Advances in Clinical and Experimental Medicine
2017, vol. 26, nr 7, October, p. 1143–1146
doi: 10.17219/acem/41978
Publication type: review
Language: English
Download citation:
Insights into novel anticancer applications for apigenin
1 Department of Pharmacognosy, Wroclaw Medical University, Poland
2 Students’ Pharmacognosy Society, Wroclaw Medical University, Poland
3 Students’ Industrial Pharmacy Society, Wroclaw Medical University, Poland
4 Department of Industrial Pharmacy, Wroclaw Medical University, Poland
Abstract
Flavonoids, naturally occuring derivatives of 2-phenyl-benzo-γ-pyrone, are widespread in plants as coloring substances. Apigenin (4’,5,7,-trihydroxyflavone (5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one), molecular formula C₁₅H₁₀O⁵, is a flavonoid present in many fruits and vegetables, primarily in citrus fruits, apples, parsley and celery leaves. It is also found in some medicinal plants, including chamomile flowers, thyme, oregano, peppermint, lemon balm and yarrow, as a 7-O-glycoside with anti-inflammatory and antioxidant activity. In recent years it has attracted a great deal of interest as a bioactive substance reported to have anticancer properties. According to recent literature data, apigenin is able to reduce cancer cell glucose uptake, inhibit remodeling of the extracellular matrix, inhibit cell adhesion molecules that participate in cancer progression and hinder the development of blood vessels needed by growing tumors. It is reported to protect against a wide variety of cancers. The mechanism of anticancer activity is still under investigation and further research is needed.
Key words
flavonoids, apigenin, anticancer agent, chemoprevention
References (39)
- Lefort ÉC, Blay J. Apigenin and its impact on gastrointestinal cancers. Mol Nutr Food Res. 2013;57:126–144.
- Andersen Ø, Markham KR. Flawonoids: Chemistry, Biochemistry and Applications. New York, NY: Taylor & Francis Group; 2006:219–220.
- Cushnie TPT, Lamb AJ. Recent advances in understanding the antibacterial properties of flavonoids. Int J Antimicrob Agents. 2011;38:99–107.
- García-Lafuente A, Gullamón E, Villares A, Rostagno MA, Martínez JA. Flawonoids as anti-inflammatory agents: Implications in cancer and cardiovascular disease. Inflamm Res. 2009;58:537–552.
- Kawai M, Hirano T, Higa S, et al. Flawonoids and related compounds as anti-allergic substances. Allergol Int. 2007;56:113–123.
- Li AN, Li S, Zhang YJ, Xu XR, Chen YM, Li HB. Resources and biological activities of natural polyphenols. Nutrients. 2014;6:6020–6047.
- Ravishankar D, Rajora AK, Greco F, Osborn HMI. Flawonoids as prospective compounds for anti-cancer therapy. Int J Biochem Cell Biol. 2013;45:2821–2831.
- Lazarevic B, Boezelijn G, Diep LM, et al. Efficacy and safety of short-term genistein intervention in patients with localized prostate cancer prior to radical prostatectomy: A randomized, placebo-controlled, double-blind phase 2 clinical trial. Nutr Cancer. 2011;63:889–898.
- Beesley AH, Stirnweiss A, Ferrari E, et al. Comparative drug screening in NUT midline carcinoma. Br J Cancer. 2014;110:1189–1198.
- Anita S, Manjul PS, Roshan P, Neelam D, Gulzar A. Bio-flavonoid quercetin in oncology. J Pharm Res. 2010;3:2834–2835.
- Yakisich JS, Ohlsson Lindblom I, Siden A, Cruz MH. Rapid inhibition of ongoing DNA synthesis in human glioma tissue by genistein. Oncol Rep. 2009;22:569–574.
- Lin TS, Ruppert AS, Johnson AJ, et al. Phase II study of flavopiridol in relapsed chronic lymphocytic leukemia demonstrating high response rates in genetically high-risk disease. J Clin Oncol. 2009;27:6012–6018.
- Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn Rev. 2014;8:122–146.
- 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.
- Liu HL, Jiang WB, Xie MX. Flawonoids: Recent advances as anticancer drugs. Recent Pat Anticancer Drug Discov. 2010;5:152–164.
- Melstrom LG, Salabat MR, Ding XZ, et al. Apigenin inhibits the GLUT-1 glucose transporter and the phosphoinositide 3-kinase/Akt pathway in human pancreatic cancer cells. Pancreas. 2008:37;426–431.
- Walle T, Ta N, Kawamori T, Wen X, Tsuji PA, Walle UK. Cancer chemopreventive properties of orally bioavailable flavonoids: Methylated versus unmethylated flavones. Biochem Pharmacol. 2007;73:1288–1296.
- Turktekin M, Konac E, Onen HI, Alp E, Yilmaz A, Menevese S. Evaluation of the effects of the flavonoid apigenin on apoptotic pathway gene expression on the colon cancer cell line (HT29). J Med Food. 2011;14:1107–1117.
- King JC, Lu QY, Li G, et al. Evidence for activation of mutated p53 by apigenin in human pancreatic cancer. Biochim Biophys Acta. 2012;1823:539–604.
- Zhong Y, Krisanapun C, Lee SH, et al. Molecular targets of apigenin in colorectal cancer cells: Involvement of p21, NAG-1 and p53. Eur J Cancer. 2010;46:3365–3374.
- Fang J, Zhou Q, Liu LZ, et al. Apigenin inhibits tumor angiogenesis through decreasing HIF-1alpha and VEGF expression. Carcinogenesis. 2007;28:858–864.
- Kim BR, Jeon YK, Nam MJ. A mechanism of apigenin-induced apoptosis in potentially related to anti-angiogenesis and anti-migration in human hepatocellular carcinoma cells. Food Chem Toxicol. 2011;49:1626–1632.
- Melstrom LG, Salabat MR, Ding XZ, et al. Apigenin down-regulates the hypoxia response genes: HIF-1alpha, GLUT-1 and VEGF in human pancreatic cancer cells. J Surg Res. 2011;167:173–181.
- Makrilia N, Kollias A, Manolopoulos L, Syrigos K. Cell adhesion molecules: Role and clinical significance in cancer. Cancer Invest. 2009;27:1023–1037.
- Shukla S, MacLennan GT, Flask CA, et al. Blockade of beta-catenin signaling by plant flavonoid apigenin suppresses prostate carcinogenesis in TRAMP mice. Cancer Res. 2007;67:6925–6935.
- Piantelli M, Rossi C, Iezzi M, et al. Flavonoids inhibit melanoma lung metastasis by impairing tumor cells endothelium interactions. J Cell Physiol. 2006;207:23–29.
- Hehlgans S, Haase M, Cordes N. Signalling via integrins: Implications for cell survival and anticancer strategies. Biochim Biophys Acta. 2007;1775:163–180.
- Hu XW, Meng D, Fang J. Apigenin inhibited imgration and invasion of human ovarian cancer A2780 cells through focal adhesion kinase. Carcinogenesis. 2008;29:2369–2376.
- Franzen CA, Amargo E, Todorovic V, et al. The chemopreventive bioflavonoid apigenin inhibits prostate cancer cell motility through the focal adhesion kinase/Src signaling mechanism. Cancer Prev Res. 2009;2:830–841.
- Matsusue R, Kubo H, Hisamori S, et al. Hepatic stellate cells promote liver metastasis of colon cancer cells by the action of SDF-1/CXCR4 axis. Ann Surg Oncol. 2009;16:2645–2653.
- Koshiba T, Hosotani R, Miyamoto Y, et al. Expression of the stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: A possible role for tumor progression. Clin Cancer Res. 2010;6:3530–3535.
- Mongan JP, Fadul CE, Cole BF, et al. Brain metastases from colorectal cancer: Risk factors, incidence and the possible role of chemokines. Clin Colorectal Cancer. 2009;8:100–105.
- Ottaiano A, Franco R, Aiello Talamanca A, et al. Overexpression of both CXC chemokine receptor 4 and vascular endothelial growth factor proteins predicts early distant relapse in stage II-III colorectal cancer patients. Clin Cancer Res. 2006:12;2795–2803.
- Luker KE, Lewin SA, Mihalko LA, et al. Scavenging of CXCL12 by CXCR7 promotes tumor growth and metastasis of CSCR4-positive breast cancer cells. Oncogene. 2012;31:4750–4758.
- Liu Z, Christensson M, Forslow A, De Meester I, Sundgvist KG. A CD26-controlled cell surface cascade for regulation of T cell motility and chemokine signals. J Immunol. 2009;183:3626–3624.
- Lefort EC, Blay J. The dietary flavonoid apigenin enhances the activities of the anti-metastatic protein CD26 on human colon carcinoma cells. Clin Exp Metastasis. 2011;28:337–349.
- Cheung ZH, Leung MC, Yip HK, Wu W, Siu FK, So KF. A neuroprotective herbal mixture inhibits caspase-3-independent apoptosis in retinal ganglion cells. Cell Mol Neurobiol. 2008;28:137–155.
- Shukla S, Gupta S. Apigenin: A promising molecule for cancer prevention. Pharm Res. 2010;27:962–978.
- Isoda H, Motojima H, Onaga S, Samet I, Villareal MO, Han J. Analysis of the erythroid differentiation effect of flavonoid apigenin on K562 human chronic leukemia cells. Chem Biol Interact. 2014;220:269–277.