<p>α-Hederin Increases The Apoptosis Of Cisplatin-Resistant Gastric Cancer Cells By Activating Mitochondrial Pathway In Vivo And Vitro</p>

Abstract

IntroductionGastric cancer remains an important cancer worldwide, and conventional chemotherapeutic drugs have the defects of drug resistance and cell toxicity. α-Hederin has been found to have certain therapeutic effects on various types of human cancers. However, studies on the α-hederin that exert biological activities on the cisplatin-resistant gastric cancer cells are limited. In this study, we evaluated the effects of α-hederin in HGC27/DDP and the potential mechanisms both in vivo and in vitro.MethodsHGC27/DDP cells were cultured in DMEM/F12 medium. Cell proliferation and viability were assessed quantitatively using Cell Counting Kit-8. Cell invasion and migration were detected by Transwell invasion assay and wound healing assay. Cell apoptosis was examined by employing Hoechst 33258 Staining Kit and an Annexin V-PE apoptosis kit. Intracellular GSH levels were examined by using a GSH Assay Kit. DCFH-DA and JC-1 Kit were used to detect levels of intracellular reactive oxygen species (ROS) and changes in mitochondrial membrane potential (∆Ψm). The protein levels of Apaf-1, AIF, Bax, Bcl-2, Cyt C, Survivin, cleaved caspase-3, cleaved caspase-9, MMP-9 and MMP-2 were detected by Western blot analysis. The effect of α-hederin in vivo was observed by xenograft tumor models in nude mice.ResultsThe α-hederin treatment significantly inhibited the proliferation in a dose- and time-dependent manner of HGC27/DDP and induced obvious apoptosis compared with the control group (P<0.05). Meanwhile, the ability of cells to invade and migrate was suppressed (P<0.05). The α-hederin induced the depletion of GSH (P<0.05) and the accumulation of intracellular ROS (P<0.05), changed the mitochondrial membrane potential (P<0.05), increased the Bax, Apaf-1, AIF, Cyt C, cleaved caspase-3 and cleaved caspase-9 expression and decreased the protein level of Bcl-2, survivin, MMP-9 and MMP-2 (P<0.05). Pretreatment with NAC (12 mM) enhanced the tendency and pretreatment with BSO (8 mM) attenuated the tendency above (P<0.05). Meanwhile, α-hederin inhibited xenograft tumor growth in vivo (P<0.05).ConclusionOur study provides strong molecular evidence to support our hypothesis that α-hederin inhibits the proliferation and induces the apoptosis of HGC27/DDP cells by increasing the levels of intracellular ROS and triggering mitochondrial pathway activation.

Piezo type mechanosensitive ion channel component 1 facilitates gastric cancer omentum metastasis

“…Furthermore, Ψm plays a key role in cancer metastasis and angiogenesis 18 . In this study, Piezo1 activation increased the Ψm and Ca 2+ levels in GC cells 19‐21 . However, after Piezo1 interference, the Ψm and Ca 2+ levels in GC cells were significantly decreased.…”

“…18 In this study, Piezo1 activation increased the Ψm and Ca 2+ levels in GC cells. [19][20][21] However, after Piezo1 interference, the Ψm and Ca 2+ levels in GC cells were significantly decreased. Furthermore, we examined the effect of Piezo1 interference on the P53/P21 axis, a key signal of proliferation.…”

α‑hederin overcomes hypoxia‑mediated drug resistance in colorectal cancer by inhibiting the AKT/Bcl2 pathway

“…α-hederin is a typical pentacyclic triterpene saponin, and a large number of studies have shown that pentacyclic triterpene α-hederin overcomes hypoxia-mediated drug resistance in colorectal cancer by inhibiting the AKT/Bcl2 pathway saponins have a wide range of biological activities, such as antitumour, antiviral, anti-inflammatory and immunoregulatory activities (9). To date, extensive research has been carried out on the antitumour effects of α-hederin, such as inhibition of tumour cell metastasis and tumour immune evasion, and enhancement of chemotherapeutic drug sensitivity (10)(11)(12)(13)(14). Therefore, it was hypothesized that α-hederin may inhibit the expression of Bcl2 by reducing the phosphorylation of AKT, thereby overcoming hypoxia-mediated drug resistance in CRC.…”

Effects and Mechanisms of Saikosaponin D Improving the Sensitivity of Human Gastric Cancer Cells to Cisplatin

“…For example, α-hederin is one of the main components from Nigella sativa seed, which is a common Chinese traditional medicine. Liu and colleagues found that α-hederin might inhibit the proliferation and induce the apoptosis of HGC-27/DDP cells by increasing intracellular reactive oxygen species levels and activating mitochondrial pathway . β-Elemene, which is a natural novel plant-derived drug with anticancer activities, showed inhibitory effects on the metastasis of SGC-7901/ADR cells by modulating the miR-1323/Cbl-b/EGFR pathway .…”

“…Liu and colleagues found that α-hederin might inhibit the proliferation and induce the apoptosis of HGC-27/DDP cells by increasing intracellular reactive oxygen species levels and activating mitochondrial pathway. 22 β-Elemene, which is a natural novel plant-derived drug with anticancer activities, showed inhibitory effects on the metastasis of SGC-7901/ADR cells by modulating the miR-1323/Cbl-b/EGFR pathway. 23 Cardamonin, a natural chalcone, might reduce 5-fluorouracil resistance of GC cells by regulating Wnt/β-catenin pathway.…”