title: Anthraquinone G503 induces apoptosis in gastric cancer cells through the mitochondrial pathway.
abstract: G503 is an anthraquinone compound isolated from the secondary metabolites of a mangrove endophytic fungus from the South China Sea. The present study elucidates the anti-tumor activity and the underlying mechanism of G503. Cell viability assay performed in nine cancer cell lines and two normal cell lines demonstrated that the gastric cancer cell line SGC7901 is the most G503-sensitive cancer cells. G503 induced SGC7901 cell death via apoptosis. G503 exposure activated caspases-3, -8 and -9. Pretreatment with the pan-caspase inhibitor Z-VAD-FMK and caspase-9 inhibitor Z-LEHD-FMK, but not caspase-8 inbibitor Z-IETD-FMK, attenuated the effect of G503. These results suggested that the intrinsic mitochondrial apoptosis pathway, rather than the extrinsic pathway, was involved in G503-induced apoptosis. Furthermore, G503 increased the ratio of Bax to Bcl-2 in the mitochondria and decreased the ratio in the cytosol. G503 treatment resulted in mitochondrial depolarization, cytochrome c release and the subsequent cleavage of caspase -9 and -3. Moreover, it is reported that the endoplasmic reticulum apoptosis pathway may also be activated by G503 by inducing capase-4 cleavage. In consideration of the lower 50% inhibitory concentration for gastric cancer cells, G503 may serve as a promising candidate for gastric cancer chemotherapy.
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Junting
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Ye
authors.affiliation: Key Laboratory of Functional Molecules from Marine Microorganisms (Sun Yat-sen University), Department of Education of Guangdong Province, Guangzhou, Guangdong Province, China.
authors.forename: Hanxiang
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Functional Molecules from Marine Microorganisms (Sun Yat-sen University), Department of Education of Guangdong Province, Guangzhou, Guangdong Province, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: She
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China; China Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong Province, China.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China; Key Laboratory of Functional Molecules from Marine Microorganisms (Sun Yat-sen University), Department of Education of Guangdong Province, Guangzhou, Guangdong Province, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Yang
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000880:Anthraquinones / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; 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; D061945:Caspase Inhibitors / Q000494:pharmacology; D053471:Caspases, Initiator / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004718:Saccharomycetales / Q000737:chemistry; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000819:agonists / Q000235:genetics / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000880:Anthraquinones; D000970:Antineoplastic Agents; C494826:BAX protein, human; C000595707:BCL2 protein, human; D061945:Caspase Inhibitors; C000598474:G503 compound; D009842:Oligopeptides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C403753:benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone; C403754:benzyloxycarbonyl-leucyl-glutamyl-histidyl-aspartic acid fluoromethyl ketone; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C093516:CASP4 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D053471:Caspases, Initiator