<p>Polyphyllin VI induces apoptosis and autophagy in human osteosarcoma cells by modulation of ROS/JNK activation</p>

Abstract

PurposePolyphyllin VI, a main active saponin isolated from traditional medicinal plant Paris polyphylla, has exhibited antitumor activities in several cancer cell lines. In the present study, we investigated the antitumor effect of Polyphyllin VI against human osteosarcoma cells (U2OS) and the underlying molecular mechanisms.MethodsThe U2OS cell lines were used to determine the antiproliferative effect of Polyphyllin VI by CCK8 assay. Cell cycle was analyzed by flow cytometry. The Polyphyllin VI-induced apoptosis was determined by Annexin V-APC/7-AAD apoptosis detection kit and JC-1 staining. Meanwhile, the autophagy was determined by acridine orange staining. The apoptosis and autophagy-related proteins were monitored by Western blot assay. Subsequently, intracellular hydrogen peroxide (H2O2) and the activation of ROS/JNK pathway were detected.ResultsPolyphyllin VI could potently inhibit cell proliferation by causing G2/M phase arrest. Polyphyllin VI induced mitochondria-mediated apoptosis with the upregulation of proapoptotic proteins Bax and poly ADP-ribose polymerase, and downregulation of antiapoptotic protein Bcl-2 in U2OS cells. Concomitantly, Polyphyllin VI provoked autophagy with the upregulation of critical Atg proteins and accumulation of LC3B-II. Intracellular H2O2 production was triggered upon exposure to Polyphyllin VI, which could be blocked by ROS scavenger. Polyphyllin VI dramatically promoted JNK phosphorylation, whereas it decreased the levels of phospho-p38 and ERK.ConclusionOur results reveal that Polyphyllin VI may effectively induce apoptosis and autophagy to suppress cell growth via ROS/JNK activation in U2OS cells, suggesting that Polyphyllin VI is a potential drug candidate for the treatment of osteosarcomas.

<p>Polyphyllin VI Induces Apoptosis and Autophagy via Reactive Oxygen Species Mediated JNK and P38 Activation in Glioma</p>

“…In this study, we found that PPVI could activate the JNK and p38 pathways, consistent with previous studies. 6,20 Furthermore, SP and SB partially attenuated the PPVIinduced effects on glioma cells, and NAC treatment attenuated JNK and p38 activation induced by PPVI. However, the levels of ROS, after SP and SB treatment, did not show an obvious change indicating that ROS could modulate the JNK and p38 pathways.…”

“…15 In the current study, we describe the ability of PPVI, the main active ingredient extracted from Paris polyphylla, to exhibit cytotoxicity in various malignancies. 6,20,23,24 We reveal the anti-tumor effects of this compound, in the suppression of cell proliferation and migration, blocking cell cycle progression as well as the induction of autophagy and apoptosis. Furthermore, we show that the anti-tumor activity of PPVI in glioma cells function through the accumulation of ROS and activation of the JNK and p38 pathways.…”

“…Previous studies suggest that excessive ROS production can induce both apoptosis and autophagy. 14,20,21 Excess ROS production can upregulate apoptosis-related proteins and induce apoptosis. Based on this hypothesis, we investigated the association between PPVI treatment and ROS production in glioma cells using DCFH-DA, a fluorescence probe.…”

Neferine induces apoptosis by modulating the ROS‑mediated JNK pathway in esophageal squamous cell carcinoma

“…Recent studies have shown that ROS accelerates the death of tumor cells, thereby effectively treating cancer (38,39). High production of ROS decreases the mitochondrial transmembrane potential and the release of cytochrome c, which then activates a series of caspases, thereby inducing cell apoptosis.…”

<p>Genetic and Clinical Characterization of HOXB2 in Glioma</p>

“…Glioma is characterized by rapid proliferation and high invasiveness that pose difficulties for treatment. 16,17 Previous studies demonstrated that different subtypes of glioma exhibited significant differences in treatment and prognosis. 2,[18][19][20] Identification of effective markers that can predict the prognosis of glioma patients is essential for the development of successful treatment plans.…”