Induction of apoptosis by aqueous extract of Cordyceps militaris through activation of caspases and inactivation of Akt in human breast cancer MDA-MB-231 Cells.
Cordyceps militaris is well known as a traditional medicinal mushroom and has been shown to exhibit immunostimulatory and anticancer activities. In this study, we investigated the apoptosis induced by an aqueous extract of C. militaris (AECM) via the activation of caspases and altered mitochondrial membrane permeability in human breast cancer MDA-MB-231 cells. Exposure to AECM induced apoptosis, as demonstrated by a quantitative analysis of nuclear morphological change and a flow cytometric analysis. AECM increased hyperpolarization of mitochondrial membrane potential and promoted the activation of caspases. Both the cytotoxic effect and apoptotic characteristics induced by AECM treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role of caspase-3 in the observed cytotoxic effect. AECM-induced apoptosis was associated with the inhibition of Akt activation in a time-dependent manner, and pretreatment with LY294002, a PI3K/Akt inhibitor, significantly increased AECM-induced apoptosis. The results indicated that AECM-induced apoptosis may relate to the activation of caspase-3 and mitochondria dysfunctions that correlate with the inactivation of Akt.
Jin
Cheng-Yun
CY
Department of Biomaterial Control (BK21 Program), Dongeui University Graduate School and Department of Biochemistry,Dongeui University College of Oriental Medicine, Busan 614-052, Korea.
Kim
Gi-Young
GY
Choi
Yung Hyun
YH
D017209:Apoptosis; D001943:Breast Neoplasms; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D032661:Cordyceps / Q000737:chemistry*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D020169:Caspases; D002867:Chromones; D015853:Cysteine Proteinase Inhibitors; D004365:Drugs, Chinese Herbal; D009025:Morpholines; D009842:Oligopeptides; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one