Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells

Abstract

The use of dietary bioactive compounds in chemoprevention can potentially reverse, suppress, or even prevent cancer progression. However, the effects of licochalcone A (LicA) on apoptosis and autophagy in cervical cancer cells have not yet been clearly elucidated. In this study, LicA treatment was found to significantly induce the apoptotic and autophagic capacities of cervical cancer cells in vitro and in vivo. MTT assay results showed dose- and time-dependent cytotoxicity in four cervical cancer cell lines treated with LicA. We found that LicA induced mitochondria-dependent apoptosis in SiHa cells, with decreasing Bcl-2 expression. LicA also induced autophagy effects were examined by identifying accumulation of Atg5, Atg7, Atg12 and microtubule-associated protein 1 light chain 3 (LC3)-II. Treatment with autophagy-specific inhibitors (3-methyladenine and bafilomycin A1) enhanced LicA-induced apoptosis. In addition, we suggested the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of mTOR pathway by LicA. Furthermore, the inhibition of PI3K/Akt by LY294002/si-Akt or of mTOR by rapamycin augmented LicA-induced apoptosis and autophagy. Finally, the in vivo mice bearing a SiHa xenograft, LicA dosed at 10 or 20 mg/kg significantly inhibited tumor growth. Our findings demonstrate the chemotherapeutic potential of LicA for treatment of human cervical cancer.

Amarogentin Induces Apoptosis of Liver Cancer Cells via Upregulation of p53 and Downregulation of Human Telomerase Reverse Transcriptase in Mice

“…18,19 Thus, p53 protects against tumor development via the Akt, NF-kb, and hTERT pathways. [20][21][22] In addition, a few studies have reported that p38 is regulated by p53 to induce cancer cell apoptosis, 23,24 and our results have shown that the expression of p38 is not affected by amarogentin in liver cancer cells. In our study, amarogentin also suppressed the expression of Akt, NF-kb, and hTERT.…”

Licochalcone A inhibits PI3K/Akt/mTOR signaling pathway activation and promotes autophagy in breast cancer cells

“…In the present study, Licochalcone A suppressed the PI3K/Akt/mTOR signaling pathway in MCF-7 cells. Tsai et al (18) demonstrated that Licochalcone A induces autophagy through the inhibition of the PI3K/Akt/mTOR signaling pathway in human cervical cancer cells (18). In addition, Hao et al (19) suggested that Licochalcone A induces the apoptosis of BGC-823 human gastric cancer cells via the PI3K/AKT signaling pathway.…”

“…Data from the present study demonstrated that Licochalcone A increases the expression of LC3-II, inhibits Bcl-2 expression and increases caspase-3 activity in MCF-7 cells. Tsai et al (18) demonstrated that Licochalcone A induces autophagy through LC3-II and the inactivation of the PI3K/Akt/mTOR signaling pathway in human cervical cancer cells. The results from the present study revealed that Licochalcone A could induce apoptosis in MCF-7 cells via the caspase-dependent Bcl-2 apoptosis signaling pathway.…”

Protodioscin Induces Apoptosis Through ROS-Mediated Endoplasmic Reticulum Stress via the JNK/p38 Activation Pathways in Human Cervical Cancer Cells

“…The mitochondrial membrane potential was measured by flow cytometry using JC-1 reagent [20]. Briefly, PD-treated cells were incubated with 30 µM JC-1 reagent for 20 min at 37 °C in the dark.…”