The Octyl Ester of Ginsenoside Rh2 Induces Lysosomal Membrane Permeabilization via Bax Translocation.
Ginsenoside Rh2 is a potential pharmacologically active metabolite of ginseng. Previously, we have reported that an octyl ester derivative of ginsenoside Rh2 (Rh2-O), has been confirmed to possess higher bioavailability and anticancer effect than Rh2 in vitro. In order to better assess the possibility that Rh2-O could be used as an anticancer compound, the underlying mechanism was investigated in this study. The present results revealed that lysosomal destabilization was involved in the early stage of cell apoptosis in HepG2 cells induced by Rh2-O. Rh2-O could induce an early lysosomal membrane permeabilization with the release of lysosomal protease cathepsins to the cytosol in HepG2 cells. The Cat B inhibitor (leu) and Cat D inhibitor (pepA) inhibited Rh2-O-induced HepG2 apoptosis as well as tBid production and Δφm depolarization, indicating that lysosomal permeabilization occurred upstream of mitochondrial dysfunction. In addition, Rh2-O induced a significant increase in the protein levels of DRAM1 and Bax (p < 0.05) in lysosomes of HepG2 cells. Knockdown of Bax partially inhibited Rh2-O-induced Cat D release from lysosomes. Thus it was concluded that Rh2-O induced apoptosis of HepG2 cells through activation of the lysosomal-mitochondrial apoptotic pathway involving the translocation of Bax to the lysosome.
State Key Laboratory of Food Science and Technology, Institute for Advanced Study, Nanchang University, Nanchang, Jiangxi 330047, China. xinganchenfang@163.com.|College of Food Science, Nanchang University, Nanchang, Jiangxi 330047, China. xinganchenfang@163.com.
Fang
F
Chen
State Key Laboratory of Food Science and Technology, Institute for Advanced Study, Nanchang University, Nanchang, Jiangxi 330047, China. zhangbingair@hotmail.com.
Bing
B
Zhang
State Key Laboratory of Food Science and Technology, Institute for Advanced Study, Nanchang University, Nanchang, Jiangxi 330047, China. yong.sun@canada.ca.|College of Food Science, Nanchang University, Nanchang, Jiangxi 330047, China. yong.sun@canada.ca.
Yong
Y
Sun
State Key Laboratory of Food Science and Technology, Institute for Advanced Study, Nanchang University, Nanchang, Jiangxi 330047, China. m15179146869@163.com.|College of Food Science, Nanchang University, Nanchang, Jiangxi 330047, China. m15179146869@163.com.
Zeng-Xing
ZX
Xiong
State Key Laboratory of Food Science and Technology, Institute for Advanced Study, Nanchang University, Nanchang, Jiangxi 330047, China. ncuskpenghan@163.com.|College of Food Science, Nanchang University, Nanchang, Jiangxi 330047, China. ncuskpenghan@163.com.
Han
H
Peng
State Key Laboratory of Food Science and Technology, Institute for Advanced Study, Nanchang University, Nanchang, Jiangxi 330047, China. dengzy@ncu.edu.cn.|College of Food Science, Nanchang University, Nanchang, Jiangxi 330047, China. dengzy@ncu.edu.cn.
Ze-Yuan
ZY
Deng
State Key Laboratory of Food Science and Technology, Institute for Advanced Study, Nanchang University, Nanchang, Jiangxi 330047, China. hujiangning2005@hotmail.com.|College of Food Science, Nanchang University, Nanchang, Jiangxi 330047, China. hujiangning2005@hotmail.com.
Jiang-Ning
JN
Hu
D017209:Apoptosis / Q000187:drug effects; D002403:Cathepsins; D049109:Cell Proliferation; D003600:Cytosol; D004952:Esters; D005786:Gene Expression Regulation; D020868:Gene Silencing; D036145:Ginsenosides / Q000737:chemistry* / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008247:Lysosomes / Q000187:drug effects* / Q000502:physiology; D053078:Membrane Potential, Mitochondrial; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010539:Permeability; D021381:Protein Transport / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
C494826:BAX protein, human; C512709:DRAM1 protein, human; D004952:Esters; D036145:Ginsenosides; D008565:Membrane Proteins; D051028:bcl-2-Associated X Protein; C055305:ginsenoside Rh2; D002403:Cathepsins
Bax; Ginsenoside Rh2; apoptosis; lysosomal membrane permeabilization; mitochondria dysfunction; octyl ester derivative