title: Tanshinone IIA inhibits human gastric carcinoma AGS cell growth by decreasing BiP, TCTP, Mcl‑1 and Bcl‑xL and increasing Bax and CHOP protein expression.
abstract: Tanshinone IIA (Tan-IIA) is extracted from Danshen (Salviae Miltiorrhizae Radix) and is a natural anti-cancer agent, which possesses antitumor activity in a variety of human cancer cells. Tan-IIA can induce apoptosis and inhibit the proliferation of gastric cancer through different molecular mechanisms. However, the efficacy and molecular mechanism of Tan-IIA in gastric cancer have not been well studied. In the present study, the cytotoxicity of Tan-IIA in human gastric cancer AGS cells by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide assay was examined. The protein expression levels of B-cell lymphoma-extra large (Bcl-xL), Bcl-2-associated X protein (Bax), myeloid cell leukemia 1 protein (Mcl-1), translationally-controlled tumor protein (TCTP), binding immunoglobulin protein (BiP), calnexin, protein kinase-like endoplasmic reticulum kinase, eIF2α, activating transcription factor 4 (ATF4), inositol-requiring enzyme 1α (IRE1α), ATF6, caspase-12, caspase-9, caspase-3, C/EBP-homologous protein (CHOP) and β-actin in AGS cells were measured by western blot analysis. The results showed that Tan-IIA inhibited AGS cells in a time-and dose-dependent manner. AGS cells treated with Tan-IIA upregulated the protein expression of caspase-12, caspase-9, caspase--3, CHOP and Bax, but downregulated the protein expression of BiP, TCTP, Mcl-1 and Bcl-xL. These findings indicated that Tan-IIA inhibits the growth of human gastric cancer AGS cells. One of the molecular mechanisms may be through decreasing the protein expression of BiP to induce the activation of endoplasmic reticulum stress, followed by increasing the protein expression of caspase-12 to upregulate CHOP expression. The other may be through decreasing the protein expression of Mcl-1, Bcl-xL and TCTP, but increasing Bax, caspase-9 and caspase-3 to induce apoptosis. The chemotherapeutic potential of Tan-IIA for human gastric cancer warrants further study in the future.
authors.affiliation: Tumor Research Center of Integrative Medicine, Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C.
authors.forename: Chin-Cheng
authors.initials: CC
authors.lastname: Su
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D051742:Transcription Factor CHOP / Q000378:metabolism*; D000090324:Tumor Protein, Translationally-Controlled 1; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D014408:Biomarkers, Tumor; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C021751:tanshinone; D051742:Transcription Factor CHOP; D020169:Caspases