title: Myricetin and methyl eugenol combination enhances the anticancer activity, cell cycle arrest and apoptosis induction of cis-platin against HeLa cervical cancer cell lines.
abstract: Drug combination therapies are common practice in the treatment of cancer. In this study, we evaluated the anticancer effects of myricetin (MYR), methyl eugenol (MEG) and cisplatin (CP) both separately as well as in combination against cervical cancer (HeLa) cells. To demonstrate whether MYR and MEG enhance the anticancer activity of CP against cervical cancer cells, we treated HeLa cells with MYR and MEG alone or in combination with cisplatin and evaluated cell growth and apoptosis using MTT (3 (4, 5 dimethyl thiazol 2yl) 2, 5 diphenyltetrazolium bromide) assay, LDH release assay, flow cytometry and fluorescence microscopy. The results revealed that, as compared to single drug treatment, the combination of MYR or MEG with CP resulted in greater effect in inhibiting cancer cell growth and inducing apoptosis. Cell apoptosis induction, Caspase-3 activity, cell cycle arrest and mitochondrial membrane potential loss were systematically studied to reveal the mechanisms of synergy between MYR, MEG and CP. Combination of MYR or MEG with CP resulted in more potent apoptosis induction as revealed by fluorescence microscopy using Hoechst 33258 and AO-ETBR staining. The combination treatment also increased the number of cells in G0/G1 phase dramatically as compared to single drug treatment. Mitochondrial membrane potential loss (ΛΨm) as well as Caspase-3 activity was much higher in combination treatment as compared to single drug treatment. Findings of this investigation suggest that MYR and MEG combined with cisplatin is a potential clinical chemotherapeutic approach in human cervical cancer.
authors.affiliation: Department of Gynaecology, Fifth Affiliated Hospital of Xinjiang Medical University Urumqi 830011, Xinjiang, China.
authors.forename: Jin-Ling
authors.initials: JL
authors.lastname: Yi
authors.affiliation: Department of Cardiac Function, Fifth Affiliated Hospital of Xinjiang Medical University Urumqi 830011, Xinjiang, China.
authors.forename: Song
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Gynaecology, Fifth Affiliated Hospital of Xinjiang Medical University Urumqi 830011, Xinjiang, China.
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Shen
authors.affiliation: Department of Gynaecology, Fifth Affiliated Hospital of Xinjiang Medical University Urumqi 830011, Xinjiang, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gynaecology, Fifth Affiliated Hospital of Xinjiang Medical University Urumqi 830011, Xinjiang, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Department of Gynaecology, Fifth Affiliated Hospital of Xinjiang Medical University Urumqi 830011, Xinjiang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Gynaecology, First Affiliated Hospital of Xinjiang Medical University Urumqi 830045, Xinjiang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D004338:Drug Combinations; D004347:Drug Interactions; D004357:Drug Synergism; D005054:Eugenol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D006367:HeLa Cells; D006801:Humans; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism
chemical_list: D004338:Drug Combinations; D005419:Flavonoids; C005223:methyleugenol; D005054:Eugenol; C040015:myricetin; D053148:Caspase 3; D002945:Cisplatin
keywords: Cervical cancer; apoptosis; cell cycle; combination therapy; methyl eugenol; myricetin