title: Apoptosis-like cell death induced by nematocyst venom from Chrysaora helvola Brandt jellyfish and an in vitro evaluation of commonly used antidotes.
abstract: The present work investigated the in vitro cytotoxicity of nematocyst venom (NV) from Chrysaora helvola Brandt (C. helvola) jellyfish against human MCF-7 and CNE-2 tumor cell lines. Potent cytotoxicity was quantified using the MTT assay (LC50=12.07±3.13 and 1.6±0.22μg/mL (n=4), respectively). Apoptosis-like cell death was further confirmed using the LDH release assay and Annexin V/PI double staining-based flow cytometry analysis. However, only activation of caspase-4 was observed. It is possible that some caspase-independent pathways were activated by the NV treatment. Since no reference or antivenom is available, the effects of several commonly used antidotes on the cytotoxicity of NV were examined on more sensitive CNE-2 cells to determine the appropriate emergency measures for envenomation by C. helvola. The phospholipase A2 (PLA2) inhibitor para-bromophenacyl bromide (pBPB) showed no protective effect, while Mg(2+) potentiated cytotoxicity. Voltage-gated L-type Ca(2+) channel blockers (verapamil, nifedipine and felodipine) and Na-Ca(2+) exchanger inhibitor KB-R7943 also showed no effect. Assays using Ca(2+)-free culture media or the intracellular Ca(2+) chelator BAPTA also could not inhibit the cytotoxicity. Taken together, these results suggest that PLA2 and Ca(2+) are not directly involved in the cytotoxicity of NV from C. helvola. Our work also suggests caution regarding the choice for first aid for envenomation by C. helvola jellyfish.
authors.affiliation: Engineering Lab for Endangered Medicinal Resources of Southwest China, Guangxi Medicinal Herb Garden, Nanning 530023, China. Electronic address: 239653129@qq.com.
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: Qu
authors.affiliation: Engineering Lab for Endangered Medicinal Resources of Southwest China, Guangxi Medicinal Herb Garden, Nanning 530023, China.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Pharmacology, Guangxi Medicinal University, Nanning 530021, China.
authors.forename: Zefeng
authors.initials: Z
authors.lastname: Lai
authors.affiliation: Engineering Lab for Endangered Medicinal Resources of Southwest China, Guangxi Medicinal Herb Garden, Nanning 530023, China.
authors.forename: Taozheng
authors.initials: T
authors.lastname: Zhong
authors.affiliation: Engineering Lab for Endangered Medicinal Resources of Southwest China, Guangxi Medicinal Herb Garden, Nanning 530023, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Guangxi University of Traditional Chinese Medicine, Nanning, 530200, China.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Cell Biology and Genetics, Guangxi Medicinal University, Nanning 530021, China. Electronic address: shuwei7866@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Shu
mesh_terms: D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D017209:Apoptosis; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D065096:Calcium Chelating Agents / Q000494:pharmacology*; D020169:Caspases; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003064:Cnidarian Venoms / Q000633:toxicity*; D006801:Humans; D008274:Magnesium; D037401:Scyphozoa / Q000502:physiology*
chemical_list: D000931:Antidotes; D002121:Calcium Channel Blockers; D065096:Calcium Chelating Agents; D003064:Cnidarian Venoms; D020169:Caspases; D008274:Magnesium
keywords: Antidote; Apoptosis; Ca(2+) channel blockers; Chrysaora helvola; Cytotoxicity; Nematocyst venom; PLA(2)