Inhibition of growth and sensitization to cisplatin-mediated killing of ovarian cancer cells by polyphenolic chemopreventive agents.
The polyphenolic compounds curcumin and quercetin increased sensitivity of ovarian cancer cells (CAOV3 and SKOV3) to cisplatin. The effect was obtained when the compounds were added simultaneously with cisplatin, as well as when they were added 24 h before. High serum levels of certain cytokines, for example interleukin-6 (IL-6), have been associated with poor prognosis and cisplatin resistance in various forms of cancer. Furthermore, it has been hypothesized that cytokines may increase proliferation, metastasis, and stimulate production of detoxification enzymes and multi-drug resistant proteins. Curcumin inhibits the production of many cytokines. The two ovarian cell lines differ significantly in IL-6 production, and correspondingly the high producer, CAOV3, was less susceptible to cisplatin. Curcumin inhibited the production of IL-6 in this cell suggesting that one of the mechanisms for synergy between cisplatin and curcumin was by reducing the autologous production of IL-6. However, the synergy was also observed in the low IL-6 producer, SKOV3, indicating that the action was most probably a result of multiple targeting. In sum, this study suggests that the compounds, curcumin and quercetin, potentially may be useful for enhancing drug sensitivity in certain cancer.
Chan
Marion M
MM
Department of Microbiology and Immunology, Temple University School of Medicine, North Broad Street, Philadelphia, Pennsylvania 19140, USA. marionc@astro.temple.edu
Fong
Dunne
D
Soprano
Kenneth J
KJ
Holmes
William F
WF
Heverling
Harry
H
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D004396:Coloring Agents; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004359:Drug Therapy, Combination; D005260:Female; D005419:Flavonoids; D006131:Growth Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008658:Inactivation, Metabolic / Q000502:physiology; D015850:Interleukin-6 / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010078:Oxazines; D010636:Phenols / Q000494:pharmacology* / Q000627:therapeutic use; D011108:Polymers / Q000494:pharmacology* / Q000627:therapeutic use; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D014966:Xanthenes
D000970:Antineoplastic Agents; D004396:Coloring Agents; D005419:Flavonoids; D006131:Growth Inhibitors; D015850:Interleukin-6; D010078:Oxazines; D010636:Phenols; D011108:Polymers; D014966:Xanthenes; C005843:resazurin; C012526:quercitrin; D011794:Quercetin; D003474:Curcumin; D002945:Cisplatin