Cargando…

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

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 f...

Descripción completa

Detalles Bibliográficos
Autores principales: Tsai, Jen-Pi, Lee, Chien-Hsing, Ying, Tsung-Ho, Lin, Chu-Liang, Lin, Chia-Liang, Hsueh, Jung-Tsung, Hsieh, Yi-Hsien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745696/
https://www.ncbi.nlm.nih.gov/pubmed/26311737
_version_ 1782414697623977984
author Tsai, Jen-Pi
Lee, Chien-Hsing
Ying, Tsung-Ho
Lin, Chu-Liang
Lin, Chia-Liang
Hsueh, Jung-Tsung
Hsieh, Yi-Hsien
author_facet Tsai, Jen-Pi
Lee, Chien-Hsing
Ying, Tsung-Ho
Lin, Chu-Liang
Lin, Chia-Liang
Hsueh, Jung-Tsung
Hsieh, Yi-Hsien
author_sort Tsai, Jen-Pi
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4745696
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-47456962016-02-23 Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells Tsai, Jen-Pi Lee, Chien-Hsing Ying, Tsung-Ho Lin, Chu-Liang Lin, Chia-Liang Hsueh, Jung-Tsung Hsieh, Yi-Hsien Oncotarget Research Paper 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. Impact Journals LLC 2015-07-31 /pmc/articles/PMC4745696/ /pubmed/26311737 Text en Copyright: © 2015 Tsai et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Tsai, Jen-Pi
Lee, Chien-Hsing
Ying, Tsung-Ho
Lin, Chu-Liang
Lin, Chia-Liang
Hsueh, Jung-Tsung
Hsieh, Yi-Hsien
Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells
title Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells
title_full Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells
title_fullStr Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells
title_full_unstemmed Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells
title_short Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells
title_sort licochalcone a induces autophagy through pi3k/akt/mtor inactivation and autophagy suppression enhances licochalcone a-induced apoptosis of human cervical cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745696/
https://www.ncbi.nlm.nih.gov/pubmed/26311737
work_keys_str_mv AT tsaijenpi licochalconeainducesautophagythroughpi3kaktmtorinactivationandautophagysuppressionenhanceslicochalconeainducedapoptosisofhumancervicalcancercells
AT leechienhsing licochalconeainducesautophagythroughpi3kaktmtorinactivationandautophagysuppressionenhanceslicochalconeainducedapoptosisofhumancervicalcancercells
AT yingtsungho licochalconeainducesautophagythroughpi3kaktmtorinactivationandautophagysuppressionenhanceslicochalconeainducedapoptosisofhumancervicalcancercells
AT linchuliang licochalconeainducesautophagythroughpi3kaktmtorinactivationandautophagysuppressionenhanceslicochalconeainducedapoptosisofhumancervicalcancercells
AT linchialiang licochalconeainducesautophagythroughpi3kaktmtorinactivationandautophagysuppressionenhanceslicochalconeainducedapoptosisofhumancervicalcancercells
AT hsuehjungtsung licochalconeainducesautophagythroughpi3kaktmtorinactivationandautophagysuppressionenhanceslicochalconeainducedapoptosisofhumancervicalcancercells
AT hsiehyihsien licochalconeainducesautophagythroughpi3kaktmtorinactivationandautophagysuppressionenhanceslicochalconeainducedapoptosisofhumancervicalcancercells