title: Cantharidin impairs cell migration and invasion of A375.S2 human melanoma cells by suppressing MMP-2 and -9 through PI3K/NF-κB signaling pathways.
abstract: Cancer metastasis is the major cause of cancer patient death. Melanoma is a highly important metastasis in human cancer. Cantharidin (CTD), identified as an active component of natural mylabris (Mylabris phalerata Pallas), induces apoptosis in many human cancer cells. In the present study, we investigated the anti-metastasis effects of CTD in human melanoma cancer A375.S2 cells. Flow cytometry was used to measure CTD-induced cytotoxic effects in A375.S2 cells. Wound healing assay indicated that CTD suppressed the migration of A375.S2 cells in a dose-dependent manner. The Matrigel Transwell Assay was used for cell migration and invasion examination and the results showed that CTD inhibited both. Gelatin zymography was used to investigate the activities of MMP-2/9 and the results indicated that CTD inhibited the enzymatic activities of MMP-2/9 in A375.S2 cells. The protein expression of A375.S2 cells following incubation with CTD was examined by western blotting and the results showed that CTD decreased the expression of ERK1/2, PI3K, FAK, MMP-2, -9, COX-2, NF-κB p65, TIMP 1, TIMP 2, VEFG, uPA, Rho A, GRB2, ROCK-1 and Ras, but increased the expressions of p38, JNK, p-c-jun and PKC. Based on those observations, we suggest that CTD may be used as a novel anti-cancer metastasis agent of human melanoma cancer in the future.
authors: Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan, R.O.C. General Education Center, Chienkuo Technology University, Changhua, Taiwan, R.O.C.
authors: Bin-Chuan
authors: BC
authors: Ji
authors: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C. Department of Dermatology, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C.
authors: Yu-Ping
authors: YP
authors: Hsiao
authors: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C. Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C.
authors: Chung Hung
authors: CH
authors: Tsai
authors: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.
authors: Shu-Jen
authors: SJ
authors: Chang
authors: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C.
authors: Shu-Chun
authors: SC
authors: Hsu
authors: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C.
authors: Hsin-Chung
authors: HC
authors: Liu
authors: Department of Physiology, China Medical University, Taichung, Taiwan, R.O.C.
authors: Yi-Ping
authors: YP
authors: Huang
authors: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C. jgchung@mail.cmu.edu.tw jclien@mail.cmu.edu.tw.
authors: Jin-Cherng
authors: JC
authors: Lien
authors: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C. Department of Biotechnology, Asia University, Wufeng, Taichung, Taiwan, R.O.C. jgchung@mail.cmu.edu.tw jclien@mail.cmu.edu.tw.
authors: Jing-Gung
authors: JG
authors: Chung
mesh_terms: D002193:Cantharidin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects; D008545:Melanoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D002193:Cantharidin
keywords: Cantharidin; PI3K/NF-κB signaling pathways; human melanoma cancer A375.S2 cells; invasion; migration