Sanguinarine induces apoptosis in A549 human lung cancer cells primarily via cellular glutathione depletion.
Sanguinarine is a plant-derived benzophenanthridine alkaloid and has been shown to possess anti-tumor activities against various cancer cells. In this study, we investigated whether sanguinarine induces apoptosis in A549 human lung cancer cells. Treatment of A549 cells with sanguinarine induced apoptosis in a dose- and time-dependent manner. Treatment with sanguinarine led to activation of caspases and MAPKs as well as increased MKP-1 expression. Importantly, pretreatment with z-VAD-fmk, a pan caspase inhibitor suppressed the sanguinarine-induced apoptosis in A549 cells. Moreover, pretreatment with NAC, a sulfhydryl group-containing reducing agent strongly suppressed the apoptotic response and caspase activation to sanguinarine. However, the sanguinarine-mediated cytotoxicity in A549 cells was not protected by pharmacological inhibition of MAPKs or MKP-1 siRNA-mediated knockdown of MKP-1. These results collectively suggest that sanguinarine induces apoptosis in A549 cells through cellular glutathione depletion and the subsequent caspase activation.
Jang
Byeong-Churl
BC
Department of Medical Genetic Engineering, Keimyung University School of Medicine, 194 Dongsan-dong, Jung-gu, Daegu 700-712, Republic of Korea. jangbc12@kmu.ac.kr
Park
Jong-Gu
JG
Song
Dae-Kyu
DK
Baek
Won-Ki
WK
Yoo
Sun Kyun
SK
Jung
Kyung-Hwan
KH
Park
Gy-Young
GY
Lee
Tae-Yun
TY
Suh
Seong-Il
SI
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053119:Benzophenanthridines / Q000494:pharmacology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors; D020868:Gene Silencing; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
D000590:Amino Acid Chloromethyl Ketones; D000972:Antineoplastic Agents, Phytogenic; D053119:Benzophenanthridines; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D018696:Neuroprotective Agents; D034741:RNA, Small Interfering; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C005705:sanguinarine; D020929:Mitogen-Activated Protein Kinase Kinases; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D020169:Caspases; D005978:Glutathione