Induction of apoptosis and inhibition of telomerase activity in human lung carcinoma cells by the water extract of Cordyceps militaris.
Cordyceps militaris is well known as a traditional medicinal mushroom and is a potentially interesting candidate for use in cancer treatment. In this study, the potential of the water extract of C. militaris (WECM) to induce apoptosis in human lung carcinoma A549 cells and its effects on telomerase activity were investigated. The growth inhibition and apoptosis induction by WECM treatment in A549 cells was associated with the induction of Fas, catalytic activation of caspase-8, and Bid cleavage. Activation of caspases, downregulation of anti-apoptotic Bcl-2 expression, and upregulation of pro-apoptotic Bax protein were also observed in WECM-treated cells. However, the cytotoxic effects and apoptotic characteristics induced by WECM were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role that caspase-3 plays in the process. In addition, WECM exerted a dose-dependent inhibition of telomerase activity via downregulation of human telomerase reverse transcriptase (hTERT), c-myc and Sp1 expression. Taken together, the data from this study indicate that WECM induces the apoptosis of A549 cells through a signaling cascade of death receptor-mediated extrinsic and mitochondria-mediated intrinsic caspase pathways. It was also conclude that apoptotic events due to WECM were mediated with diminished telomerase activity through the inhibition of hTERT transcriptional activity.
Park
Sang Eun
SE
Department of East-West Cancer Center, College of Oriental Medicine, Daejeon University, Daejeon 301-724, Republic of Korea.
Yoo
Hwa Seung
HS
Jin
Cheng-Yun
CY
Hong
Sang Hoon
SH
Lee
Yeon-Weol
YW
Kim
Byung Woo
BW
Lee
Shin Hwa
SH
Kim
Wun-Jae
WJ
Cho
Chong Kwan
CK
Choi
Yung Hyun
YH
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D032661:Cordyceps / Q000737:chemistry*; D053938:DNA Fragmentation / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012997:Solvents; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014867:Water
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D012997:Solvents; D014867:Water; D012313:RNA; D019098:Telomerase; D020169:Caspases