Chloroquine Potentiates the Anticancer Effect of Pterostilbene on Pancreatic Cancer by Inhibiting Autophagy and Downregulating the RAGE/STAT3 Pathway

The treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, because pro-survival signaling pathways—such as the receptor for advanced glycation end products (RAGE)/signal transducer and activator of transcription 3 (STAT3) pathway—are overexpressed in PDAC cells. Moreover, PDA...

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Autores principales:	Rong-Jane Chen, Yi-Jhen Lyu, Yu-Ying Chen, Yen-Chien Lee, Min-Hsiung Pan, Yuan-Soon Ho, Ying-Jan Wang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	pterostilbene pancreatic ductal adenocarcinoma chloroquine RAGE/STAT3 autophagy apoptosis Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/1ecc510839574922bf82ba1ac4f3fdfc
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spelling	oai:doaj.org-article:1ecc510839574922bf82ba1ac4f3fdfc2021-11-11T18:40:28ZChloroquine Potentiates the Anticancer Effect of Pterostilbene on Pancreatic Cancer by Inhibiting Autophagy and Downregulating the RAGE/STAT3 Pathway10.3390/molecules262167411420-3049https://doaj.org/article/1ecc510839574922bf82ba1ac4f3fdfc2021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6741https://doaj.org/toc/1420-3049The treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, because pro-survival signaling pathways—such as the receptor for advanced glycation end products (RAGE)/signal transducer and activator of transcription 3 (STAT3) pathway—are overexpressed in PDAC cells. Moreover, PDAC cells are highly resistant to chemotherapeutic agents because of autophagy induction. Therefore, autophagy and its modulated signaling pathways are attractive targets for developing novel therapeutic strategies for PDAC. Pterostilbene is a stilbenoid chemically related to resveratrol, and has potential for the treatment of cancers. Accordingly, we investigated whether the autophagy inhibitor chloroquine could potentiate the anticancer effect of pterostilbene in the PDAC cell lines MIA PaCa-2 and BxPC-3, as well as in an orthotopic animal model. The results indicated that pterostilbene combined with chloroquine significantly inhibited autophagy, decreased cell viability, and sensitized the cells to pterostilbene-induced apoptosis via downregulation of the RAGE/STAT3 and protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways in PDAC cells. The results of the orthotopic animal model showed that pterostilbene combined with chloroquine significantly inhibited pancreatic cancer growth, delayed tumor quadrupling times, and inhibited autophagy and STAT3 in pancreatic tumors. In summary, the present study suggested the novel therapeutic strategy of pterostilbene combined with chloroquine against the growth of pancreatic ductal adenocarcinoma by inhibiting autophagy and downregulating the RAGE/STAT3 signaling pathways.Rong-Jane ChenYi-Jhen LyuYu-Ying ChenYen-Chien LeeMin-Hsiung PanYuan-Soon HoYing-Jan WangMDPI AGarticlepterostilbenepancreatic ductal adenocarcinomachloroquineRAGE/STAT3autophagyapoptosisOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6741, p 6741 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pterostilbene pancreatic ductal adenocarcinoma chloroquine RAGE/STAT3 autophagy apoptosis Organic chemistry QD241-441
spellingShingle	pterostilbene pancreatic ductal adenocarcinoma chloroquine RAGE/STAT3 autophagy apoptosis Organic chemistry QD241-441 Rong-Jane Chen Yi-Jhen Lyu Yu-Ying Chen Yen-Chien Lee Min-Hsiung Pan Yuan-Soon Ho Ying-Jan Wang Chloroquine Potentiates the Anticancer Effect of Pterostilbene on Pancreatic Cancer by Inhibiting Autophagy and Downregulating the RAGE/STAT3 Pathway
description	The treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, because pro-survival signaling pathways—such as the receptor for advanced glycation end products (RAGE)/signal transducer and activator of transcription 3 (STAT3) pathway—are overexpressed in PDAC cells. Moreover, PDAC cells are highly resistant to chemotherapeutic agents because of autophagy induction. Therefore, autophagy and its modulated signaling pathways are attractive targets for developing novel therapeutic strategies for PDAC. Pterostilbene is a stilbenoid chemically related to resveratrol, and has potential for the treatment of cancers. Accordingly, we investigated whether the autophagy inhibitor chloroquine could potentiate the anticancer effect of pterostilbene in the PDAC cell lines MIA PaCa-2 and BxPC-3, as well as in an orthotopic animal model. The results indicated that pterostilbene combined with chloroquine significantly inhibited autophagy, decreased cell viability, and sensitized the cells to pterostilbene-induced apoptosis via downregulation of the RAGE/STAT3 and protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways in PDAC cells. The results of the orthotopic animal model showed that pterostilbene combined with chloroquine significantly inhibited pancreatic cancer growth, delayed tumor quadrupling times, and inhibited autophagy and STAT3 in pancreatic tumors. In summary, the present study suggested the novel therapeutic strategy of pterostilbene combined with chloroquine against the growth of pancreatic ductal adenocarcinoma by inhibiting autophagy and downregulating the RAGE/STAT3 signaling pathways.
format	article
author	Rong-Jane Chen Yi-Jhen Lyu Yu-Ying Chen Yen-Chien Lee Min-Hsiung Pan Yuan-Soon Ho Ying-Jan Wang
author_facet	Rong-Jane Chen Yi-Jhen Lyu Yu-Ying Chen Yen-Chien Lee Min-Hsiung Pan Yuan-Soon Ho Ying-Jan Wang
author_sort	Rong-Jane Chen
title	Chloroquine Potentiates the Anticancer Effect of Pterostilbene on Pancreatic Cancer by Inhibiting Autophagy and Downregulating the RAGE/STAT3 Pathway
title_short	Chloroquine Potentiates the Anticancer Effect of Pterostilbene on Pancreatic Cancer by Inhibiting Autophagy and Downregulating the RAGE/STAT3 Pathway
title_full	Chloroquine Potentiates the Anticancer Effect of Pterostilbene on Pancreatic Cancer by Inhibiting Autophagy and Downregulating the RAGE/STAT3 Pathway
title_fullStr	Chloroquine Potentiates the Anticancer Effect of Pterostilbene on Pancreatic Cancer by Inhibiting Autophagy and Downregulating the RAGE/STAT3 Pathway
title_full_unstemmed	Chloroquine Potentiates the Anticancer Effect of Pterostilbene on Pancreatic Cancer by Inhibiting Autophagy and Downregulating the RAGE/STAT3 Pathway
title_sort	chloroquine potentiates the anticancer effect of pterostilbene on pancreatic cancer by inhibiting autophagy and downregulating the rage/stat3 pathway
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1ecc510839574922bf82ba1ac4f3fdfc
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Chloroquine Potentiates the Anticancer Effect of Pterostilbene on Pancreatic Cancer by Inhibiting Autophagy and Downregulating the RAGE/STAT3 Pathway

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