title: Dodecyl gallate induces apoptosis by upregulating the caspase-dependent apoptotic pathway and inhibiting the expression of anti-apoptotic Bcl-2 family proteins in human osteosarcoma cells.
abstract: Dodecyl gallate (DG) is a gallic acid ester that has been shown to inhibit tumor growth. The aim of this study was to investigate the mechanism by which DG induces antiproliferative and apoptotic effects in MG-63 human osteosarcoma cells. Dose- and time-dependent cytotoxic effects of DG were determined using an MTT assay. The results showed that the half-maximal inhibitory concentration (IC50) of DG in MG-63 cells was 31.15 µM at 24 h, 10.66 µM at 48 h, and 9.06 µM at 72 h. Flow cytometric analysis demonstrated that exposure to 20 and 40 µM DG resulted in an increase in the sub-G1 phase population and in S-phase cell cycle arrest. Furthermore, western blot analysis of apoptosis-related protein expression revealed an increase in the activation of caspases 8 and 3, cleavage of poly (ADPribose) polymerase (PARP), and disruption of mitochondrial membrane permeability was measured by flow cytometry. An increase in the Bax/Bcl-2 ratio and a decrease in the expression of inhibitor of apoptosis protein (IAP) family members, namely X-linked inhibitor of apoptosis protein and survivin, were also observed following DG treatment. These data provide insight into the molecular mechanisms governing the ability of DG to induce apoptosis in human osteosarcoma cells in vitro.
authors.affiliation: Orthopedics & Sports Medicine Laboratory, Changhua Christian Hospital, Changhua 500‑06, Taiwan, R.O.C.
authors.forename: Chun-Hsiang
authors.initials: CH
authors.lastname: Cheng
authors.affiliation: Division of Neurosurgery, Department of Surgery, Changhua Christian Hospital, Changhua 500‑06, Taiwan, R.O.C.
authors.forename: Yen-Po
authors.initials: YP
authors.lastname: Cheng
authors.affiliation: Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua 500‑06, Taiwan, R.O.C.
authors.forename: Ing-Lin
authors.initials: IL
authors.lastname: Chang
authors.affiliation: Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua 500‑06, Taiwan, R.O.C.
authors.forename: Hsin-Yao
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua 500‑06, Taiwan, R.O.C.
authors.forename: Chia-Chieh
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua 500‑06, Taiwan, R.O.C.
authors.forename: Chen-Pu
authors.initials: CP
authors.lastname: Hsieh
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051636:X-Linked Inhibitor of Apoptosis Protein; C008259:lauryl gallate; D005707:Gallic Acid; D020169:Caspases