Down-regulation and nuclear localization of survivin by sodium butyrate induces caspase-dependent apoptosis in human oral mucoepidermoid carcinoma

Objective: Sodium butyrate (NaBu) is a histone deacetylase inhibitor that possesses an apoptotic ability. However, the molecular mechanism by which NaBu induces apoptosis in human oral mucoepidermoid carcinoma (MEG), a type of salivary gland tumor, remains unclear. Materials and methods: The anticancer effects of NaBu and its related molecular mechanisms were determined by trypan blue exclusion assay, 4'-6-diamidino-2-phenylindole staining, live/dead assay, human apoptosis array, RT-PCR, western blotting, immunocytochemistry, preparation of nuclear fractions, and nude mice tumor xenograft. Results: In this study, we found that NaBu inhibited growth and induced apoptosis in the human oral MEC cell lines MC3 and YD15 with acetylation of histone proteins H2A and H3. NaBu apparently down-regulated survivin protein, as evidenced by the results of the human apoptosis antibody array, and modulated it at the post-translational process. Interestingly, NaBu caused nuclear translocation of survivin protein in both cell lines. NaBu also resulted in decreased expression levels of Bcl-xL mRNA and protein, leading to induction of caspase-dependent apoptosis in human oral MEC cell lines. In addition, NaBu administration inhibited tumor growth in vivo at a dosage of 500 mg/kg/day, but it did not cause any hepatic or renal toxicity. Conclusion: This study provides new insights into the molecular mechanism of apoptotic actions by NaBu in human oral MEC and the basis of its clinical application for the treatment of human oral MEC.OAIID:RECH_ACHV_DSTSH_NO:T201831523RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A080405CITE_RATE:4.636FILENAME:09_201901_Down-regulation and nuclear localization of survivin by sodium butyrate induces caspase-dependent apoptosis in human oral mucoepidermoid carcinoma_Oral Oncology.pdfDEPT_NM:치의과학과EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/6a6ff213-581a-4354-94f3-99c233992a57/linkN

In vitro and in vivo anti-cancer activity of silymarin on oral cancer

Silymarin, a standardized extract from milk thistle fruits has been found to exhibit anti-cancer effects against various cancers. Here, we explored the anti-cancer activity of silymarin and its molecular target in human oral cancer in vitro and in vivo. Silymarin dose-dependently inhibited the proliferation of HSC-4 oral cancer cells and promoted caspase-dependent apoptosis. A human apoptosis protein array kit showed that death receptor 5 may be involved in silymarin-induced apoptosis, which was also shown through western blotting, immunocytochemistry, and reverse transcription-polymerase chain reaction. Silymarin increased cleaved caspase-8 and truncated Bid, leading to accumulation of cytochrome c. In addition, silymarin activated death receptor 5/caspase-8 to induce apoptotic cell death in two other oral cancer cell lines (YD15 and Ca9.22). Silymarin also suppressed tumor growth and volume without any hepatic or renal toxicity in vivo. Taken together, these results provide in vitro and in vivo evidence supporting the anti-cancer effect of silymarin and death receptor 5, and caspase-8 may be essential players in silymarin-mediated apoptosis in oral cancer.OAIID:RECH_ACHV_DSTSH_NO:T201815970RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A080405CITE_RATE:3.65FILENAME:7_201805_In vitro and in vivo anti-cancer activity of silymarin on oral cancer_Tumor Biology.pdfDEPT_NM:치의과학과EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/749288f3-cc73-4647-8ade-52f5475c67c1/linkY

Supplementary Material, Supplementary_Figure_1 – In vitro and in vivo anti-cancer activity of silymarin on oral cancer

<p>Supplementary Material, Supplementary_Figure_1 for In vitro and in vivo anti-cancer activity of silymarin on oral cancer by Dong-HoonWon, Lee-Han Kim, Boonsil Jang, In-Hyoung Yang, Hye-Jeong Kwon, Bohwan Jin, Seung Hyun Oh, Ju-Hee Kang, Seong-Doo Hong, Ji-Ae Shin and Sung-Dae Cho in Tumor Biology</p