Atractylodin inhibited the migration and induced autophagy in cholangiocarcinoma cells via PI3K/AKT/mTOR and p38MAPK signalling pathways

Abstract

Objectives The effects of atractylodin (ATD), the bioactive compound from Atractylodes lancea, on migration and autophagy status of cholangiocarcinoma cell line were investigated. Methods Cytotoxic activity and effects on cell migration and invasion were evaluated by MTT and trans-well assay, respectively. Autophagy and underlying molecular mechanisms were investigated using flow cytometry and western blot analysis. Key findings ATD regulated the activity of PI3K/AKT/mTOR and p38MAPK signalling pathways which contributed to autophagy induction. HuCCT-1 cell growth was inhibited by ATD in a time- and dose-dependent manner. ATD inhibited the migration and invasion of HuCCT1 cells in a concentration-dependent manner. It also induced autophagy in HuCCT1 cells in a time- and dose-dependent manner. The SB202190 (autophagy inducer) and 3-MA (autophagy inhibitor) significantly increased and decreased the rate of ATD-induced autophagy, respectively. The 24 h exposure of ATD inhibited the phosphorylation of phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (p38MAPK) and increased Beclin-1 expression and LC3 conversion. It also reduced p-AKT/AKT, p-mTOR/mTOR and p-p38MAPK/p38MAPK. Conclusions ATD inhibits the proliferation and induces CCA cell autophagy via regulating PI3K/AKT/mTOR and p38MAPK signalling pathways.

In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells

“…The role of autophagy as molecular mechanism involved in antitumoral effects is controversial [ 30 , 31 , 32 ]. In this work, we demonstrated for the first time that Rig induces a significant dose-dependent increase in the autophagy process.…”

Atractylodin may induce ferroptosis of human hepatocellular carcinoma cells

“…The clinical practice of treating tumors with traditional Chinese medicine has a long history in China, and the extraction of effective anticancer active ingredients from plants has attracted more and more attention from scholars, playing an important role in alleviating the toxic and side effects of chemoradiotherapy, delaying survival, and improving survival rates (21,22). Studies have reported that atractylodin inhibited bile duct cancer cell migration and induced autophagy through the PI3K/AKT/mTOR and p38MAPK signaling pathways (23), and could significantly improved the survival rate of tumor-bearing rats (24). At present, the effect of atractylodin on HCC has not been reported.…”

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“…DC., AT, and BE against CCA cells mainly involve the induction of cell cycle arrest (at G 1 phase) and apoptosis through activation or suppression of molecular targets/signaling pathways involved in CCA pathogenesis. These include the activation of caspase-3/7 and suppression of HO1 production, activation of STAT1/2 and JAK/STAT signaling cascades, suppression of NFκB, and suppression of cytoprotective enzymes and key growth regulatory transcription factors [38,41,42,62,[98][99][100]. The first-in-human starting dose was estimated from the MRSD (maximum recommended starting dose) from toxicology testing in animals [136], which was 2400 mg for a person weighing 60 kg.…”