The effect of tubeimoside-1 on the proliferation, metastasis and apoptosis of oral squamous cell carcinoma in vitro

Tingting Wu,1–4 Hongjuan Cui,5 Yamei Xu,1–4 Quangao Du,1–4 Erhu Zhao,5 Jiangjun Cao,5 Ling Nie,1–4 Gang Fu,1–4 Aishu Ren1–3,6 1College of Stomatology, Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Oral Implantology, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 5State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, People’s Republic of China; 6Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Background: Tubeimoside-1 (TBMS1), a triterpenoid saponin extracted from traditional Chinese medicine tubeimoside, exerts a cytotoxic effect on several human cancer cell lines. However, no study has focused on whether TBMS1 works on oral squamous cell carcinoma (OSCC). Materials and methods: We treated OSCC cells with TBMS1 to detect the effect and relevant molecular basis of TBMS1 for the first time. We chose two oral cancer cell lines, CAL27 and SCC15, for this study. First, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide assay and cell proliferation 5'-bromo-2'-deoxyuridine assay were carried out to detect cell growth. Second, colony formation assay was performed to assess clonogenesis capacity. Next apoptosis was analyzed by flow cytometry. Subsequently, wound healing and transwell assays were applied to explore cell migration. Finally, Western blot was further performed to examine corresponding proteins’ expression change. Results: Our data showed that TBMS1 significantly suppressed proliferation of OSCC cells in a dose- and time-dependent manner and it inhibited migration of OSCC cells as well. After treatment with TBMS1, OSCC cells underwent cell apoptosis. Furthermore, Western blot demonstrated that TBMS1 downregulated apoptosis-associated proteins such as PARP, p-ERK1/2, Bcl-2, caspase-3, caspase-7 and caspase-8 and upregulated cleaved PARP, cleaved caspase-3 and cleaved caspase-9. It could also reduce expression of c-Myc and MMP-7. Meanwhile, TBMS1 did not change the total ERK1/2 expression. Conclusion: These results revealed that TBMS1 might be a potential chemotherapeutic drug for the management of OSCC. Keywords: tubeimoside-1, chemotherapeutic drug, oral squamous cell carcinoma, OSCC, apoptosis, underlying mechanis