title: Induction of human chronic myeloid leukemia K562 cell apoptosis by virosecurinine and its molecular mechanism.
abstract: Virosecurinine is a major alkaloid of the plant Securinega suffruticosa and has been found to be a potent agent in inducing the differentiation of cancer cells. The present study aimed to investigate the antitumor effects of virosecurinine by inducing the apoptosis of leukemic K562 cells and to examine the underlying mechanisms. K562 cells were treated with different concentrations of virosecurinine (6.25, 12.5, 25, 50, 100 and 200 µmol/l) for 24, 48 and 72 h. The cell counting kit (CCK)‑8 method was used to detect the antitumor effect of K562 cells in vitro. Flow cytometry was used to observe the apoptotic ratio and analyze the cell cycle following treatment with virosecurinine in K562 cells. Light and electron microscopy was used to identify morphological alterations in the virosecurinine‑treated K562 cells. The mRNA levels of mammalian target of rapamycin (mTOR), SH2 domain‑containing inositol‑5'‑phosphatase 2 (SHIP2), phosphatase and tensin homologue (PTEN) and breakpoint cluster region (BCR)/Abelson (ABL) were detected pre and post‑virosecurinine treatment using reverse transcription quantitative polymerase chain reaction (RT‑qPCR). The generation depression effects of K562 cells cultured in vitro were detected using CCK‑8 technology, which revealed a dose and time‑dependent association. The IC50 was 32.984 µmol/l at 48 h. Flow cytometric analysis indicated that treatment with virosecurinine at concentrations of 6.25, 25 and 50 µmol/l increased the apoptotic rate of the K562 cells and caused G1/S phase arrest. RT‑qPCR indicated that virosecurinine upregulated the gene expression of PTEN and downregulated the expression of mTOR, SHIP‑2 and BCR/ABL in K562 cells. Virosecurinine inhibited the growth and proliferation of the K562 cell lines and induced apoptosis in K562 cells by affecting the expression of mTOR, SHIP2, BCR/ABL and PTEN.
authors.affiliation: Department of Oncology, Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
authors.forename: Maidong
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Oncology, Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Medical Oncology, The Cancer Center, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
authors.forename: Dongyun
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Wencai
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Medical Oncology, The Cancer Center, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
authors.forename: Zhaoning
authors.initials: Z
authors.lastname: Ji
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001381:Azepines / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D020014:K562 Cells; D007783:Lactones / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D001381:Azepines; D007783:Lactones; D010880:Piperidines; C012607:virosecurinine; C546842:MTOR protein, human; D016044:Fusion Proteins, bcr-abl; D058570:TOR Serine-Threonine Kinases; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases