Combination treatment with cyclosporin A and arsenic trioxide induce synergistic cell death via non-apoptotic pathway in uterine cervical cancer cells.

Abstract

Cyclosporin A is an immunosuppressive drug with anti-cancer effect. Arsenic trioxide (As2O3), a well-known cancer-inhibiting drug, induced cytotoxicity via apoptosis and autophagy. The aim of this study is to evaluate the effect of combinational treatment with cyclosporin A and arsenic trioxide on cell viability inhibition in cervical cancer cells. Using MTT assay and combination index, combinational treatment with cyclosporin A and arsenic trioxide induced a synergistic cytotoxic effect in Caski and SiHa cells. Cyclosporin A and arsenic trioxide triggered cell death via non-apoptotic pathway by using annexin V/propidium iodide (PI) assay. Cyclosporin A and arsenic trioxide combined treatment decreased mitochondrial membrane potential and increase reactive oxygen species (ROS) generation. This co-treatment increased LC3B-II expression and autophagosome formation in cervical cancer cells. This study first demonstrated that combinational treatment with cyclosporin A and As2O3 trigger synergistic cytotoxic effect via autophagy in cervical cancer cells.

• Authors: Pei-Ju Wu, I-Lun Hsin, Wei-Li Hung, Maw-Sheng Lee, Po-Hui Wang, Jiunn-Liang Ko
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 368 Pg. 110177 (Dec 01 2022) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 36100036 (Publication Type: Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier B.V.

Chemical References

• Arsenic Trioxide
• Cyclosporine
• Antineoplastic Agents
• Arsenicals
• Oxides

Topics

• Female
• Humans
• Arsenic Trioxide (pharmacology)
• Uterine Cervical Neoplasms (drug therapy)
• Cyclosporine (pharmacology)
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis
• Arsenicals (pharmacology)
• Oxides (pharmacology)
• Cell Line, Tumor