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

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 fo...

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Bibliographic Details
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
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Summary: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]
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2021.120170