title: Oxalicumone A, a new dihydrothiophene-condensed sulfur chromone induces apoptosis in leukemia cells through endoplasmic reticulum stress pathway.
abstract: Oxalicumone A (POA1), a novel dihydrothiophene-condensed sulfur chromone isolated from the marine fungus Penicillium oxalicum SCSGAF 0023, showed cytotoxicity against several cancer cells previously. In this study, its anti-cancer activity and underlying mechanism of this action were investigated in leukemia cells like KG-1a, HL60, U937, and K562. The results showed that POA1 inhibited dose-/time-dependently cell growth and induced apoptosis in leukemia cells. Also, POA1 caused cleavages of caspase-3, 8, 9 and PARP1, loss of mitochondrial membrane potential, up-regulations of phosphorylated p38 and JNK, and activation of endoplasmic reticulum stress (ER stress). Furthermore, 4-PBA (an ER stress inhibitor) but not SP600125 and SB203580 (JNK and p38 inhibitor, respectively) could largely inhibit POA1-induced growth suppression. Additionally, 4-PBA obstructed mitochondrial depolarization and cleavage of PARP1. These data suggested that ER stress pathway might be an important mediator in POA1-induced apoptosis. In conclusion, POA1 may have antitumor effects in leukemia cells through the induction of ER stress pathway.
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, RNAM Center for Marine Microbiology, Guangdong Key Laboratory of Marine Material Medical, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, 601 West Huangpu Road, Guangzhou 510632, China.
authors.forename: Qiao-Li
authors.initials: QL
authors.lastname: Wang
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, RNAM Center for Marine Microbiology, Guangdong Key Laboratory of Marine Material Medical, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
authors.forename: Xu-Hua
authors.initials: XH
authors.lastname: Nong
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, RNAM Center for Marine Microbiology, Guangdong Key Laboratory of Marine Material Medical, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, RNAM Center for Marine Microbiology, Guangdong Key Laboratory of Marine Material Medical, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
authors.forename: Xin-Ya
authors.initials: XY
authors.lastname: Xu
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, RNAM Center for Marine Microbiology, Guangdong Key Laboratory of Marine Material Medical, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China; South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, Guangzhou 510301, China. Electronic address: shuhuaqi@scsio.ac.cn.
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Qi
authors.affiliation: Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, 601 West Huangpu Road, Guangzhou 510632, China.
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002867:Chromones / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D013876:Thiophenes / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D002867:Chromones; D013876:Thiophenes; C000614527:oxalicumone A
keywords: Apoptosis; ER stress; Leukemia cell; MAPKs; Mechanism of action; Oxalicumone A