title: Harmine Hydrochloride Triggers G2 Phase Arrest and Apoptosis in MGC-803 Cells and SMMC-7721 Cells by Upregulating p21, Activating Caspase-8/Bid, and Downregulating ERK/Bad Pathway.
abstract: This study aimed to investigate the effects of harmine hydrochloride (HMH) on digestive tumor cells in vitro and its molecular mechanism. MTT assays showed that HMH inhibited the proliferation of some human cancer cell lines and had no obvious inhibitory effects on human LO2 cells. Flow cytometry assays showed that HMH trigged G2 phase arrest in MGC-803 cells and SMMC-7721 cells, while the expression of cyclin A, cyclin B, p21, Myt1, and p-cdc2 (Tyr15) was upregulated. Flow cytometry assays also showed that the percentages of apoptotic cells were increased, the mitochondrial transmembrane potential (ΔΨm) decreased, and the cleavage of caspase-9, caspase-3, and poly (Adenosine diphosphate ribose) polymerase (PARP) were observed, the expression of Bad increased, phospho-Bad (S112) decreased, pro-caspase-8 was cleaved, and Bid (22 kDa) was cleaved. The expression of p-ERK decreased in both cells. In conclusion, these results demonstrated that HMH upregulates the expression of p21, activates Myt1 and inhibits cdc2 by phospho-cdc2 (Y15), and triggers G2 phase arrest in both MGC-803 cells and SMMC-7721 cells. It can also activate the mitochondria-related cell apoptosis pathway through the caspase-8/Bid pathway, inhibiting the ERK/Bad pathway and promoting apoptosis in both of these two cell types.
authors.affiliation: Department of Microbiology and Immunology, Medical College, Jinan University, Guangzhou, 510630, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
authors.forename: Chun-Rong
authors.initials: CR
authors.lastname: Huang
authors.affiliation: Department of Laboratory, Foshan Fourth People's Hospital, Foshan, 528000, Guangdong Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.|Department of General Surgery, The First People's Hospital of Nanyang City, Nanyang, 473000, China.
authors.forename: Xia-Kai
authors.initials: XK
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Medical College, Jinan University, Guangzhou, 510630, China.
authors.forename: Jia-Jin
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, Medical College, Jinan University, Guangzhou, 510630, China.
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, Medical College, Jinan University, Guangzhou, 510630, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Biochemistry, Medical College, Jinan University, Guangzhou, 510630, China.
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Jiang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects*; D006247:Harmine / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D015854:Up-Regulation; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: C494819:BAD protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051025:bcl-Associated Death Protein; D006247:Harmine; C505407:CASP3 protein, human; D053148:Caspase 3; D053181:Caspase 8
keywords: ERK; apoptosis; cell cycle arrest; harmine hydrochloride