title: Alterations of microRNA expression patterns in human cervical carcinoma cells (Ca Ski) toward 1'S-1'-acetoxychavicol acetate and cisplatin.
abstract: The aims of this study were to investigate the combined effects of a natural compound 1'S-1'-acetoxychavicol acetate (ACA) with cisplatin (CDDP) on HPV-positive human cervical carcinoma cell lines (Ca Ski-low cisplatin sensitivity and HeLa-high cisplatin sensitivity), and to identify microRNAs (miRNAs) modulated in response toward ACA and/or CDDP. It was revealed that both ACA and CDDP induced dose- and time-dependent cytotoxicity when used as a stand-alone agent, while synergistic effects were observed when used in combination with a combination index (CI) value of 0.74 ± 0.01 and 0.85 ± 0.01 in Ca Ski and HeLa cells, respectively. A total of 25 miRNAs were found to be significantly differentially expressed in response to ACA and/or CDDP. These include hsa-miR-138, hsa-miR-210, and hsa-miR-744 with predicted gene targets involved in signaling pathways regulating apoptosis and cell cycle progression. In conclusion, ACA acts as a chemosensitizer which synergistically potentiates the cytotoxic effect of CDDP in cervical cancer cells. The altered miRNA expression upon administration of ACA and/or CDDP suggests that miRNAs play an important role in anticancer drug responses, which can be manipulated for therapeutic purposes.
authors.affiliation: Institute of Biological Science (Genetics & Molecular Biology), University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Neoh Hun
authors.initials: NH
authors.lastname: Phuah
authors.forename: Lionel L A
authors.initials: LL
authors.lastname: In
authors.forename: Mohamad Nurul
authors.initials: MN
authors.lastname: Azmi
authors.forename: Halijah
authors.initials: H
authors.lastname: Ibrahim
authors.forename: Khalijah
authors.initials: K
authors.lastname: Awang
authors.forename: Noor Hasima
authors.initials: NH
authors.lastname: Nagoor
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001592:Benzyl Alcohols / Q000494:pharmacology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D001592:Benzyl Alcohols; D035683:MicroRNAs; D002945:Cisplatin; C047948:1'-acetoxychavicol acetate