<p>Baohuoside I via mTOR Apoptotic Signaling to Inhibit Glioma Cell Growth</p>

Abstract

Introduction Baohuoside I, a novel oncotherapeutic agent, has been reported to have anti-cancer effects on a variety of cancers, but its role in glioma and its molecular mechanism are still unclear. Methods The proliferation of U251 cells was detected by real-time cellular analysis (RTCA), CCK-8, Ki67 immunofluorescence and colony formation assay. The effect of Baohuoside I on the invasion and migration of U251 cells was measured by transwell and scratch tests. The apoptosis of U251 cells was detected by flow cytometry. The expression level of related protein was detected by western blotting. Results Baohuoside I could inhibit the proliferation of human glioma cells and induce apoptosis. Further study showed that the migration and invasion ability of glioma was significantly decreased by Baohuoside I. Western blot revealed the expression of p-AMPKα1 protein was up-regulated, and the expression of p-mTOR and p-S6K was down-regulated after Baohuoside I treatment. Tumorigenesis in nude mice showed that Baohuoside I had an anti-glioma effect in vivo. Conclusion We propose a natural product, which can inhibit the proliferation, invasion and migration of glioma and may be a valuable anti-tumor candidate. The inhibitory effect of Baohuoside I on the glioma is achieved by inducing the apoptosis of the tumor cells, rather than autophagy. In addition, the pathway to induce cell apoptosis of Baohuoside I is to target the mTOR signal.

Icariside II: Anticancer Potential and Molecular Targets in Solid Cancers

“…There is much evidence indicating that Icariside II exerts apoptosis-inducing effects in various cancer cell lines ( Table 1 ; Figure 2 ). After exposure to Icariside II, the expression of cleavage of caspase-3/8/9/7/PARP and Bax increases in concentration- and time-dependent manners, but the antiapoptotic factor BCL-2 was decreased in human liver cancer cell lines ( Guo et al, 2020a ). In prostate cancer, Icariside II was shown to activate caspase-3, promote cytochrome c release into cytosol, and simultaneously reduce the expression of the inactive, proenzymatic form of caspase-9 ( Lee et al, 2009 ).…”

“…Accumulating evidence is indicating that Icariside II has the ability to control cancer cell invasion and migration in lung cancer ( Song et al, 2017 ), hepatocellular carcinoma ( Guo et al, 2020a ), cervical cancer ( Sun et al, 2020b ), osteosarcoma ( Choi et al, 2008 ), melanoma ( Peng and Zhang, 2018 ), and prostate cancer ( Li et al, 2020 ). In hepatocellular carcinoma ( Guo et al, 2020b ) and cervical cancer ( Sun et al, 2020a ), it has been demonstrated that Icariside II could weaken the migratory and invasive ability of HuH-7, HepG2, and HeLa cells through inhibiting metastasis-related protein MMP2/9 expression.…”

“…The anticancer potential of Icariside II has also been demonstrated in in vivo investigations. Nude mice xenografts, established using HCC cells, were treated with 25 mg/kgd Icariside II for 30 days and exhibited a remarkable reduction in tumor volume, weight, and the protein levels of MMP2/9 and BCL-2/Bax ratio compared to the DMSO-treated group ( Guo et al, 2020a ). The antitumor effects of Icariside II on reducing tumor weight and volume have been verified in other animal models such as HeLa-bearing mice ( Sun et al, 2020a ), sarcoma-180 tumor ICR mice ( Geng et al, 2014 ), M14 xenograft B-NSG nude mice ( Peng and Zhang, 2018 ), a U251 human xenograft model ( Guo et al, 2020b ), BALB/c mice with four T 1 -Neu cells ( Zhou et al, 2011 ), and an Eca109 xenograft model ( Wang et al, 2011 ).…”

“…The antitumor effects of Icariside II on reducing tumor weight and volume have been verified in other animal models such as HeLa-bearing mice ( Sun et al, 2020a ), sarcoma-180 tumor ICR mice ( Geng et al, 2014 ), M14 xenograft B-NSG nude mice ( Peng and Zhang, 2018 ), a U251 human xenograft model ( Guo et al, 2020b ), BALB/c mice with four T 1 -Neu cells ( Zhou et al, 2011 ), and an Eca109 xenograft model ( Wang et al, 2011 ). In these reports, the anticancer efficiency of Icariside II is achieved through inhibiting cellular proliferation ( Geng et al, 2014 ), enhancing cell apoptosis ( Guo et al, 2020a ), blocking the cell cycle ( Wang et al, 2011 ), and modifying the inflammatory microenvironment ( Zhou et al, 2011 ). The detailed information is presented in Table 3 .…”