Bullatacin triggered ABCB1-overexpressing cell apoptosis via the mitochondrial-dependent pathway.
This paper was to explore bullatacin-mediated multidrug-resistant cell apoptosis at extremely low concentration. To investigate its precise mechanisms, the pathway of cell apoptosis induced by bullatacin was examined. Bullatacin causes an upregulation of ROS and a downregulation of DeltaPsi(m) in a concentration-dependent manner in ABCB1-overexpressing KBv200 cells. In addition, cleavers of caspase-9, caspase-3, and PARP were observed following the release of cytochrome c from mitochondria after bullatacin treatment. However, neither cleavage of caspase-8 nor change of expression level of bcl-2, bax and Fas was observed by the same treatment. Pretreating KBv200 cells with N-acetylcysteine, an antioxidant modulator, resulted in a significant reduction of ROS generation and cell apoptosis induced by bullatacin. Bullatacin-induced apoptosis was antagonized by z-LEHD-fmk, a caspase-9 inhibitor, but not by z-IETD-fmk, a caspase-8 inhibitor. These implied that apoptosis of KBv200 cells induced by bullatacin was associated with the mitochondria-dependent pathway that was limited to activation of apical caspase-9.
Liang
Yong-Ju
YJ
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, China.
Zhang
Xu
X
Dai
Chun-Ling
CL
Zhang
Jian-Ye
JY
Yan
Yan-Yan
YY
Zeng
Mu-Sheng
MS
Chen
Li-Ming
LM
Fu
Li-Wu
LW
D017209:Apoptosis / Q000187:drug effects*; D005663:Furans / Q000008:administration & dosage*; D006801:Humans; D007306:Insecticides / Q000008:administration & dosage; D007624:KB Cells; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
D005663:Furans; D007306:Insecticides; C061022:bullatacin