title: Cinnamaldehyde/chemotherapeutic agents interaction and drug-metabolizing genes in colorectal cancer.
abstract: Cinnamaldehyde is an active monomer isolated from the stem bark of Cinnamomum cassia, a traditional oriental medicinal herb, which is known to possess marked antitumor effects in vitro and in vivo. The aim of the present study was to examine the potential advantages of using cinnamaldehyde in combination with chemotherapeutic agents commonly used in colorectal carcinoma (CRC) therapy, as well as to investigate the effect of cinnamaldehyde on chemotherapeutic-associated gene expression. The synergistic interaction of cinnamaldehyde and chemotherapeutic agents on human CRC HT-29 and LoVo cells was evaluated using the combination index (CI) method. The double staining with Annexin V conjugated to fluorescein-isothiocyanate and phosphatidylserine was employed for apoptosis detection. The expression of drug-metabolizing genes, including excision repair cross‑complementing 1 (ERCC1), orotate phosphoribosyltransferase (OPRT), thymidylate synthase (TS), breast cancer susceptibility gene 1 (BRCA1) and topoisomerase 1 (TOPO1), all in HT-29 and LoVo cells, with or without the addition of cinnamaldehyde, was examined by quantitative polymerase chain reaction (PCR). Cinnamaldehyde had a synergistic effect on the chemotherapeutic agents cytotoxicity in HT-29 and LoVo cells. In addition, cinnamaldehyde suppressed BRCA1, TOPO1, ERCC1 and TS mRNA expression, except for OPRT expression, which was markedly upregulated. Our findings indicate that cinnamaldehyde appears to be a promising candidate as an adjuvant in combination therapy with 5-fluorouracil (5-FU) and oxaliplatin (OXA), two chemotherapeutic agents used in CRC treatment. The possible mechanisms of its action may involve the regulation of drug‑metabolizing genes.
authors.affiliation: First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
authors.affiliation: Senior Expert Consultation Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Shen-Lin
authors.initials: SL
authors.lastname: Liu
authors.affiliation: National Clinical Research Base of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Ming-Hao
authors.initials: MH
authors.lastname: Qi
authors.affiliation: Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zou
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols; D019313:BRCA1 Protein / Q000096:biosynthesis; D032904:Cinnamomum aromaticum / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004357:Drug Synergism; D004720:Endonucleases / Q000096:biosynthesis; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019073:HT29 Cells; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D009962:Orotate Phosphoribosyltransferase / Q000096:biosynthesis; D000077150:Oxaliplatin; D013940:Thymidylate Synthase / Q000096:biosynthesis
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000171:Acrolein; D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; C071447:ERCC1 protein, human; D004720:Endonucleases; D004264:DNA Topoisomerases, Type I; C012843:cinnamaldehyde; D005472:Fluorouracil