title: Plancitoxin I from the venom of crown-of-thorns starfish (Acanthaster planci) induces oxidative and endoplasmic reticulum stress associated cytotoxicity in A375.S2 cells.
abstract: The crown-of-thorns starfish Acanthaster planci is a venomous starfish whose venom provokes strong cytotoxicity. In the present study, the purified cytotoxic toxin of A. planci venom (CAV) was identified as plancitoxin I protein by mass spectrum analyses. This study aims to investigate the molecular mechanism underlying the cytotoxicity function of plancitoxin I by focusing on the oxidative stress, mitochondrial dysfunction and endoplasmic reticulum (ER) stress pathway in human melanoma A375.S2 cells. The results indicated that after being treated with CAV toxin, A375.S2 cells significantly decreased viability in a dose-dependent manner. The CAV was found to reduce the cellular antioxidant enzymes such as SOD and CAT, and there was a significant decrease in total thiol level and mtDNA integrity, and it enhanced the lipid peroxidation. In addition, CAV increased cytosolic Ca(2+) concentration, and enhanced the expression of the ER molecular chaperones GRP78 and CHOP in a dose-dependent manner. CAV significantly elevated the activity of caspase-3, -8 and -9, and reduced the ratio of Bcl-2/Bax. The cells exhibited apoptosis were determined by using propidium iodide (PI) staining of DNA fragmentation (sub-G1 peak). In summary, the results demonstrated that plancitoxin I inhibits the proliferation of A375.S2 cells through induction of oxidative stress, mitochondrial dysfunction and ER stress associated apoptosis.
authors.affiliation: Department of Food Science and Center of Excellence for the Ocean, National Taiwan Ocean University. 2 Pei-Ning Road, Keelung 202, Taiwan, ROC.
authors.forename: Chi-Chiu
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Penghu Marine Biology Research Center, Fishery Research Institute, Council of Agriculture, Magong, Penghu 880, Taiwan, ROC.
authors.forename: Hernyi Justin
authors.initials: HJ
authors.lastname: Hsieh
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, 500, Lioufeng Road, Wufeng, Taichung 413, Taiwan, ROC.
authors.forename: Cheng-Hong
authors.initials: CH
authors.lastname: Hsieh
authors.affiliation: Department of Food Science and Center of Excellence for the Ocean, National Taiwan Ocean University. 2 Pei-Ning Road, Keelung 202, Taiwan, ROC; Department of Health and Nutrition Biotechnology, Asia University, 500, Lioufeng Road, Wufeng, Taichung 413, Taiwan, ROC. Electronic address: dfhwang@mail.ntou.edu.tw.
authors.forename: Deng-Fwu
authors.initials: DF
authors.lastname: Hwang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D053938:DNA Fragmentation; D004272:DNA, Mitochondrial / Q000737:chemistry; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D008387:Marine Toxins / Q000494:pharmacology*; D008545:Melanoma / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D013215:Starfish / Q000737:chemistry*; D014688:Venoms / Q000737:chemistry / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D004272:DNA, Mitochondrial; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D008387:Marine Toxins; D014688:Venoms; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9
keywords: A375.S2 cell; Crown-of-thorns starfish Acanthaster planci; Endoplasmic reticulum (ER) stress; Oxidative stress; Plancitoxin I