Free‑B‑Ring flavonoids as potential lead compounds for colon cancer therapy

Ibrahim,Ahmed; Sobeh,Mohamed; Ismail,Aya; Alaa,Ahmed; Sheashaa,Hussein; Sobh,Mohamed; Badria,Farid

doi:10.3892/mco.2014.278

Free‑B‑Ring flavonoids as potential lead compounds for colon cancer therapy

Authors:
- Ahmed Ibrahim
- Mohamed Sobeh
- Aya Ismail
- Ahmed Alaa
- Hussein Sheashaa
- Mohamed Sobh
- Farid Badria
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Affiliations: Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt, Medical Experimental Research Center, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt, Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
Published online on: April 16, 2014 https://doi.org/10.3892/mco.2014.278
Pages: 581-585

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Abstract

Although flavonoids have been identified as a versatile source of anticancer agents, to the best of our knowledge, no study has yet investigated their anticolon cancer activity in depth. Therefore, the aim of this study was to investigate the association between the structural characteristics of flavonoids and their anticolon cancer activity in the Caco‑2 human colon cancer cell line. Our findings demonstrated that the hydroxylation of C5 and C7 in ring A significantly enhanced the anticolon cancer activity of flavonoids over that of 5‑fluorouracil, the classic reference cytotoxic agent. By contrast, the glycosylation or the presence of hydroxyl groups in ring B significantly decreased flavonoid anticancer activity. Collectively, these findings suggest a novel, rational design of flavonoid‑related compounds that may improve the treatment of colorectal cancer.

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1	Greenlee RT, Hill-Harmon MB, Murray T and Thun M: Cancer statistics, 2001. CA Cancer J Clin. 51:15–36. 2001. View Article : Google Scholar
2	Dhorajiya BD, Ibrahim AS, Badria FA and Dholakiya BZ: Design and synthesis of novel nucleobase-based barbiturate derivatives as potential anticancer agents. Med Chem Res. August;2013.1 View Article : Google Scholar
3	Quasar Collaborative Group. Gray R, Barnwell J, McConkey C, Hills RK, Williams NS and Kerr DJ: Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 370:2020–2029. 2007. View Article : Google Scholar : PubMed/NCBI
4	Choi EH, Ok HE, Yoon Y, Magnuson BA, Kim MK and Chun HS: Protective effect of anthocyanin-rich extract from bilberry (Vaccinium myrtillus L.) against myelotoxicity induced by 5-fluorouracil. Biofactors. 29:55–65. 2007. View Article : Google Scholar : PubMed/NCBI
5	Meta-Analysis Group In Cancer. Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. Meta-Analysis Group In Cancer. J Clin Oncol. 16:3537–3541. 1998.PubMed/NCBI
6	Jensen SA, Hasbak P, Mortensen J and Sørensen JB: Fluorouracil induces myocardial ischemia with increases of plasma brain natriuretic peptide and lactic acid but without dysfunction of left ventricle. J Clin Oncol. 28:5280–5286. 2010. View Article : Google Scholar : PubMed/NCBI
7	Choti MA: Chemotherapy-associated hepatotoxicity: do we need to be concerned? Ann Surg Oncol. 16:2391–2394. 2009. View Article : Google Scholar : PubMed/NCBI
8	Haggar FA and Boushey RP: Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg. 22:191–197. 2009. View Article : Google Scholar : PubMed/NCBI
9	World Cancer Research Fund/American Institute for Cancer Research. Food, Nutrition and the Prevention of Cancer: a Global Perspective. American Institute for Cancer Research, Washington, DC: AICR; pp. 134–136. 1997
10	Heim KE, Tagliaferro AR and Bobilya DJ: Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutr Biochem. 13:572–584. 2002. View Article : Google Scholar : PubMed/NCBI
11	Yao LH, Jiang YM, Shi J, Tomas-Barberan FA, Datta N, Singanusong R and Chen SS: Flavonoids in food and their health benefits. Plant Foods Hum Nutr. 59:113–122. 2004. View Article : Google Scholar : PubMed/NCBI
12	Koehn FE: Natural products and cancer drug discovery. Humana Press; New York, NY: 2013, View Article : Google Scholar
13	Badria FA and Ibrahim AS: Evaluation of natural anthracene-derived compounds as antimitotic agents. Drug Discov Ther. 7:84–89. 2013.PubMed/NCBI
14	Gao AM, Ke ZP, Shi F and Chen H: Chrysin enhances sensitivity of BEL-7402/ADM cells to doxorubicin by suppressing PI3K/Akt/Nrf2 and ERK/Nrf2 pathway. Chem Biol Interact. 206:100–108. 2013. View Article : Google Scholar : PubMed/NCBI
15	Zhang T, Chen X, Qu L, Wu J, Cui R and Zhao Y: Chrysin and its phosphate ester inhibit cell proliferation and induce apoptosis in HeLa cells. Bioorg Med Chem. 12:6097–6105. 2004. View Article : Google Scholar : PubMed/NCBI
16	Khoo BY, Chua SL and Balaram P: Apoptotic effects of chrysin in human cancer cell lines. Int J Mol Sci. 11:2188–2199. 2010. View Article : Google Scholar : PubMed/NCBI
17	Zhang Q, Zhao XH and Wang ZJ: Cytotoxicity of flavones and flavonols to a human esophageal squamous cell carcinoma cell line (KYSE-510) by induction of G2/M arrest and apoptosis. Toxicol In Vitro. 23:797–807. 2009. View Article : Google Scholar : PubMed/NCBI
18	Lirdprapamongkol K, Sakurai H, Abdelhamed S, Yokoyama S, Maruyama T, Athikomkulchai S, Viriyaroj A, Awale S, Yagita H, Ruchirawat S, Svasti J and Saiki I: A flavonoid chrysin suppresses hypoxic survival and metastatic growth of mouse breast cancer cells. Oncol Rep. 30:2357–2364. 2013.PubMed/NCBI
19	Samarghandian S, Afshari JT and Davoodi S: Chrysin reduces proliferation and induces apoptosis in the human prostate cancer cell line PC-3. Clinics (Sao Paulo). 66:1073–1079. 2011. View Article : Google Scholar : PubMed/NCBI
20	Kuntz S, Wenzel U and Daniel H: Comparative analysis of the effects of flavonoids on proliferation, cytotoxicity, and apoptosis in human colon cancer cell lines. Eur J Nutr. 38:133–142. 1999. View Article : Google Scholar : PubMed/NCBI
21	Wenzel U and Daniel H: Early and late apoptosis events in human transformed and non-transformed colonocytes are independent on intracellular acidification. Cell Physiol Biochem. 14:65–76. 2004. View Article : Google Scholar : PubMed/NCBI
22	Thomas CM, Wood RC III, Wyatt JE, Pendleton MH, Torrenegra RD, Rodriguez OE, Harirforoosh S, Ballester M, Lightner J, Krishnan K and Ramsauer VP: Anti-neoplastic activity of two flavone isomers derived from Gnaph alium elegans and Achyrocline bogotensis. PLoS One. 7:e398062012. View Article : Google Scholar : PubMed/NCBI
23	Austin CA, Patel S, Ono K, Nakane H and Fisher LM: Site-specific DNA cleavage by mammalian DNA topoisomerase II induced by novel flavone and catechin derivatives. Biochem J. 282:883–889. 1992.PubMed/NCBI
24	Marozienė A, Nemeikaitė-Čėnienė A, Vidžiūnaitė R and Čėnas N: Correlation between mammalian cell cytotoxicity of flavonoids and the redox potential of phenoxyl radical/phenol couple. Acta Biochim Pol. 59:299–305. 2012.PubMed/NCBI