowadays, phytochemicals have been receiving special attention in developing new molecules that can inhibit angiogenesis. This application is due to their pleiotropic behaviours, where phytochemicals could have multiple mechanisms affecting multiple signalling pathways, such as cell growth, apoptosis, and cell survival, in addition to their perceived safety over synthetic compounds. In this article, some phytochemicals are highlighted by referring to their mechanisms of action as anti-angiogenics. Based on the literature, most phytochemicals indirectly exert their anti-angiogenic effect; therefore, more attention should be pointed to the direct anti-angiogenic effect. In summary, this review described angiogenesis targets for some phytochemicals, providing useful information for developing new selective anti-angiogenic therapy that can be used in combination with other chemotherapeutics or as chemopreventive agents.

Keywords: cancer, phytochemicals, direct anti-angiogenesis, indirect anti-angiogenesis

References


Aggarwal, B. B. and Shishodia, S. (2006) ‘Molecular targets of dietary agents for prevention and therapy of cancer’, Biochemical pharmacology. Elsevier, 71(10), pp. 1397–1421.

Albini, A. et al. (2012) ‘Cancer prevention by targeting angiogenesis’, Nature reviews Clinical oncology. Nature Publishing Group, 9(9), p. 498.

Banudevi, S., Swaminathan, S. and Maheswari, K. U. (2015) ‘Pleiotropic role of dietary phytochemicals in cancer: emerging perspectives for combinational therapy’, Nutrition and cancer. Taylor & Francis, 67(7), pp. 1021–1048.

Batra, P. and Sharma, A. K. (2013) ‘Anti-cancer potential of flavonoids: recent trends and future perspectives. 3 Biotech, 3 (6), 439–459’.

Beh, H.-K. et al. (2012) ‘Anti-angiogenic activity of Morinda citrifolia extracts and its chemical constituents’, Natural product research. Taylor & Francis, 26(16), pp. 1492–1497.

Bergers, G. and Benjamin, L. E. (2003) ‘Angiogenesis: tumorigenesis and the angiogenic switch’, Nature reviews cancer. Nature Publishing Group, 3(6), p. 401.

Bolhassani, A. (2015) ‘Cancer chemoprevention by natural carotenoids as an efficient strategy’, Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). Bentham Science Publishers, 15(8), pp. 1026–1031.

Carmeliet, P. and Jain, R. K. (2000) ‘Angiogenesis in cancer and other diseases’, Nature, 407(6801), pp. 249–257. doi: 10.1038/35025220.

Cavada, B. S. et al. (2001) ‘Revisiting proteus: do minor changes in lectin structure matter in biological activity? Lessons from and potential biotechnological uses of the Diocleinae subtribe lectins’, Current Protein and Peptide Science. Bentham Science Publishers, 2(2), pp. 123–135.

Chen, S. et al. (2016) ‘A systematic study of the dissolution and relative bioavailability of four ginsenosides in the form of ultrafine granular powder, common powder and traditional pieces of Panax quinquefolius L, in vitro and in beagles’, Journal of ethnopharmacology. Elsevier, 185, pp. 9–16.

Chintharlapalli, S. et al. (2007) ‘Betulinic acid inhibits prostate cancer growth through inhibition of specificity protein transcription factors’, Cancer research. AACR, 67(6), pp. 2816–2823.

Cichewicz, R. H. and Kouzi, S. A. (2004) ‘Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection’, Medicinal research reviews. Wiley Online Library, 24(1), pp. 90–114.

Costa, C., Incio, J. and Soares, R. (2007) ‘Angiogenesis and chronic inflammation: cause or consequence?’, Angiogenesis. Springer, 10(3), pp. 149–166.

Duthie, S. J. et al. (2006) ‘The effects of cranberry juice consumption on antioxidant status and biomarkers relating to heart disease and cancer in healthy human volunteers’, European journal of nutrition. Springer, 45(2), pp. 113–122.

Engelmann, C. et al. (2002) ‘Apigenin–strong cytostatic and anti-angiogenic action in vitro contrasted by lack of efficacy in vivo’, Phytomedicine. Elsevier, 9(6), pp. 489–495.

Fagiani, E. and Christofori, G. (2013) ‘Angiopoietins in angiogenesis’, Cancer letters. Elsevier, 328(1), pp. 18–26.

Ferrara, N. (2010) ‘Pathways mediating VEGF-independent tumor angiogenesis’, Cytokine & growth factor reviews. Elsevier, 21(1), pp. 21–26.

Fidler, M. M., Soerjomataram, I. and Bray, F. (2016) ‘A global view on cancer incidence and national levels of the human development index’, International journal of cancer. Wiley Online Library, 139(11), pp. 2436–2446.

Fulda, S. (2008) ‘Betulinic acid for cancer treatment and prevention’, International journal of molecular sciences. Molecular Diversity Preservation International, 9(6), pp. 1096–1107.

Funahashi, Y. et al. (2008) ‘A notch1 ectodomain construct inhibits endothelial notch signaling, tumor growth, and angiogenesis’, Cancer research. AACR, 68(12), pp. 4727–4735.

Giannoni, E. et al. (2010) ‘Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness’, Cancer research. AACR, 70(17), pp. 6945–6956.

Goel, A., Kunnumakkara, A. B. and Aggarwal, B. B. (2008) ‘Curcumin as “Curecumin”: from kitchen to clinic’, Biochemical pharmacology. Elsevier, 75(4), pp. 787–809.

González-Vallinas, M. et al. (2013) ‘Dietary phytochemicals in cancer prevention and therapy: a complementary approach with promising perspectives’, Nutrition reviews. Oxford University Press Oxford, UK, 71(9), pp. 585–599.

Hanahan, D. and Weinberg, R. A. (2017) ‘Hallmarks of Cancer: The Next Generation’, Cell, 144, pp. 646–674. doi: 10.1016/j.cell.2011.02.013.

Harikumar, K. B. et al. (2010) ‘Resveratrol, a multitargeted agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer’, International journal of cancer. Wiley Online Library, 127(2), pp. 257–268.

Hu, B. et al. (2016) ‘Preventive and therapeutic effects of Chinese herbal compounds against hepatocellular carcinoma’, Molecules. Multidisciplinary Digital Publishing Institute, 21(2), p. 142.

Huang, C. et al. (2016) ‘Chrysin, Abundant in Morinda citrifolia Fruit Water–EtOAc Extracts, Combined with Apigenin Synergistically Induced Apoptosis and Inhibited Migration in Human Breast and Liver Cancer Cells’, Journal of agricultural and food chemistry. ACS Publications, 64(21), pp. 4235–4245.

Jackson, J. R. et al. (1997) ‘The codependence of angiogenesis and chronic inflammation.’, The FASEB Journal, 11(6), pp. 457–465.

Jemal, A. et al. (2011) ‘Global cancer statistics’, CA Cancer J Clin. 2011/02/08. Surveillance Research, American Cancer Society, Atlanta, GA, USA. ahmedin.jemal@cancer.org, 61, pp. 69–90. doi: 10.3322/caac.20107.

Jung, Y. D. et al. (2001) ‘EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells’, British journal of cancer. Nature Publishing Group, 84(6), p. 844.

Kang, S. Y. et al. (1998) ‘Hepatoprotective activity of scopoletin, a constituent ofSolanum lyratum’, Archives of pharmacal research. Springer, 21(6), p. 718.

Kerbel, R. and Folkman, J. (2002) ‘Clinical translation of angiogenesis inhibitors’, Nature Reviews Cancer, 2, p. 727.

Kerbel, R. S. (2008) ‘Tumor angiogenesis’, New England Journal of Medicine. Mass Medical Soc, 358(19), pp. 2039–2049.

Kevil, C. G. et al. (2004) ‘Intercellular adhesion molecule-1 (ICAM-1) regulates endothelial cell motility through a nitric oxide-dependent pathway’, Journal of Biological Chemistry. ASBMB, 279(18), pp. 19230–19238.

Key, T. J. et al. (2004) ‘Diet, nutrition and the prevention of cancer’, Public health nutrition. Cambridge University Press, 7(1a), pp. 187–200.

Khan, N., Afaq, F. and Mukhtar, H. (2008) ‘Cancer chemoprevention through dietary antioxidants: progress and promise’, Antioxidants & redox signaling. Mary Ann Liebert, Inc. 2 Madison Avenue Larchmont, NY 10538 USA, 10(3), pp. 475–510.

Khuda-Bukhsh, A. R., Das, S. and Saha, S. K. (2014) ‘Molecular approaches toward targeted cancer prevention with some food plants and their products: inflammatory and other signal pathways’, Nutrition and cancer. Taylor & Francis, 66(2), pp. 194–205.

Kim, H.-Y., Kim, O.-H. and Sung, M.-K. (2003) ‘Effects of phenol-depleted and phenol-rich diets on blood markers of oxidative stress, and urinary excretion of quercetin and kaempferol in healthy volunteers’, Journal of the American College of Nutrition. Taylor & Francis, 22(3), pp. 217–223.

Kim, M. H. (2003) ‘Flavonoids inhibit VEGF/bFGF-induced angiogenesis in vitro by inhibiting the matrix-degrading proteases’, Journal of cellular biochemistry. Wiley Online Library, 89(3), pp. 529–538.

Kiran, M. S. et al. (2008) ‘Modulation of angiogenic factors by ursolic acid’, Biochemical and biophysical research communications. Elsevier, 371(3), pp. 556–560.

Koskensalo, S. et al. (2011) ‘MMP-7 as a prognostic marker in colorectal cancer’, Tumor Biology, 32(2), pp. 259–264. doi: 10.1007/s13277-010-0080-2.

Koukourakis, M. I. et al. (2001) ‘Hypoxia inducible factor (HIF-1a and HIF-2a) expression in early esophageal cancer and response to photodynamic therapy and radiotherapy’, Cancer research. AACR, 61(5), pp. 1830–1832.

Ku, C.-M. and Lin, J.-Y. (2013) ‘Anti-inflammatory effects of 27 selected terpenoid compounds tested through modulating Th1/Th2 cytokine secretion profiles using murine primary splenocytes’, Food chemistry. Elsevier, 141(2), pp. 1104–1113.

Kudryavtseva, A. et al. (2016) ‘Effects of Abies sibirica terpenes on cancer-and aging-associated pathways in human cells’, Oncotarget. Impact Journals, LLC, 7(50), p. 83744.

Landis-Piwowar, K. R. and Iyer, N. R. (2015) ‘Cancer chemoprevention: current state of the art. Cancer Growth Metastasis. 2014; 7: 19–25’, Cite this article: Buriani A. The Systems Biology Oriented, Holistic Vision of Personalized Medicine and The Emerging Concept of Proactive Herbal Medicine. JJ Intern Medicine.

Li, N. et al. (2015) ‘Natural flavonoids function as chemopreventive agents from Gancao (Glycyrrhiza inflata Batal)’, Journal of Functional Foods. Elsevier, 19, pp. 563–574.

Lin, C.-C. et al. (2010) ‘Antiangiogenic potential of three triterpenic acids in human liver cancer cells’, Journal of agricultural and food chemistry. ACS Publications, 59(2), pp. 755–762.

Lin, J. N. et al. (2013) ‘Effects of triterpenoid from Psidium guajava leaves ursolic acid on proliferation, differentiation of 3T3-L1 preadipocyte and insulin resistance’, Zhong yao cai= Zhongyaocai= Journal of Chinese medicinal materials, 36(8), pp. 1293–1297.

Liobikas, J. et al. (2011) ‘Uncoupling and antioxidant effects of ursolic acid in isolated rat heart mitochondria’, Journal of natural products. ACS Publications, 74(7), pp. 1640–1644.

Liu, L.-Z. et al. (2005) ‘Apigenin inhibits expression of vascular endothelial growth factor and angiogenesis in human lung cancer cells: implication of chemoprevention of lung cancer’, Molecular pharmacology. ASPET, 68(3), pp. 635–643.

Liu, R. H. (2004) ‘Potential synergy of phytochemicals in cancer prevention: mechanism of action’, The Journal of nutrition. Oxford University Press, 134(12), pp. 3479S-3485S.

Liu, X.-L. et al. (2001) ‘Effect of scopoletin on PC3 cell proliferation and apoptosis.’, Acta Pharmacologica Sinica, 22(10), pp. 929–933.

Liu, Z. 1 et al. (2013) ‘Could plant lectins become promising anti-tumour drugs for causing autophagic cell death?’, Cell proliferation. Wiley Online Library, 46(5), pp. 509–515.

Lluria-Prevatt, M. and Alberts, D. S. (2008) ‘Skin cancer prevention’, in Fundamentals of Cancer Prevention. Springer, pp. 239–289.

Löhnert, A. et al. (2014) ‘Ethnopharmacology and phytotherapy’, in Biodiversity, Natural Products And Cancer Treatment. World Scientific, pp. 251–287.

Mailhos, C. et al. (2001) ‘Delta4, an endothelial specific notch ligand expressed at sites of physiological and tumor angiogenesis’, Differentiation. Elsevier, 69(2–3), pp. 135–144.

McKay, D. L. and Blumberg, J. B. (2006) ‘A review of the bioactivity and potential health benefits of chamomile tea (Matricaria recutita L.)’, Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. Wiley Online Library, 20(7), pp. 519–530.

Mertens-Talcott, S. U. et al. (2013) ‘Betulinic acid decreases ER-negative breast cancer cell growth in vitro and in vivo: Role of Sp transcription factors and microRNA-27a: ZBTB10’, Molecular carcinogenesis. Wiley Online Library, 52(8), pp. 591–602.

Mukhtar, E. et al. (2012) ‘Apoptosis and autophagy induction as mechanism of cancer prevention by naturally occurring dietary agents’, Current drug targets. Bentham Science Publishers, 13(14), pp. 1831–1841.

Nascimento, K. S. et al. (2016) ‘Purification of a thermostable antinociceptive lectin isolated from Andira anthelmia’, Journal of Molecular Recognition. Wiley Online Library, 29(6), pp. 248–252.

Nyberg, P., Xie, L. and Kalluri, R. (2005) ‘Endogenous inhibitors of angiogenesis’, Cancer research. AACR, 65(10), pp. 3967–3979.

Oliveira, E. J. et al. (2001) ‘Intracellular calcium mobilization as a target for the spasmolytic action of scopoletin’, Planta medica. © Georg Thieme Verlag Stuttgart· New York, 67(07), pp. 605–608.

Prasad, S., Tyagi, A. K. and Aggarwal, B. B. (2014) ‘Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice’, Cancer research and treatment: official journal of Korean Cancer Association. Korean Cancer Association, 46(1), p. 2.

Pugh, C. W. and Ratcliffe, P. J. (2003) ‘Regulation of angiogenesis by hypoxia: role of the HIF system’, Nature medicine. Nature Publishing Group, 9(6), p. 677.

Ridgway, J. et al. (2006) ‘Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis’, Nature. Nature Publishing Group, 444(7122), p. 1083.

Rufino-Palomares, E. E. et al. (2015) ‘Anti-cancer and anti-angiogenic properties of various natural pentacyclic tri-terpenoids and some of their chemical derivatives’, Current Organic Chemistry. Bentham Science Publishers, 19(10), pp. 919–947.

Shankar, E. et al. (2017) ‘Plant flavone apigenin: an emerging anticancer agent’, Current pharmacology reports. Springer, 3(6), pp. 423–446.

Shanmugam, M. K. et al. (2013) ‘Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies’, Biochemical pharmacology. Elsevier, 85(11), pp. 1579–1587.

Shaw, C. et al. (2003) ‘Antioxidant properties of scopoletin isolated from Sinomonium acutum’, Phytotherapy Research. Wiley Online Library, 17(7), pp. 823–825.

Shivamadhu, M. C. et al. (2017) ‘Anti-cancer and anti-angiogenic effects of partially purified lectin from Praecitrullus fistulosus fruit on in vitro and in vivo model’, Biomedicine & Pharmacotherapy. Elsevier, 96, pp. 1299–1309.

Shukla, S. and Gupta, S. (2010) ‘Apigenin: a promising molecule for cancer prevention’, Pharmaceutical research. Springer, 27(6), pp. 962–978.

Sun, H. et al. (2006) ‘Structure-activity relationships of oleanane-and ursane-type triterpenoids’, Botanical Studies. ??????????, 47(4), pp. 339–368.

Sung, B., Chung, H. Y. and Kim, N. D. (2016) ‘Role of apigenin in cancer prevention via the induction of apoptosis and autophagy’, Journal of cancer prevention. Korean Society of Cancer Prevention, 21(4), p. 216.

Tabana, Y. M. et al. (2016) ‘Scopoletin, an active principle of tree tobacco (Nicotiana glauca) inhibits human tumor vascularization in xenograft models and modulates ERK1, VEGF-A, and FGF-2 in computer model’, Microvascular research. Elsevier, 107, pp. 17–33.

Thani, W. et al. (2010) ‘Anti-proliferative and antioxidative activities of Thai noni/Yor (Morinda citrifolia Linn.) leaf extract’, Southeast Asian J Trop Med Public Health, 41(2), pp. 482–489.

Vasudev, N. S. and Reynolds, A. R. (2014) ‘Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions’, Angiogenesis, 17, pp. 471–494.

Vlodavsky, I. and Friedmann, Y. (2001) ‘Molecular properties and involvement of heparanase in cancer metastasis and angiogenesis’, The Journal of clinical investigation. Am Soc Clin Investig, 108(3), pp. 341–347.

Wälchli, T. et al. (2015) ‘Wiring the vascular network with neural cues: a CNS perspective’, Neuron. Elsevier, 87(2), pp. 271–296.

Wang, C.-Z., Anderson, S. and Yuan, C.-S. (2016) ‘Phytochemistry and anticancer potential of notoginseng’, The American journal of Chinese medicine. World Scientific, 44(01), pp. 23–34.

Yoshiji, H., Harris, S. R. and Thorgeirsson, U. P. (1997) ‘Vascular endothelial growth factor is essential for initial but not continued in vivo growth of human breast carcinoma cells’, Cancer Research, 57, pp. 3924–3928.

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