Oncotarget

Research Papers:

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

Jen-Pi Tsai, Chien-Hsing Lee, Tsung-Ho Ying, Chu-Liang Lin, Chia-Liang Lin, Jung-Tsung Hsueh and Yi-Hsien Hsieh _

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Oncotarget. 2015; 6:28851-28866. https://doi.org/10.18632/oncotarget.4767

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Abstract

Jen-Pi Tsai1,2,*, Chien-Hsing Lee3,4,*, Tsung-Ho Ying5, Chu-Liang Lin6, Chia-Liang Lin6, Jung-Tsung Hsueh6, Yi-Hsien Hsieh6,7,8

1Department of Nephrology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan

2School of Medicine, Tzu Chi University, Hualien, Taiwan

3Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan, Taiwan

4Division of Pediatric Surgery, Department of Surgery, Children's Hospital of China Medical University, Taichung, Taiwan

5Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan

6Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan

7Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan

8Clinical laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan

*These authors contributed equally to this work

Correspondence to:

Yi-Hsien Hsieh, e-mail: hyhsien@csmu.edu.tw

Keywords: Licochalcone A, apoptosis, autophagy, cervical cancer

Received: May 04, 2015     Accepted: July 20, 2015     Published: July 31, 2015

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.


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