Anticancer effects of veratramine via the phosphatidylinositol-3-kinase/serine-threonine kinase/mechanistic target of rapamycin and its downstream signaling pathways in human glioblastoma cell lines

• Published in: Life sciences (1973) 2022-01, Vol.288, p.120170-120170, Article 120170
• Main Authors: Kim, Daehwan, Kwon, Wookbong, Park, Song, Kim, Wansoo, Park, Jin-Kyu, Han, Jee Eun, Cho, Gil-Jae, Yun, Sungho, Han, Se-Hyeon, Kim, Myoung Ok, Ryoo, Zae Young, Choi, Seong-Kyoon
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Anticancer properties; Antitumor activity; Apoptosis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cell Cycle; Cell growth; Cell lines; Cell Movement; Cell Proliferation; Chemical compounds; Cholecystokinin; Cyclin-dependent kinase inhibitor p21; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Cytotoxicity; Downstream effects; Evaluation; Flow cytometry; G1 phase; Gene Expression Regulation, Neoplastic - drug effects; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - pathology; Glioma; Human glioblastoma cell line; Humans; Invasiveness; Kinases; MDM2 protein; Mdm2/p53/p21; mRNA; Neoplasm Invasiveness; p53 Protein; Pharmacology; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; PI3K/Akt/mTOR; Prostate; Protein-serine/threonine kinase; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-mdm2 - genetics; Proto-Oncogene Proteins c-mdm2 - metabolism; Rapamycin; Signal transduction; Signaling; Sonic hedgehog; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; Toxicity; Tumor Cells, Cultured; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Veratramine; Veratrum Alkaloids - pharmacology; Western blotting
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.120170

Antitumor effects of veratramine in prostate and liver cancers has been investigated, but it is still unclear whether veratramine can be used as an effective therapeutic agent for glioma. The aim of this study was to evaluate the potential pharmacological mechanism of veratramine in glioma. Using four types of human glioblastoma cell lines, including A172, HS-683, T98G, and U-373-MG the dose-dependent antitumor effect of veratramine was evaluated. The cytotoxicity and cell proliferation were examined by CCK-8, and cell proliferation was further confirmed by anchorage-independent colony formation assay. The cell cycle distribution and apoptotic rate was assessed by flow cytometry, and apoptosis was further evaluated by apoptosis assay. The migration and invasiveness capacity were analyzed by using transwell. Protein and mRNA levels of related factors were determined by western blotting and RT-qPCR, respectively. Veratramine markedly induced apoptosis, suppressed the cell proliferation via the cell cycle G0/G1 phase arrest, and reduced the capacity for the migration and invasion in human glioblastoma multiforme cell lines. Moreover, veratramine was sufficient to affect the phosphatidylinositol-3-kinase/serine-threonine kinase/mechanistic target of rapamycin signaling pathway and its downstream Mdm2/p53/p21 pathway in human glioblastoma cell lines. Antitumor effects of veratramine in suppression of glioma progression was mediated by the regulation of PI3K/Akt/mTOR and Mdm2/p53/p21 signaling pathway. [Display omitted]