Vitexin suppresses autophagy to induce apoptosis in hepatocellular carcinoma via activation of the JNK signaling pathway

Abstract

Vitexin, a flavonoids compound, is known to exhibit broad anti-oxidative, anti-inflammatory, analgesic, and antitumor activity in many cancer xenograft models and cell lines. The purpose of this study was to investigate the antitumor effects and underlying mechanisms of vitexin on hepatocellular carcinoma. In this study, we found that vitexin suppressed the viability of HCC cell lines (SK-Hep1 and Hepa1-6 cells) significantly. Vitexin showed cytotoxic effects against HCC cell lines in vitro by inducing apoptosis and inhibiting autophagy. Vitexin induced apoptosis in a concentration-dependent manner, and caused up-regulations of Caspase-3, Cleave Caspase-3, and a down-regulation of Bcl-2. The expression of autophagy-related protein LC3 II was significantly decreased after vitexin treatment. Moreover, western blot analysis presented that vitexin markedly up-regulated the levels of p-JNK and down-regulated the levels of p-Erk1/2 in SK-Hep1 cells and Hepa1-6 cells. Cotreatment with JNK inhibitor SP600125, we demonstrated that apoptosis induced by vitexin was suppressed, while the inhibition of autophagy by vitexin was reversed. The results of colony formation assay and mouse model confirmed the growth inhibition role of vitexin on HCC in vitro and in vivo. In conclusion, vitexin inhibits HCC growth by way of apoptosis induction and autophagy suppression, both of which are through JNK MAPK pathway. Therefore, vitexin could be regarded as a potent therapeutic agent for the treatment of HCC.

Retracted Article: Vitexin mitigates myocardial ischemia reperfusion-induced damage by inhibiting excessive autophagy to suppress apoptosis via the PI3K/Akt/mTOR signaling cascade

“…35 He's research elucidated that vitexin suppressed autophagy in hepatocellular carcinoma. 15 Whether vitexin suppressed autophagy in cardiomyocytes during MI/R was still remained unclear. In this present study, we found that vitexin treatment markedly decreased Beclin1, LC3I/II protein level and the number of GFP-LC3 dots while increased p62 protein level compared to MI/R model group, suggesting that vitexin may improve myocardial damage by inhibiting autophagy of cardiomyocytes in MI/R injury.…”

“…Aer H9c2 cells were treated with or without vitexin, the puncta formation of GFP-LC3 was determined under uorescent microscopy (Olympus BX5) as the previous study described. 15 Cells were considered to have accumulated autophagosomes when more than 5 puncta were counted.…”

Possible Epigenetic Role of Vitexin in Regulating Neuroinflammation in Alzheimer’s Disease

“…Vitexin (apigenin-8-C-glucoside) is an active component found in abundance in most medicinal plant species such as pearl millet [55], hawthorn [56], bamboo [57], and Ficus deltoidea [58]. The compound is said to possess a number of pharmacological properties including anticancer [59], antinociceptive [60], antiviral [61], anti-inflammatory [62], and anti-AD [63]. However, this review will be focusing on the anti-AD and antineuroinflammatory properties that the vitexin compound possesses.…”

Role of the MAPK/cJun NH 2 -terminal kinase signaling pathway in starvation-induced autophagy

“…This mechanism of MAPK8 signaling is mediated by BCL2 (B cell leukemia/lymphoma 2) phosphorylation (on Thr69, Ser70, and Ser87) that disrupts the interaction of BCL2 with BECN1 (beclin 1, autophagy related) and initiates BECN1-dependent autophagy [5]. Subsequent studies have provided strong support for this role of MAPK8 in autophagy [6–19], although contributing roles for MAPK9 [20–23] and alternative potential functions of MAPK8 related to autophagy have also been reported [24–29]. …”