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Gossypol Induces Apoptosis of Human Pancreatic Cancer Cells via CHOP/Endoplasmic Reticulum Stress Signaling Pathway

Gossypol, a natural phenolic aldehyde present in cotton plants, was originally used as a means of contraception, but is currently being studied for its anti-proliferative and anti-metastatic effects on various cancers. However, the intracellular mechanism of action regarding the effects of gossypol...

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Autores principales: Lee, Soon, Hong, Eunmi, Jo, Eunbi, Kim, Z-Hun, Yim, Kyung June, Woo, Sung Hwan, Choi, Yong-Soo, Jang, Hyun-Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society for Microbiology and Biotechnology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9628887/
https://www.ncbi.nlm.nih.gov/pubmed/35283426
http://dx.doi.org/10.4014/jmb.2110.10019
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author Lee, Soon
Hong, Eunmi
Jo, Eunbi
Kim, Z-Hun
Yim, Kyung June
Woo, Sung Hwan
Choi, Yong-Soo
Jang, Hyun-Jin
author_facet Lee, Soon
Hong, Eunmi
Jo, Eunbi
Kim, Z-Hun
Yim, Kyung June
Woo, Sung Hwan
Choi, Yong-Soo
Jang, Hyun-Jin
author_sort Lee, Soon
collection PubMed
description Gossypol, a natural phenolic aldehyde present in cotton plants, was originally used as a means of contraception, but is currently being studied for its anti-proliferative and anti-metastatic effects on various cancers. However, the intracellular mechanism of action regarding the effects of gossypol on pancreatic cancer cells remains unclear. Here, we investigated the anti-cancer effects of gossypol on human pancreatic cancer cells (BxPC-3 and MIA PaCa-2). Cell counting kit-8 assays, annexin V/propidium iodide staining assays, and transmission electron microscopy showed that gossypol induced apoptotic cell death and apoptotic body formation in both cell lines. RNA sequencing analysis also showed that gossypol increased the mRNA levels of CCAAT/enhancer-binding protein homologous protein (CHOP) and activating transcription factor 3 (ATF3) in pancreatic cancer cell lines. In addition, gossypol facilitated the cleavage of caspase-3 via protein kinase RNA-like ER kinase (PERK), CHOP, and Bax/Bcl-2 upregulation in both cells, whereas the upregulation of ATF was limited to BxPC-3 cells. Finally, a three-dimensional culture experiment confirmed the successful suppression of cancer cell spheroids via gossypol treatment. Taken together, our data suggest that gossypol may trigger apoptosis in pancreatic cancer cells via the PERK-CHOP signaling pathway. These findings propose a promising therapeutic approach to pancreatic cancer treatment using gossypol.
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spelling pubmed-96288872022-12-13 Gossypol Induces Apoptosis of Human Pancreatic Cancer Cells via CHOP/Endoplasmic Reticulum Stress Signaling Pathway Lee, Soon Hong, Eunmi Jo, Eunbi Kim, Z-Hun Yim, Kyung June Woo, Sung Hwan Choi, Yong-Soo Jang, Hyun-Jin J Microbiol Biotechnol Research article Gossypol, a natural phenolic aldehyde present in cotton plants, was originally used as a means of contraception, but is currently being studied for its anti-proliferative and anti-metastatic effects on various cancers. However, the intracellular mechanism of action regarding the effects of gossypol on pancreatic cancer cells remains unclear. Here, we investigated the anti-cancer effects of gossypol on human pancreatic cancer cells (BxPC-3 and MIA PaCa-2). Cell counting kit-8 assays, annexin V/propidium iodide staining assays, and transmission electron microscopy showed that gossypol induced apoptotic cell death and apoptotic body formation in both cell lines. RNA sequencing analysis also showed that gossypol increased the mRNA levels of CCAAT/enhancer-binding protein homologous protein (CHOP) and activating transcription factor 3 (ATF3) in pancreatic cancer cell lines. In addition, gossypol facilitated the cleavage of caspase-3 via protein kinase RNA-like ER kinase (PERK), CHOP, and Bax/Bcl-2 upregulation in both cells, whereas the upregulation of ATF was limited to BxPC-3 cells. Finally, a three-dimensional culture experiment confirmed the successful suppression of cancer cell spheroids via gossypol treatment. Taken together, our data suggest that gossypol may trigger apoptosis in pancreatic cancer cells via the PERK-CHOP signaling pathway. These findings propose a promising therapeutic approach to pancreatic cancer treatment using gossypol. The Korean Society for Microbiology and Biotechnology 2022-05-28 2022-02-23 /pmc/articles/PMC9628887/ /pubmed/35283426 http://dx.doi.org/10.4014/jmb.2110.10019 Text en Copyright © 2022 by the authors. Licensee KMB. https://creativecommons.org/licenses/by/4.0/This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research article
Lee, Soon
Hong, Eunmi
Jo, Eunbi
Kim, Z-Hun
Yim, Kyung June
Woo, Sung Hwan
Choi, Yong-Soo
Jang, Hyun-Jin
Gossypol Induces Apoptosis of Human Pancreatic Cancer Cells via CHOP/Endoplasmic Reticulum Stress Signaling Pathway
title Gossypol Induces Apoptosis of Human Pancreatic Cancer Cells via CHOP/Endoplasmic Reticulum Stress Signaling Pathway
title_full Gossypol Induces Apoptosis of Human Pancreatic Cancer Cells via CHOP/Endoplasmic Reticulum Stress Signaling Pathway
title_fullStr Gossypol Induces Apoptosis of Human Pancreatic Cancer Cells via CHOP/Endoplasmic Reticulum Stress Signaling Pathway
title_full_unstemmed Gossypol Induces Apoptosis of Human Pancreatic Cancer Cells via CHOP/Endoplasmic Reticulum Stress Signaling Pathway
title_short Gossypol Induces Apoptosis of Human Pancreatic Cancer Cells via CHOP/Endoplasmic Reticulum Stress Signaling Pathway
title_sort gossypol induces apoptosis of human pancreatic cancer cells via chop/endoplasmic reticulum stress signaling pathway
topic Research article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9628887/
https://www.ncbi.nlm.nih.gov/pubmed/35283426
http://dx.doi.org/10.4014/jmb.2110.10019
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