Cargando…

3,3'-Diindolylmethane induces gastric cancer cells death via STIM1 mediated store-operated calcium entry

3,3'-Diindolylmethane (DIM), a natural phytochemicals isolated from cruciferous vegetables, has been reported to inhibit human gastric cancer cells proliferation and induce cells apoptosis as well as autophagy, but its mechanisms are still unclear. Store-operated calcium entry (SOCE) is a main...

Descripción completa

Detalles Bibliográficos
Autores principales: Ye, Yang, Li, Xue, Wang, Zhihua, Ye, Fen, Xu, Wenrong, Lu, Rongzhu, Shen, Haijun, Miao, Shuhan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040462/
https://www.ncbi.nlm.nih.gov/pubmed/33867841
http://dx.doi.org/10.7150/ijbs.56833
_version_ 1783677791354486784
author Ye, Yang
Li, Xue
Wang, Zhihua
Ye, Fen
Xu, Wenrong
Lu, Rongzhu
Shen, Haijun
Miao, Shuhan
author_facet Ye, Yang
Li, Xue
Wang, Zhihua
Ye, Fen
Xu, Wenrong
Lu, Rongzhu
Shen, Haijun
Miao, Shuhan
author_sort Ye, Yang
collection PubMed
description 3,3'-Diindolylmethane (DIM), a natural phytochemicals isolated from cruciferous vegetables, has been reported to inhibit human gastric cancer cells proliferation and induce cells apoptosis as well as autophagy, but its mechanisms are still unclear. Store-operated calcium entry (SOCE) is a main Ca(2+) influx pathway in various of cancers, which is activated by the depletion of endoplasmic reticulum (ER) Ca(2+) store. Stromal interaction molecular 1 (STIM1) is the necessary component of SOCE. In this study, we focus on to examine the regulatory mechanism of SOCE on DIM-induced death in gastric cancer. After treating the human BGC-823 and SGC-7901 gastric cancer cells with DIM, cellular proliferation was determined by MTT, apoptosis and autophagy were detected by flow cytometry or Hoechst 33342 staining. The expression levels of related proteins were evaluated by Western blotting. Free cytosolilc Ca(2+) level was assessed by fluorescence monitoring under a laser scanning confocal microscope. The data have shown that DIM could significantly inhibit proliferation and induce apoptosis as well as autophagy in two gastric cancer cell lines. After DIM treatment, the STIM1-mediated SOCE was activated by upregulating STIM1 and decreasing ER Ca(2+) level. Knockdown STIM1 with siRNA or pharmacological inhibition of SOCE attenuated DIM induced apoptosis and autophagy by inhibiting p-AMPK mediated ER stress pathway. Our data highlighted that the potential of SOCE as a promising target for treating cancers. Developing effective and selective activators targeting STIM1-mediated SOCE pathway will facilitate better therapeutic sensitivity of phytochemicals acting on SOCE in gastric cancer. Moreover, more research should be performed to validate the efficacy of combination chemotherapy of anti-cancer drugs targeting SOCE for clinical application.
format Online
Article
Text
id pubmed-8040462
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Ivyspring International Publisher
record_format MEDLINE/PubMed
spelling pubmed-80404622021-04-15 3,3'-Diindolylmethane induces gastric cancer cells death via STIM1 mediated store-operated calcium entry Ye, Yang Li, Xue Wang, Zhihua Ye, Fen Xu, Wenrong Lu, Rongzhu Shen, Haijun Miao, Shuhan Int J Biol Sci Research Paper 3,3'-Diindolylmethane (DIM), a natural phytochemicals isolated from cruciferous vegetables, has been reported to inhibit human gastric cancer cells proliferation and induce cells apoptosis as well as autophagy, but its mechanisms are still unclear. Store-operated calcium entry (SOCE) is a main Ca(2+) influx pathway in various of cancers, which is activated by the depletion of endoplasmic reticulum (ER) Ca(2+) store. Stromal interaction molecular 1 (STIM1) is the necessary component of SOCE. In this study, we focus on to examine the regulatory mechanism of SOCE on DIM-induced death in gastric cancer. After treating the human BGC-823 and SGC-7901 gastric cancer cells with DIM, cellular proliferation was determined by MTT, apoptosis and autophagy were detected by flow cytometry or Hoechst 33342 staining. The expression levels of related proteins were evaluated by Western blotting. Free cytosolilc Ca(2+) level was assessed by fluorescence monitoring under a laser scanning confocal microscope. The data have shown that DIM could significantly inhibit proliferation and induce apoptosis as well as autophagy in two gastric cancer cell lines. After DIM treatment, the STIM1-mediated SOCE was activated by upregulating STIM1 and decreasing ER Ca(2+) level. Knockdown STIM1 with siRNA or pharmacological inhibition of SOCE attenuated DIM induced apoptosis and autophagy by inhibiting p-AMPK mediated ER stress pathway. Our data highlighted that the potential of SOCE as a promising target for treating cancers. Developing effective and selective activators targeting STIM1-mediated SOCE pathway will facilitate better therapeutic sensitivity of phytochemicals acting on SOCE in gastric cancer. Moreover, more research should be performed to validate the efficacy of combination chemotherapy of anti-cancer drugs targeting SOCE for clinical application. Ivyspring International Publisher 2021-03-19 /pmc/articles/PMC8040462/ /pubmed/33867841 http://dx.doi.org/10.7150/ijbs.56833 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Ye, Yang
Li, Xue
Wang, Zhihua
Ye, Fen
Xu, Wenrong
Lu, Rongzhu
Shen, Haijun
Miao, Shuhan
3,3'-Diindolylmethane induces gastric cancer cells death via STIM1 mediated store-operated calcium entry
title 3,3'-Diindolylmethane induces gastric cancer cells death via STIM1 mediated store-operated calcium entry
title_full 3,3'-Diindolylmethane induces gastric cancer cells death via STIM1 mediated store-operated calcium entry
title_fullStr 3,3'-Diindolylmethane induces gastric cancer cells death via STIM1 mediated store-operated calcium entry
title_full_unstemmed 3,3'-Diindolylmethane induces gastric cancer cells death via STIM1 mediated store-operated calcium entry
title_short 3,3'-Diindolylmethane induces gastric cancer cells death via STIM1 mediated store-operated calcium entry
title_sort 3,3'-diindolylmethane induces gastric cancer cells death via stim1 mediated store-operated calcium entry
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040462/
https://www.ncbi.nlm.nih.gov/pubmed/33867841
http://dx.doi.org/10.7150/ijbs.56833
work_keys_str_mv AT yeyang 33diindolylmethaneinducesgastriccancercellsdeathviastim1mediatedstoreoperatedcalciumentry
AT lixue 33diindolylmethaneinducesgastriccancercellsdeathviastim1mediatedstoreoperatedcalciumentry
AT wangzhihua 33diindolylmethaneinducesgastriccancercellsdeathviastim1mediatedstoreoperatedcalciumentry
AT yefen 33diindolylmethaneinducesgastriccancercellsdeathviastim1mediatedstoreoperatedcalciumentry
AT xuwenrong 33diindolylmethaneinducesgastriccancercellsdeathviastim1mediatedstoreoperatedcalciumentry
AT lurongzhu 33diindolylmethaneinducesgastriccancercellsdeathviastim1mediatedstoreoperatedcalciumentry
AT shenhaijun 33diindolylmethaneinducesgastriccancercellsdeathviastim1mediatedstoreoperatedcalciumentry
AT miaoshuhan 33diindolylmethaneinducesgastriccancercellsdeathviastim1mediatedstoreoperatedcalciumentry