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.

• Authors: Jen-Pi Tsai, Chien-Hsing Lee, Tsung-Ho Ying, Chu-Liang Lin, Chia-Liang Lin, Jung-Tsung Hsueh, Yi-Hsien Hsieh
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 30 Pg. 28851-66 (Oct 06 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26311737 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chalcones
• Macrolides
• Phosphoinositide-3 Kinase Inhibitors
• Protein Kinase Inhibitors
• 3-methyladenine
• bafilomycin A1
• MTOR protein, human
• Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• Adenine
• licochalcone A

Topics

• Adenine (analogs & derivatives, pharmacology)
• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Cell Proliferation (drug effects)
• Chalcones (pharmacology)
• Dose-Response Relationship, Drug
• Female
• HeLa Cells
• Humans
• Macrolides (pharmacology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Phosphatidylinositol 3-Kinase (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Phosphorylation
• Protein Kinase Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (antagonists & inhibitors, metabolism)
• Time Factors
• Transfection
• Tumor Burden (drug effects)
• Uterine Cervical Neoplasms (drug therapy, enzymology, genetics, pathology)
• Xenograft Model Antitumor Assays