Among hydroxycinnamic acids, caffeic, ferulic and p-coumaric acids have received considerable attention due to their biological activities. However, studies related to the biological activities of o-coumaric acid (OCA) are limited. In this regard, this study was designed to determine the chemopreventive potential of OCA in human breast cancer cells (MCF-7). The EC50 value of OCA was found to be 4.95 mM and was used throughout the study. Caspase-3 protein and mRNA levels increased by 59% and 72%. Similarly, protein and mRNA levels of Bax were increased by 115% and 152%. However, OCA treatment caused 48% and 35% decreases in Bcl-2 protein and mRNA levels. Cyclin D1 and cyclin dependent kinase-2 protein and mRNA levels decreased significantly. Moreover, p53 protein and mRNA levels increased by 178% and 245%, respectively. In addition to p53, PTEN protein and mRNA levels were induced. Although, CYP1A1, CYP1A2 and CY2E1 mRNA levels increased, CYP3A4 and CYP2C9 mRNA levels decreased in response to OCA treatment. These results suggest that OCA demonstrates anticarcinogenic activity on MCF-7 cells by activating multiple pathways. However, it also has high carcinogen activating and drug interaction potential. Therefore, serious precautions must be taken before using OCA.
JemalA., BrayF., CenterM.M., FerlayJ., WardE., FormanD. (2011) Global cancer statistics. CA: A Cancer Journal for Clinicians, 61, 69–90.
2.
HuangW.Y., CaiY.Z., ZhangY. (2010) Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention. Nutrition and Cancer, 62, 1–20.
3.
DaiJ., MumperR.J. (2010) Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules, 15, 7313–7352.
4.
LandeteJ.M. (2012) Updated knowledge about polyphenols: functions, bioavailability, metabolism, and health. Critical Reviews of Food Science and Nutrition, 52, 936–948.
5.
RobbinsR.J. (2003) Phenolic acids in foods: an overview of analytical methodology. Journal of Agricultural Food Chemistry, 51, 2866–2887.
6.
RadtkeJ., LinseisenJ., WolframG. (1998) Phenolic acid intake of adults in a Bavarian subgroup of the national food consumption survey. Zeitschrift fuer Ernahrungswiss, 37, 190–197.
7.
ScalbertA., WilliamsonG. (2000) Dietary intake and bioavailability of polyphenols. Journal of Nutrition, 130, 2073S–2085.
8.
(a) KampaM., AlexakiV.I., NotasG., NifliA.P., NistikakiA., HatzoglouA., BakogeorgouE., KouimtzoglouE., BlekasG., BoskouD., GravanisA., CastanasE. (2004) Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action. Breast Cancer Research, 6, 63–74;(b) Chuang JY, Tsai YY, Chen SC, Hsieh TJ, Chung JG. (2005) Induction of G0/G1 arrest and apoptosis by 3-hydroxycinnamic acid in human cervix epithelial carcinoma (HeLa) cells. In Vivo, 19, 683–688; (c) Khanduja KL, Avti PK, Kumar S, Mittal N, Sohi KK, Pathak CM. (2006) Anti-apoptotic activity of caffeic acid, ellagic acid and ferulic acid in normal human peripheral blood mononuclear cells: a Bcl-2 independent mechanism. Biochimica et Biophysica Acta, 1760, 283–289.
9.
(a) ChenC.J., HsuM.H., KuoS.C., LaiY.Y., ChungJ.G., HuangL.J. (2007) (2E)-N,N-dibutyl-3-(4-hydroxy-3-methoxyphenyl) acrylamide induces apoptosis and cell cycle arrest in HL-60 cells. Anticancer Research, 27, 343–349;(b) Balakrishnan S, Manoharan S, Alias LM, Nirmal MR. (2010) Effect of curcumin and ferulic acid on modulation of expression pattern of p53 and bcl-2 proteins in 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis. Indian Journal of Biochemistry and Biophysics, 47, 7–12; (c) Chang WC, Hsieh CH, Hsiao MW, Lin WC, Hung YC, Ye JC. (2010) Caffeic acid induces apoptosis in human cervical cancer cells through the mitochondrial pathway. Taiwanese Journal of Obstetrics & Gynecology, 49, 419–424; (d) Ho HC, Chang HC, Ting CT, Kuo CY, Yang VC. (2012) Caffeic acid phenethyl ester inhibits proliferation and migration, and induces apoptosis in platelet-derived growth factor-BB-stimulated human coronary smooth muscle cells. Journal of Vascular Research, 49, 24–32; (e) Xiang D, Wang D, He Y, Xie J, Zhong Z, Li Z, Xie J. (2006) Caffeic acid phenethyl ester induces growth arrest and apoptosis of colon cancer cells via the beta-catenin/T-cell factor signaling. Anticancer Drugs, 17, 753–762.
JanickeB., HegardtC., KroghM., OnningG., AkessonB., CirenajwisH.M., OredssonS.M. (2011) The antiproliferative effect of dietary fiber phenolic compounds ferulic acid and p-coumaric acid on the cell cycle of Caco-2 cells. Nutrition and Cancer, 63, 611–622.
12.
(a) BartkovaJ., LukasJ., MüllerH., LützhøftD., StraussM., BartekJ. (1994) Cyclin D1 protein expression and function in human breast cancer. International Journal of Cancer, 57, 353–361;(b) Bharti AC, Takada Y, Shishodia S, Aggarwal BB. (2004) Evidence that receptor activator of nuclear factor (NF)-kappaB ligand can suppress cell proliferation and induce apoptosis through activation of a NF-kappaB-independent and TRAF6-dependent mechanism. Journal of Biological Chemistry, 279, 6065–6076; (c) Sebastian S, Azzariti A, Silvestris N, Porcelli L, Russo A, Paradiso A. (2010) p53 as the main traffic controller of the cell signaling network. Frontiers in Bioscience, 15, 1172–1190.
13.
(a) LiontasA., YegerH. (2004) Curcumin and resveratrol induce apoptosis and nuclear translocation and activation of p53 in human neuroblastoma. Anticancer Research, 24, 987–998;(b) Koide A, Fuwa K, Furukawa F, Hirose M, Nishikawa A, Mori Y. (1999) Effect of cigarette smoke on the mutagenic activation of environmental carcinogens by rodent liver. Mutation Research, 428, 165–176; (c) Nishikawa A, Furukawa F, Miyauchi M, Son HY, Okazaki K, Koide A, Mori Y, Hirose M. (2002) Enhancement by cigarette smoke exposure of 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline-induced rat hepatocarcinogenesis in close association with elevation of hepatic CYP1A2. Japanese Journal of Cancer Research, 93, 24–31; (d) Guengerich FP, Kim DH, Iwasaki M. (1991) Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chemical Research in Toxicology, 4, 168–179; (e) Krishnan K, Brodeur J. (1991) Toxicological consequences of combined exposure to environmental pollutants. Archives of Complex Environmental Studies, 3, 1–106.
14.
ArincE., ArslanS., BozcaarmutluA., AdaliO. (2007) Effects of diabetes on rabbit kidney and lung CYP2E1 and CYP2B4 expression and drug metabolism and potentiation of carcinogenic activity of N-nitrosodimethylamine in kidney and lung. Food and Chemical Toxicology, 45, 107–118.
15.
SenA., OzgunO., ArincE., ArslanS. (2012) Diverse action of acrylamide on cytochrome P450 and glutathione S-transferase isozyme activities, mRNA levels and protein levels in human hepatocarcinoma cells. Cell Biology and Toxicology, 28, 175–186.
16.
SugimotoK., ArakiN., OhmoriM., HaradaK., CuiY., TsuruokaS., KawaguchiA., FujimuraA. (2006) Interaction between grapefruit juice and hypnotic drugs: comparison of triazolam and quazepam. European Journal of Clinical Pharmacology, 62, 209–215.
17.
SenA., ArincE. (1998) Preparation of highly purified cytochrome P4501A1 from leaping mullet (Liza saliens) liver microsomes and its biocatalytic, molecular and immunochemical properties. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 121, 249–265.
18.
LeeS.J., HedstromO.R., FischerK., Wang-BuhlerJ.L., SenA., CokI., BuhlerD.R. (2001) Immunohistochemical localization and differential expression of cytochrome P450 3A27 in the gastrointestinal tract of rainbow trout. Toxicology and Applied Pharmacology, 177, 94–102.
19.
LaemmliU.K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227, 680–685.
