Apoptotic effects of Antrodia cinnamomea fruiting bodies extract are mediated through calcium and calpain-dependent pathways in Hep 3B cells.
Antrodia cinnamomea is well known in Taiwan as a traditional medicine for treating cancer and inflammation. The purpose of this study was to evaluate the apoptotic effects of ethylacetate extract from A. cinnamomea (EAC) fruiting bodies in Hep 3B, a liver cancer cell line. EAC decreased cell proliferation of Hep 3B cells by inducing apoptotic cell death. EAC treatment increased the level of calcium (Ca2+) in the cytoplasm and triggered the subsequent activation of calpain and caspase-12. EAC also initiated the mitochondrial apoptotic pathway through regulation of Bcl-2 family proteins expression, release of cytochrome c, and activation of caspase-9 in Hep 3B cells. Furthermore, the mitochondrial apoptotic pathway amplified the calpain pathway by Bid and Bax interaction and Ca2+ translocation. We have therefore concluded that the molecular mechanisms during EAC-mediated proliferation inhibition in Hep 3B cells were due to: (1) apoptosis induction, (2) triggering of Ca2+/calpain pathway, (3) disruption of mitochondrial function, and (4) apoptotic signaling being amplified by cross-talk between the calpain/Bid/Bax and Ca2+/mitochondrial apoptotic pathways.
Kuo
Po-Lin
PL
Department of Biotechnology, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.
Hsu
Ya-Ling
YL
Cho
Chien-Yu
CY
Ng
Lean-Teik
LT
Kuo
Yueh-Hsiung
YH
Lin
Chun-Ching
CC
D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D053454:Caspase 12; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000276:immunology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D005638:Fruit / Q000737:chemistry; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D020072:Polyporales / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D045304:Cytochromes c; C506444:CASP12 protein, human; D002154:Calpain; D053454:Caspase 12; D020169:Caspases; D002118:Calcium