title: Isorhamnetin flavonoid synergistically enhances the anticancer activity and apoptosis induction by cis-platin and carboplatin in non-small cell lung carcinoma (NSCLC).
abstract: The development of novel antitumor drugs for the treatment of non-small cell lung carcinoma NSCLC is imperative in order to improve the efficacy of lung cancer therapy and prognosis. In the current study, we demonstrated the antitumor activity of isorhamnetin and its combinations with cisplatin and carboplatin against A-549 lung cancer cells. In order to assess the anticancer enhancing effect of isorhamnetin on cisplatin and carboplatin, A-549 cells were treated with isorhamnetin, cisplatin, carboplatin and their combinations and cell viability, cell apoptosis, cell cycle arrest as well as loss of mitochondrial membrane potential were evaluated by MTT assay, flow cytometry, confocal microscopy and fluorescence microscopy. The effect of the drugs on cancer cell migration, microtubule depolymerization as well activation of caspases was also studied. The results revealed that, as compared to single drug treatment, the combination of isorhamnetin with cisplatin and carboplatin resulted in greater effect in inhibiting cancer cell growth and inducing apoptosis. Combination of isorhamnetin with cisplatin and carboplatin resulted in more potent apoptosis induction as revealed by fluorescence microscopy using AO/PI double staining. Isorhamnetin and its combinations also triggered microtubule distortion and depolymerization. The combination of isorhamnetin with cisplatin and carboplatin increased the number of cells in G2/M phase dramatically as compared to single drug treatment. Moreover, isorhamnetin and its combinations with known anticancer drugs induced disruption of the mitochondrial membrane potential as well as activation of caspases 3, 9 and poly-(ADP-ribose) polymerase in A-549 cells. Isorhamnetin as well as its combinations with cisplatin and carboplatin resulted in inhibition of cancer cell migration significantly. Results of the current study suggest that isorhamnetin combinations with cisplatin and carboplatin might be a potential clinical chemotherapeutic approach for NSCLC.
authors.affiliation: Department of Radiation Oncology, Jinan Military General Hospital Jinan 250031, China.
authors.forename: Bao-Yi
authors.initials: BY
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Jinan Military General Hospital Jinan 250031, China.
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Jinan Military General Hospital Jinan 250031, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Gong
authors.affiliation: Department of Radiation Oncology, Jinan Military General Hospital Jinan 250031, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Radiation Oncology, Jinan Military General Hospital Jinan 250031, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Lv
authors.affiliation: Department of Radiation Oncology, Jinan Military General Hospital Jinan 250031, China.
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Yuan
authors.affiliation: Department of Radiation Oncology, Jinan Military General Hospital Jinan 250031, China.
authors.forename: Shao-Rong
authors.initials: SR
authors.lastname: Han
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016190:Carboplatin / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018613:Microscopy, Confocal; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C047368:3-methylquercetin; D011794:Quercetin; D016190:Carboplatin; D002945:Cisplatin
keywords: Non-small cell lung carcinoma; apoptosis; cell migration; chemotherapy; isorhamnetin; tubulin