TY - JOUR
T1 - Ceramide accumulation is independent of camptothecin-induced apoptosis in prostate cancer LNCaP cells
AU - Akao, Yukihiro
AU - Kusakabe, Suzuno
AU - Banno, Yoshiko
AU - Kito, Mariko
AU - Nakagawa, Yoshihito
AU - Tamiya-Koizumi, Keiko
AU - Hattori, Masnori
AU - Sawada, Motoshi
AU - Hirabayasi, Yoshio
AU - Ohishi, Nobuko
AU - Nozawa, Yoshinori
N1 - Funding Information:
This work was supported in part by Grant-in-Aid for Scientific Research on Priority Areas, Grant-in-Aid for Creative Basic Research, Grant-in-Aid for Scientific Research (B) and Special Coordinate Funds for Promoting Science and Technology from The Ministry of Education, Culture, Sports, Science, and Technology, the Japanese Government, and Special Coordination Funds for Promoting Science and Technology from the Science and Technology Agency of Japan. The authors thank Dr. T. Deguchi (Gifu University School of Medicine) for the gift of the strains of LNCaP and PC3 cells.
PY - 2002
Y1 - 2002
N2 - We have investigated to determine the source of ceramide produced during the genotoxic apoptosis induced by the anti-cancer drug, camptothecin (CPT), in human prostate cancer LNCaP cells by measuring the activities of acid and neutral sphingomyelinases (SMase) and by using fumonisinB1 (FB1), the inhibitor of ceramide synthase involving de novo synthesis of ceramide. In contrast to time-dependent elevation of intracellular ceramide level after CPT-treatment, the activities of both SMases were not increased but rather decreased. Instead, pretreatment for 3 h with FB1 (100 μM), an inhibitor of ceramide synthase, almost completely abrogated ceramide accumulation observed in cells exposed to CPT for 18 h. These results indicate that ceramide is produced via de novo pathway but not via sphingomyelin hydrolysis pathway. Furthermore, it is to be noted that the pretreatment with FB1 did not affect the CPT-induced apoptosis as assessed by DNA ladder formation, Hoechst 33342 staining, flow cytometry, and mitochondrial potential thereby leading us to propose that ceramide accumulation is independent of apoptosis in this system.
AB - We have investigated to determine the source of ceramide produced during the genotoxic apoptosis induced by the anti-cancer drug, camptothecin (CPT), in human prostate cancer LNCaP cells by measuring the activities of acid and neutral sphingomyelinases (SMase) and by using fumonisinB1 (FB1), the inhibitor of ceramide synthase involving de novo synthesis of ceramide. In contrast to time-dependent elevation of intracellular ceramide level after CPT-treatment, the activities of both SMases were not increased but rather decreased. Instead, pretreatment for 3 h with FB1 (100 μM), an inhibitor of ceramide synthase, almost completely abrogated ceramide accumulation observed in cells exposed to CPT for 18 h. These results indicate that ceramide is produced via de novo pathway but not via sphingomyelin hydrolysis pathway. Furthermore, it is to be noted that the pretreatment with FB1 did not affect the CPT-induced apoptosis as assessed by DNA ladder formation, Hoechst 33342 staining, flow cytometry, and mitochondrial potential thereby leading us to propose that ceramide accumulation is independent of apoptosis in this system.
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U2 - 10.1016/S0006-291X(02)00462-X
DO - 10.1016/S0006-291X(02)00462-X
M3 - Article
C2 - 12051721
AN - SCOPUS:18444371444
SN - 0006-291X
VL - 294
SP - 363
EP - 370
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -
