Daehwan Kim1, Wookbong Kwon2, Song Park3, Wansoo Kim4, Jin-Kyu Park5, Jee Eun Han5, Gil-Jae Cho5, Sungho Yun5, Se-Hyeon Han6, Myoung Ok Kim7, Zae Young Ryoo8, Seong-Kyoon Choi9. 1. Core Protein Resources Center, DGIST, Daegu, Republic of Korea; Division of Biotechnology, DGIST, Daegu, Republic of Korea; School of Life Science, BK21 FOUR KNU Creative Bioresearch, Kyungpook National University, Daegu, Republic of Korea. 2. Core Protein Resources Center, DGIST, Daegu, Republic of Korea; Division of Biotechnology, DGIST, Daegu, Republic of Korea. 3. Core Protein Resources Center, DGIST, Daegu, Republic of Korea; Department of Brain and Cognitive Sciences, DGIST, Daegu, Republic of Korea. 4. Core Protein Resources Center, DGIST, Daegu, Republic of Korea; School of Life Science, BK21 FOUR KNU Creative Bioresearch, Kyungpook National University, Daegu, Republic of Korea. 5. College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea. 6. Department of News-team, SBS (Seoul Broadcasting System), Mokdongseo-ro 161, Yangcheon-gu, Seoul, South Korea; School of Media Communication, Hanyang University, Wangsimni-ro 222, Seongdonggu, Seoul, South Korea. 7. Department of Animal Science and Biotechnology, ITRD, Kyungpook National University, Sangju 37224, Republic of Korea. 8. School of Life Science, BK21 FOUR KNU Creative Bioresearch, Kyungpook National University, Daegu, Republic of Korea. Electronic address: jaewoong64@knu.ac.kr. 9. Core Protein Resources Center, DGIST, Daegu, Republic of Korea; Division of Biotechnology, DGIST, Daegu, Republic of Korea. Electronic address: cskbest@dgist.ac.kr.
Abstract
AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: Antitumor effects of veratramine in suppression of glioma progression was mediated by the regulation of PI3K/Akt/mTOR and Mdm2/p53/p21 signaling pathway.
AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: Antitumor effects of veratramine in suppression of glioma progression was mediated by the regulation of PI3K/Akt/mTOR and Mdm2/p53/p21 signaling pathway.