Probing into Therapeutic Anti-cancer Potential of Apigenin: Recent Trends and Future Directions

Author(s): Ajay Sharma, Abdul Ghani, Katrin Sak, Hardeep S. Tuli*, Anil K. Sharma, William N. Setzer, Sanjeev Sharma, Amit K. Das

Journal Name: Recent Patents on Inflammation & Allergy Drug Discovery
Continued as Recent Advances in Inflammation & Allergy Drug Discovery

Volume 13 , Issue 2 , 2019


Background: Natural products represent a therapeutic option for the treatment of inflammation- associated diseases. Flavonoids which are one of the special categories of such natural products, have previously shown promising therapeutic potential.

Objectives: The current review discusses the synthetic preview and anti-inflammatory potential of apigenin along with the underlying molecular mechanism in chronic human diseases especially cancer. In addition, the relevant patents on the therapeutic potential of apigenin have also been mentioned.

Methods: A literature search was carried out using PubMed/Science, Google Scholar, etc. which was further expended by the different combination of keywords: apigenin, inflammation, mechanism, therapeutic potential, cancer, etc. Patent information was retrieved by searching the key terms: apigenin, inflammation, therapeutic potential from various databanks including Espacenet, Google Patents, Free Patents Online and Mendeley of WIPO, USPTO, SIPO, JPO, KIPO and EPO databases.

Results: A total of 76 references have been found relevant with the theme of the manuscript. These citations have described recent ongoing advances in the area of inflammation and cancer with respect to apigenin.

Conclusion: Studies related to the anti-inflammatory and anticancer potential of apigenin have been explored through this review article. Moreover, the patent analysis of apigenin has further strengthened its therapeutic role. Probing into the therapeutic properties of apigenin, further adds value to this molecule in terms of its downregulation of major inflammatory and cancer-associated signaling pathways. The article would simultaneously assist the scientific community to precisely understand the role of apigenin and design novel anti-cancer therapies.

Keywords: Apigenin, cancer, derivatives, flavonoids, inflammation, patents, synthetic preview, therapeutic.

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136(5): E359-86.
Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn Rev 2014; 8(16): 122-46.
Kashyap D, Sharma A, Tuli HS, Sak K, Garg VK, Buttar HS, et al. Apigenin: A natural bioactive flavone-type molecule with promising therapeutic function. J Funct Foods 2018; 48: 457-71.
Bhagwat S, Haytowitz DB, Holden JM. USDA Database for the flavonoid content of selected foods. U.S. Dep Argiculture 2011; pp. 1-156.
Ali F. Rahul, Naz F, Jyoti S, Siddique YH. Health functionality of apigenin: A review. Int J Food Prop 2017; 20: 1197-238.
Sharma A, Sharma P, Tuli HS, Sharma AK. Phytochemical and Pharmacological Properties of Flavonols. In: ELS. Chichester, UK: John Wiley & Sons Ltd 2018; pp. 1-12.
Lee H, Kim BG, Kim M, Ahn JH. Biosynthesis of two flavones, Apegenin and genkwanin, in Escherichia coli. J Microbiol Biotechnol 2015; 25: 1442-8.
Marin L, Gutierrez-del-Rio I, Yague P, Manteca A, Villar CJ, Lombo F. De novo biosynthesis of apigenin, luteolin, and eriodictyol in the actinomycete Streptomyces albus and production improvement by feeding and spore conditioning. Front Microbiol 2017; 8: 921.
Hutchins WA, Wheeler TS. 17. Chalkones: A new synthesis of chrysin, apigenin, and luteolin. J Chem Soc 1939; 91
Wang Q, Cui W, Liu M, Zhang J, Liao RQ, Liao XL, et al. An improved synthesis of apigenin. J Chem Res 2015; 39: 67-9.
Kumar H, Kawai T, Akira S. Pathogen recognition in the innate immune response. Biochem J 2009; 420(1): 1-6.
Anand P, Kunnumakara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, et al. Cancer is a preventable disease that requires major lifestyle changes. Pharm Res 2008; 25(9): 2097-116.
Yan X, Qi M, Li P, Zhan Y, Shao H. Apigenin in cancer therapy: Anti-cancer effects and mechanisms of action. Cell Biosci 2017; 7(1): 50.
Zhao G, Han X, Cheng W, et al. Apigenin inhibits proliferation and invasion, and induces apoptosis and cell cycle arrest in human melanoma cells. Oncol Rep 2017; 37(4): 2277-85.
Garcaa-Lafuente A, Guillamón E, Villares A, Rostagno MA, Martínez JA. Flavonoids as anti-inflammatory agents: Implications in cancer and cardiovascular disease. Inflamm Res 2009; 58(9): 537-52.
Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 20(6917): 860.
Kuper H, Adami HO, Trichopoulos D. Infections as a major preventable cause of human cancer. J Intern Med 2000; 248(3): 171-83.
Ernst PB, Gold BD. The disease spectrum of Helicobacter pylori: The immunopathogenesis of gastroduodenal ulcer and gastric cancer. Annu Rev Microbiol 2000; 54(1): 615-40.
Hudson JD, Shoaibi MA, Maestro R, Carnero A, Hannon GJ, Beach DH. A proinflammatory cytokine inhibits p53 tumor suppressor activity. J Exp Med 1999; 190(10): 1375-82.
Shukla S, Gupta S. Apigenin: A promising molecule for cancer prevention. Pharm Res 2010; 27(6): 962-78.
Hu XW, Meng D, Fang J. Apigenin inhibited migration and invasion of human ovarian cancer A2780 cells through focal adhesion kinase. Carcinogenesis 2008; 29(12): 2369-76.
Adebamowo CA, Cho E, Sampson L, Katan MB, Spiegelman D, Willett WC, et al. Dietary flavonols and flavonol‐rich foods intake and the risk of breast cancer. Int J Cancer 2005; 114(4): 628-33.
Wang YC, Huang KM. In vitro anti-inflammatory effect of apigenin in the Helicobacter pylori-infected gastric adenocarcinoma cells. Food Chem Toxicol 2013; 53: 376-83.
Sung B, Chung HY, Kim ND. Role of apigenin in cancer prevention via the induction of apoptosis and autophagy. J Cancer Prev 2016; 21(4): 216.
Ginwala R, Bhavsar R, Chigbu De Gaulle I, Jain P, Khan ZK. Potential role of flavonoids in treating chronic inflammatory diseases with a special focus on the anti-inflammatory activity of apigenin. Antioxidants 2019; 8: 35.
Sharma H, Kanwal R, Bhaskaran N, Gupta S. Plant flavone apigenin binds to nucleic acid bases and reduces oxidative DNA damage in prostate epithelial cells. PLoS One 2014; 9(3)e91588
Zhang X, Wang G, Gurley EC, Zhou H. Flavonoid apigenin inhibits lipopolysaccharide-induced inflammatory response through multiple mechanisms in macrophages. PLoS One 2014; 9(9)e107072
Yadav P, Jaswal V, Sharma A, Kashyap D, Tuli HS, Garg VK, et al. Celastrol as a pentacyclic triterpenoid with chemopreventive properties. Pharm Pat Anal 2018; 7: 155-67.
Kashyap D, Sharma A, Tuli HS, Punia S, Sharma AK. Ursolic acid and oleanolic acid: Pentacyclic terpenoids with promising anti-inflammatory activities. Recent Pat Inflamm Allergy Drug Discov 2016; 10: 1-13.
Sharma A, Kashyap D, Sak K, Tuli HS, Sharma AK. Therapeutic charm of quercetin and its derivatives: A review of research and patents. Pharm Pat Anal 2018; 7: 15-32.
Chakrawarti L, Agrawal R, Dang S, Gupta S, Gabrani R. Therapeutic effects of EGCG: A patent review. Expert Opin Ther Pat 2016; 26: 907-16.
Di Martino RMC, Luppi B, Bisi A, Gobbi S, Rampa A, Abruzzo A, et al. Recent progress on curcumin-based therapeutics: A patent review (2012-2016). Part I: Curcumin. Expert Opin Ther Pat 2017; 27: 579-90.
Uivarosi V, Munteanu AC, Sharma A, Tuli HS. Metal Complexation and Patent Studies of Flavonoid. In: Tuli HS, Ed. Current Aspects of Flavonoids: Their Role in Cancer Treatment. Singapore: Springer 2019; pp. 39-89.
Baek BE, Hoon KJ, Nam PJ, Hyun PS, Su JB. Method for improving anti-cancer effect of apigenin by irradiation and pharmaceutical composition for treating or preventing cancer comprising irradiated apigenin. KR20160132185 (2016).
Xiaoli Z. Granules for assisting in radiation resistance in tumor interventional therapy CN106177899 (2016).
Birbara PJ, Cummings JS, Ginter K, Raman K. Polyphenol/ flavonoid compositions and methods of formulating oral hygienic products. US20170718401 (2017).
Cheol-Woo K, Young JJ. Pharmaceutical compositions for preventing or treating lung cancer comprising apigenin, curcumin, and honokiol as active ingredients. KR101803000B1 (2017).
Cheng Y, Tao S. Applications of apigenin for preparation of medicines inhibiting liver cancer epithelial-mesenchymal transition. CN106377522 (2017).
Lihua T. Applications of apigenin in preparation of gastric cancer treatment drugs. CN107837264 (2018).
Lihua T. Application of apigenin in preparation of drugs used for treating rectal cancer. CN107865856 (2018).
Lihua T. Application of apigenin in preparation of drugs used for treating pancreas cancer. CN107837251 (2018).
Lihua T. Application of apigenin to prepare medicine for treating cervical cancer. CN107865860 (2018).
Lihua T. Application of Apigenin to prepare medicine for treating tongue cancer. CN107865861 (2018).
Lihua T. Application of apigenin to preparation of drugs capable of resisting lung cancer metastasis. CN107865857 (2018).
Lihua T. Application of apigenin to prepare medicine for treating ileocecal cancer. CN107865863 (2018).
Lihua T. Application of apigenin in preparation of drugs used for treating nasopharyngeal carcinoma CN107865852 (2018).
Zuohuan M, Jiming J, Zongquan W, et al. Flavonoid derivatives and a preparation method and uses. CN108017608 (2018).
Cheng Y, Guang Y, Honggang Z, Tao S. Flavonoids and their application in anticancer drugs. CN108276373 (2018).
Lihua T. Application of apigenin to prepare medicine for treating rhinitis. CN107865862 (2018).
Lihua T. Application of apigenin to preparation of drugs capable of resisting aseptic inflammations. CN107865858 (2018).
Lihua T. Application of apigenin in preparation of drugs used for treating breast cancer. CN107865855 (2018).
Lihua T. Use of Apigenin in preparation of drugs for treating endometrial cancer. CN107865839 (2018).
Hua X. Application of frangrant ainsliaea herb extract to antibacterial and anti-inflammatory medicine. CN108014157 (2018).
Jian L, Miaomiao T, Zhuyi Z, Zhong Z. Application of apigenin in inhibition of activation of Wnt/beta-catenin signal channel of colon cancer cell. CN107397741 (2017).
Lihua T. Use of apigenin in preparation of drug for treating laryngeal cancer. CN107865838 (2018).
Lihua T. Application of apigenin in preparation of cholangiocarcinoma treatment drugs. CN107854459 (2018).
Cheol-Woo K, Young JJ. Pharmaceutical composition comprising apigenin, curcumin, and honokiol as active ingredients for preventing or treating lung cancer. WO2018043989 (2018).
Lihua T. Application of apigenin to preparation of antidepressant drugs. CN107865853 (2018).
Lihua T. Application of apigenin in preparation of drug for treating or preventing acute heart failure. CN107913268 (2018).
Lihua T. Application of Apigenin in preparation of acute gout treatment drugs. CN107854460 (2018).
Lihua T. Application of Apigenin in preparation of erythrocyte increasing drugs. CN107854458 (2018).
Gates MA, Tworoger SS, Hecht JL, De Vivo I, Rosner B, Hankinson SE. A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer. Int J Cancer 2007; 121: 2225-32.
[63] Identifier: NCT03139227
[64] Identifier: NCT03526081
[65] Identifier: NCT00609310.
Zhou Y, Wang Z, Xu L, Tang H, Wang D, Meng Q. 39 Studies on the antidiabetic activity of apigenin in mice with streptozotocin-induced diabetes. J Investig Med 2016; 64: A14.
Kanerva A, Raki M, Ranki T, Särkioja M, Koponen J, Desmond RA, et al. Chlorpromazine and apigenin reduce adenovirus replication and decrease replication associated toxicity. J Gene Med 2007; 9(1): 3-9.
Lakshmanan A, Scarberry D, Green JA, Zhang X, Selmi-Ruby S, Jhiang SM. Modulation of thyroidal radioiodide uptake by oncological pipeline inhibitors and apigenin. Oncotarget 2015; 6(31): 31792.
Banerjee K, Banerjee S, Mandal M. Enhanced chemotherapeutic efficacy of apigenin liposomes in colorectal cancer based on flavone-membrane interactions. J Colloid Interface Sci 2017; 491: 98-110.
Papay ZE, Balogh E, Zariwala MG, Somavarapu S, Antal I. Drug delivery approaches for apigenin: A review. InStacks NM, Eds, Apigenin and Naringenin: Natural Sources, Pharmacology and Role in Cancer Prevention. New York: Nova Science Publishers, Inc., 2015; 1-20.
Alshehri SM, Shakeel F, Ibrahim MA, Elzayat EM, Altamimi M, Mohsin K, et al. Dissolution and bioavailability improvement of bioactive apigenin using solid dispersions prepared by different techniques. Saudi Pharm J 2019; 27(2): 264-73.
Ding SM, Zhang ZH, Song J, Cheng XD, Jiang J, Jia XB. Enhanced bioavailability of apigenin via preparation of a carbon nanopowder solid dispersion. Int J Nanomedicine 2014; 9: 2327-33.
Salehi B, Venditti A, Sharifi-Rad M, Kręgiel D, Sharifi-Rad J, Durazzo A, et al. The therapeutic potential of apigenin. Int J Mol Sci 2019; 20(6): 1305.
Papay ZE, Kallai-Szabo N, Balogh E, Ludanyi K, Klebovich I, Antal I. Controlled release oral delivery of apigenin containing pellets with antioxidant activity. Curr Drug Deliv 2017; 14(1): 145-54.
Das S, Das J, Samadder A, Paul A, Khuda-Bukhsh AR. Efficacy of PLGAloaded apigenin nanoparticles in benzo[a]pyrene and ultraviolet-B induced skin cancer of mice: Mitochondria mediated apoptotic signalling cascades. Food Chem Toxicol 2013; 62: 670-80.
Telange DR, Patil AT, Pethe AM, Fegade H, Anand S, Dave VS. Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential. Eur Pharm Sci 2017; 108: 36-49.

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Article Details

Year: 2019
Published on: 04 December, 2019
Page: [124 - 133]
Pages: 10
DOI: 10.2174/1872213X13666190816160240

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