Chili peppers are loved by people all over the world and have been indispensable vegetable for three meals a day. However, reports about the association between chili consumption and gastric cancer (GC) risk have been conflicting. So, we carried out this meta-analysis to evaluate the effect of chili consumption on the risk of GC. Medline, PubMed, Web of science, Embase, Cochrane Library databases were systematically searched until May 2019. Heterogeneity among studies was examined using Q and I² statistics. Combined odds ratio (OR) with their 95% confidence interval (CI) were calculated using a random- or fixed-effects model. All data were analyzed using STATA 15.1 software. 13 studies (3,095 cases and 4,761 controls) were included in the meta-analysis. A 1.96-fold increased risk of GC was shown for the moderate-high chili consumption (OR = 1.96, 95%CI =1.59−2.42). Dose-response analysis showed a significant nonlinear association of GC risk with capsaicin intake (p_{non-linearity} <0.05) and suggested a significant positive association between high chili consumption and GC risk (OR = 2.28, 95%CI = 1.76–2.96) but not moderate chili consumption (OR = 0.72, 95%CI = 0.36–1.41). Sensitivity analysis and publication bias test results indicated that no publication bias and the results were reliable (Egger’s: P = 0.288). Evidence from this meta-analysis suggested that a higher level of chili consumption may be associated with an increased incidence of GC. More studies are warranted to confirm the association between chili consumption and the risk of GC.

Cisplatin (DDP)‐based chemotherapy is a preferred treatment for a broad spectrum of cancers, but the precise mechanisms of its hepatotoxicity are not yet clear. Recently, the role of voltage‐dependent anion channel protein 1 (VDAC1) in mitochondrial activity and cell apoptosis has attracted much attention. Our aim was to investigate the effects of mitochondrial outer membrane protein VDAC1 oligomerization in DDP‐induced hepatocyte apoptosis. L‐02 hepatocytes were divided into 4 groups: (a) control group, (b) 4,4'diisothiocyanate‐2,2'‐disulfonic acid (DIDS; 40 μm) group, (c) DDP (5 μm) group, and (d) DDP and DIDS combination group. Cell apoptosis was tested by Annexin V/FITC assay, protein expression of caspase‐3, γH2AX and NDUFB6 were observed by western blot assay, reactive oxygen species (ROS), and mitochondrial superoxide anion radical (O₂^•−) were detected by DCFH‐DA and MitoSOX probe, and DNA damage was assessed by comet assay. Moreover, the activity of mitochondrial respiratory chain complex I was determined by the colorimetry method. Compared with the control group, apoptosis rate and activated cleaved‐caspase‐3 protein, ROS and O₂^•− generation, DNA damage marker comet tail length, and γH2AX protein level increased in the DDP treatment group (P < 0.05). Activity of mitochondrial COXI decreased after DDP treatment (P < 0.05). DIDS, as a VDAC1 oligomerization inhibitor, antagonized DDP‐induced apoptosis by diminishing oxidative stress and DNA damage and protecting mitochondrial complex protein. These results show that VDAC1 oligomerization may play an important role in DDP‐induced hepatocyte apoptosis by increasing ROS and mtDNA leakage from VDAC1 pores, exacerbating oxidative stress and mtDNA damage.

Cisplatin is one of the most effective anti-cancer drugs, but its efficacy is limited by the development of resistance. Previous studies have shown that mitochondria play critical roles in cisplatin cytotoxicity, however, the exact mechanism of mitochondria involved in cisplatin sensitivity has not been clarified. In this study, cisplatin triggered mitochondrial oxidative stress and the decrease of mitochondria membrane potential in human cervical cancer cells. Then we screened a series of mitochondrial relevant inhibitors, including mitochondrial mPTP inhibitors DIDS and CsA, and mitochondrial respiratory complex inhibitors Rot and TTFA. Among these, only DIDS, as the inhibitor of mitochondrial outer membrane protein VDAC1, showed strong antagonism against cisplatin toxicity. DIDS mitigated cisplatin-induced MFN1-dependent mitochondrial fusion, mitochondrial dysfunction and oxidative damage. These findings demonstrated that VDAC1 may serve as a potential therapeutic target in the increase sensitivity of cisplatin, which provides an attractive pharmacological therapy to improve the effectiveness of chemotherapy.