Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells
| Autor: | Chien-Hsing Lee, Chu Liang Lin, Jen Pi Tsai, Yi-Hsien Hsieh, Tsung Ho Ying, Jung Tsung Hsueh, Chia Liang Lin |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
autophagy
Time Factors Licochalcone A cervical cancer ATG5 Mice Nude Uterine Cervical Neoplasms Apoptosis Biology Transfection ATG12 Mice chemistry.chemical_compound Chalcones Antineoplastic Combined Chemotherapy Protocols Animals Humans MTT assay Phosphorylation Protein Kinase Inhibitors Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Phosphoinositide-3 Kinase Inhibitors Mice Inbred BALB C Dose-Response Relationship Drug Adenine TOR Serine-Threonine Kinases Autophagy Xenograft Model Antitumor Assays Tumor Burden Oncology chemistry Cancer research Female Macrolides Phosphatidylinositol 3-Kinase Proto-Oncogene Proteins c-akt Research Paper HeLa Cells Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.4767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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