title: Anti-proliferative and pro-apoptotic effects from sequenced combinations of andrographolide and cisplatin on ovarian cancer cell lines.
abstract: Andrographolide (Andro) is a diterpenoid that is isolated from Andrographis paniculata and reported to be active against several cancer cell lines. However, few in-depth studies have been carried out on its effects on ovarian cancer cell lines alone or in combination with cisplatin (Cis), which is commonly used to treat ovarian cancer. The aim of this study was to determine the anti-proliferative and apoptotic effects of Andro administered alone and in combination with Cis in the ovarian A2780 and A2780(cisR) cancer cell lines using five different sequences of administration (Cis/Andro h): 0/0h, 4/0 h, 0/4 h, 24/0 h and 0/24 h. The results were evaluated in terms of medium-effect dose (Dm) and combination indices (CI) using the CalcuSyn software. Unlike Cis, whose activity was lower in the resistant A2780(cisR) cell line than in the parent A2780 cell line, Andro was found to be three times more active in the A2780(cisR) cell line as compared to that in A2780 cell line. Synergism was observed when Cis and Andro were administered using the sequences 0/4 h and 4/0 h. The percentage of apoptotic cell death was found to be greater for the 0/4 h combination of Andro and Cis as compared to those values from single-drug treatments. The results may be clinically significant if confirmed in vivo.
authors.affiliation: Discipline of Biomedical Science, The University of Sydney, 75 East Street, Lidcombe NSW 1825, Australia. Fazlul.huq@sydney.edu.au and Nurhanan Murni Yunos, Drug Discovery Centre, Natural Products Division, Forest Research Institute Malaysia, Kepong, Selangor, Malaysia. E-mail: hanan@frim.gov.my.
authors.forename: Nurhanan M
authors.initials: NM
authors.lastname: Yunos
authors.forename: Siti S M
authors.initials: SS
authors.lastname: Mutalip
authors.forename: Muhammad H
authors.initials: MH
authors.lastname: Jauri
authors.forename: Jun Q
authors.initials: JQ
authors.lastname: Yu
authors.forename: Fazlul
authors.initials: F
authors.lastname: Huq
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D053938:DNA Fragmentation; D004224:Diterpenes / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; C030419:andrographolide; D002945:Cisplatin
keywords: Andrographolide; anti-proliferative; apoptosis; cisplatin; ovarian cancer; synergism