Anticancer effects of cantharidin in A431 human skin cancer (Epidermoid carcinoma) cells in vitro and in vivo.
Cantharidin (CTD), a potential anticancer agent of Traditional Chinese Medicine has cytotxic effects in different human cancer cell lines. The cytotoxic effects of CTD on A431 human skin cancer (epidermoid carcinoma) cells in vitro and in A431 cell xenograft mouse model were examined. In vitro, A431 human skin cell were treated with CTD for 24 and 48 h. Cell phase distribution, ROS production, Ca2+release, Caspase activity and the level of apoptosis associated proteins were measured. In vivo, A431 cell xenograft mouse model were examined. CTD-induced cell morphological changes and decreased percentage of viable A431 cells via G0/G1 phase arrest and induced apoptosis. CTD-induced G0/G1 phase arrest through the reduction of protein levels of cyclin E, CDK6, and cyclin D in A431 cells. CTD-induced cell apoptosis of A431 cells also was confirm by DNA gel electrophoresis showed CTD-induced DNA fragmentation. CTD reduced the mitochondrial membrane potential and stimulated release of cytochrome c, AIF and Endo G in A431 cells. Flow cytometry demonstrated that CTD increased activity of caspase-8, -9 and -3. However, when cells were pretreated with specific caspase inhibitors activity was reduced and cell viability increased. CTD increased protein levels of death receptors such as DR4, DR5, TRAIL and levels of the active form of caspase-8, -9 and -3 in A431 cells. AIF and Endo G proteins levels were also enhanced by CTD. In vivo studies showed that CTD significantly inhibited A431 cell xenograft tumors in mice. Taken together, these in vitro and in vivo results provide insight into the mechanisms of CTD on cell growth and tumor production. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 723-738, 2017.
Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, 404.
Chi-Chuan
CC
Li
School of Dentistry, China Medical University, Taichung, Taiwan, 404.
Fu-Shun
FS
Yu
Department of Biotechnology, Asia University, Taichung, Taiwan, 413.
Ming-Jen
MJ
Fan
Department of Chinese-Western Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, 402.|School of Medicine, Chung Shan Medical University, Taichung, Taiwan, 402.
Ya-Yin
YY
Chen
School of Pharmacy, China Medical University, Taichung, Taiwan, 404.
Jin-Cherng
JC
Lien
Division of Neurosurgical Oncology, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan, 407.|Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, 114.
Yu-Cheng
YC
Chou
Department of Clinical Pathology, Cheng Hsin General Hospital, Taipei, Taiwan, 112.
Hsu-Feng
HF
Lu
School of Chinese Medicine, China Medical University, Taichung, Taiwan, 402.
Nou-Ying
NY
Tang
Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, 404.
Shu-Fen
SF
Peng
Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, 404.
Wen-Wen
WW
Huang
Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, 404.|Department of Biotechnology, Asia University, Taichung, Taiwan, 413.
Jing-Gung
JG
Chung
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002193:Cantharidin / Q000627:therapeutic use / Q000633:toxicity*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056741:Cyclin D / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017382:Reactive Oxygen Species / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D056741:Cyclin D; D017382:Reactive Oxygen Species; D053218:Receptors, Death Domain; D053221:TNF-Related Apoptosis-Inducing Ligand; D045304:Cytochromes c; D020169:Caspases; D002193:Cantharidin
apoptosis; cantharidin; cell cycle; human skin cancer cells