Journal of Biochemical and Molecular Toxicology published new progress about Apoptosis. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, HPLC of Formula: 112-63-0.
Xue, Yu-Ye; Lu, Yun-Yang; Sun, Guang-Qiang; Fang, Fei; Ji, Yu-Qiang; Tang, Hai-Feng; Qiu, Peng-Cheng; Cheng, Guang published the artcile< CN-3 increases TMZ sensitivity and induces ROS-dependent apoptosis and autophagy in TMZ-resistance glioblastoma>, HPLC of Formula: 112-63-0, the main research area is temozolomide CN3 anticancer ROS apoptosis autophagy glioblastoma; ROS; TMZ; asterosaponin; glioblastoma; resistance; starfish Culcita novaeguineae.
Many glioma patients develop resistance to temozolomide (TMZ) treatment, resulting in reduced efficacy and survival rates. TMZ-resistant cell lines SHG44R and U87R, which highly express O6-methylguanine DNA methyltransferase (MGMT) and P-gp, were established. CN-3, a new asterosaponin, showed cytotoxic effects on TMZ-resistant cells in a dose- and time-dependent manner via reactive oxygen species (ROS)-mediated apoptosis and autophagy. Transmission electron microscopy and monodansylcadaverine (MDC) staining showed turgidity of the mitochondria and autophagosomes in CN-3-treated SHG44R and U87R cells. The autophagy inhibitor 3-methyladenine was used to confirm the important role of autophagy in CN-3 cytotoxicity in TMZ-resistant cells. The ROS scavenger N-acetyl- L-cysteine (NAC) attenuated the levels of ROS induced by CN-3 and, therefore, rescued the CN-3 cytotoxic effect on the viability of SHG44R and U87R cells by Cell Counting Kit-8 assays and JuLI-Stage videos. MDC staining also confirmed that NAC rescued an autophagosome increase in CN-3-treated SHG44R and U87R cells. Western blotting revealed that CN-3 increased Bax, cleaved-caspase 3, cytochrome C, PARP-1, LC3-II, and Beclin1, and decreased P-AKT, Bcl-2, and p62. Further rescue experiments revealed that CN-3 induced apoptosis and autophagy through ROS-mediated cytochrome C, cleaved-caspase 3, Bcl-2, P-AKT, PARP-1, and LC3-II. In addition, CN-3 promoted SHG44R and U87R cells sensitive to TMZ by reducing the expression of P-gp, MGMT, and nuclear factor kappa B p65, and it had a synergistic cytotoxic effect with TMZ. Moreover, CN-3 disrupted the natural cycle arrest and inhibited the migration of SHG44R and U87R cells by promoting cyclin E1 and D1, and by decreasing P21, P27, N-cadherin, β-catenin, transforming growth factor beta 1, and Smad2.
Journal of Biochemical and Molecular Toxicology published new progress about Apoptosis. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, HPLC of Formula: 112-63-0.
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