title: Cellular levels of oxidative stress affect the response of cervical cancer cells to chemotherapeutic agents.
abstract: Treatment of advanced and relapsed cervical cancer is frequently ineffective, due in large part to chemoresistance. To examine the pathways responsible, we employed the cervical carcinoma-derived SiHa and CaSki cells as cellular models of resistance and sensitivity, respectively, to treatment with chemotherapeutic agents, doxorubicin, and cisplatin. We compared the proteomic profiles of SiHa and CaSki cells and identified pathways with the potential to contribute to the differential response. We then extended these findings by comparing the expression level of genes involved in reactive oxygen species (ROS) metabolism through the use of a RT-PCR array. The analyses demonstrated that the resistant SiHa cells expressed higher levels of antioxidant enzymes. Decreasing or increasing oxidative stress led to protection or sensitization, respectively, in both cell lines, supporting the idea that cellular levels of oxidative stress affect responsiveness to treatment. Interestingly, doxorubicin and cisplatin induced different profiles of ROS, and these differences appear to contribute to the sensitivity to treatment displayed by cervical cancer cells. Overall, our findings demonstrate that cervical cancer cells display variable profiles with respect to their redox-generating and -adaptive systems, and that these different profiles have the potential to contribute to their responses to treatments with chemotherapy.
authors.affiliation: Department of Basic Sciences, Loma Linda University School of Medicine, 11021 Campus Street, 101 Alumni Hall, Loma Linda, CA 92354, USA.
authors.forename: Maria
authors.identifier: 0000-0002-7559-6713
authors.initials: M
authors.lastname: Filippova
authors.affiliation: Department of Basic Sciences, Loma Linda University School of Medicine, 11021 Campus Street, 101 Alumni Hall, Loma Linda, CA 92354, USA.
authors.forename: Valery
authors.identifier: 0000-0002-7619-9031
authors.initials: V
authors.lastname: Filippov
authors.affiliation: Department of Basic Sciences, Loma Linda University School of Medicine, 11021 Campus Street, 101 Alumni Hall, Loma Linda, CA 92354, USA.
authors.forename: Vonetta M
authors.initials: VM
authors.lastname: Williams
authors.affiliation: Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Kangling
authors.identifier: 0000-0003-2151-9218
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Basic Sciences, Loma Linda University School of Medicine, 11021 Campus Street, 101 Alumni Hall, Loma Linda, CA 92354, USA.
authors.forename: Anatolii
authors.initials: A
authors.lastname: Kokoza
authors.affiliation: Department of Basic Sciences, Loma Linda University School of Medicine, 11021 Campus Street, 101 Alumni Hall, Loma Linda, CA 92354, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Bashkirova
authors.affiliation: Department of Basic Sciences, Loma Linda University School of Medicine, 11021 Campus Street, 101 Alumni Hall, Loma Linda, CA 92354, USA.
authors.forename: Penelope
authors.initials: P
authors.lastname: Duerksen-Hughes
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D002945:Cisplatin