Caspase-independent autophagic cytotoxicity in etoposide-treated CaSki cervical carcinoma cells.
We studied the in vitro mechanism of etoposide-induced cell death in cervical cancer cells. Etoposide is cytotoxic to these cells, causing cell death by both apoptosis and autophagy, which has recently been described as a possible mechanism for nonapoptotic cell death. Electron microscopy revealed that autophagosomes/autolysosomes exhibited an autophagic appearance in the presence of etoposide. When autophagy was blocked by inhibitors of autophagy, including 3-methyladenine, both the expression of beclin 1 protein and the antitumor effect of etoposide were suppressed. Benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, a pan-caspase inhibitor, reduced etoposide-induced cytotoxicity in CaSki cells. Hence, autophagy and apoptosis likely occur concurrently in etoposide-treated cervical cancer cells.
Lee
Seung-Baek
SB
Department of Medical Bioscience, Graduate School of Medicine, Catholic University Medical College, Seoul, Republic of Korea.
Tong
Seo-Yun
SY
Kim
Jung-Jin
JJ
Um
Soo-Jong
SJ
Park
Jong-Sup
JS
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001343:Autophagy; D000071186:Beclin-1; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018942:Macrolides / Q000494:pharmacology; D008565:Membrane Proteins / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000473:pathology*