MAC-related mitochondrial pathway in oroxylin-A-induced apoptosis in human hepatocellular carcinoma HepG2 cells.
Oroxylin A is a flavonoid isolated from the root of Scutellaria baicalensis Georgi. Our previous work demonstrated that the anti-tumor activity of oroxylin A was mainly attributed to its apoptosis inducing effect in cells. The present study explores the exact molecular mechanism of oroxylin A-induced apoptosis in tumor cells. We showed that oroxylin A-induced apoptosis in HepG2 cells was achieved through mitochondrial pathway. We also investigated which mitochondrial channels, PTP or MAC or both, were involved in the permeabilization of the mitochondrial outer membrane after treatment with oroxylin A. The results showed that oroxylin A-induced apoptosis in a PTP-independent manner; therefore, we focused our attention on MAC. As Bax is an essential constituent of MAC in certain systems, we examined the activation, subcellular location, oligomeric structure of Bax in HepG2 cells treated with oroxylin A. Moreover, our results showed that overexpression of Bcl-2 inhibited oroxylin A-induced apoptosis. In summary, we have demonstrated that opening of MAC, but not PTP, played a key role in oroxylin A-induced activation of mitochondrial apoptotic pathway in HepG2 cells.
Liu
Wei
W
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Mu
Rong
R
Nie
Fei-Fei
FF
Yang
Yong
Y
Wang
Jun
J
Dai
Qin-Sheng
QS
Lu
Na
N
Qi
Qi
Q
Rong
Jing-Jing
JJ
Hu
Rong
R
Wang
Xiao-Tang
XT
You
Qi-Dong
QD
Guo
Qing-Long
QL
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor / Q000166:cytology / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D019281:Dimerization; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000502:physiology*; D008113:Liver Neoplasms / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000502:physiology; D051336:Mitochondrial Membranes / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D009363:Neoplasm Proteins / Q000737:chemistry / Q000502:physiology*; D021381:Protein Transport / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D005419:Flavonoids; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; D016572:Cyclosporine