Blockade of store-operated calcium entry sensitizes breast cancer cells to cisplatin therapy via modulating inflammatory response
Store-operated calcium entry (SOCE) is an important pathway for calcium signaling that regulates calcium influx across the plasma membrane upon the depletion of calcium stores in the endoplasmic reticulum. SOCE participates in regulating a number of physiological processes including cell proliferati...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | Saudi Pharmaceutical Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016422003085 |
| _version_ | 1811159993359007744 |
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| author | Abdullah S. Alhamed Mohammed Alqinyah Musab A. Alsufayan Ibrahim A. Alhaydan Yasseen A. Alassmrry Hajar O. Alnefaie Mohammad M. Algahtani Adel F. Alghaith Hussain N. Alhamami Abdullah M. Albogami Khalid Alhazzani Alanazi AZ |
| author_facet | Abdullah S. Alhamed Mohammed Alqinyah Musab A. Alsufayan Ibrahim A. Alhaydan Yasseen A. Alassmrry Hajar O. Alnefaie Mohammad M. Algahtani Adel F. Alghaith Hussain N. Alhamami Abdullah M. Albogami Khalid Alhazzani Alanazi AZ |
| author_sort | Abdullah S. Alhamed |
| collection | DOAJ |
| description | Store-operated calcium entry (SOCE) is an important pathway for calcium signaling that regulates calcium influx across the plasma membrane upon the depletion of calcium stores in the endoplasmic reticulum. SOCE participates in regulating a number of physiological processes including cell proliferation and migration while SOCE dysregulation has been linked with pathophysiological conditions such as inflammation and cancer. The crosslink between cancer and inflammation has been well-established where abundant evidence demonstrate that inflammation plays a role in cancer pathophysiology and the response of cancer cells to chemotherapeutic agents including cisplatin. Indeed, the efficacy of cisplatin against cancer cells is reduced by inflammation. Interestingly, it was shown that SOCE enhances inflammatory signaling in immune cells. Therefore, the main objectives of this study are to examine the impact of SOCE inhibition on the cisplatin sensitivity of breast cancer cells and to explore its related mechanism in modulating the inflammatory response in breast cancer cells. Our findings showed that SOCE inhibitor (BTP2) enhanced cisplatin cytotoxicity against resistant breast cancer cells via inhibition of cell proliferation and migration as well as induction of apoptosis. We also found an upregulation in the gene expression of two major components of SOCE, STIM1 and ORAI1, in cisplatin-resistant breast cancer cells compared to cisplatin-sensitive breast cancer cells. In addition, cisplatin treatment increased the gene expression of STIM1 and ORAI1 in cisplatin-resistant breast cancer cells. Finally, this study also demonstrated that cisplatin therapy caused an increase in the gene expression of inflammatory mediators COX2, IL-8, and TNF-α as well as COX2 protein and upon SOCE inhibition using BTP2, the effect of cisplatin on the inflammatory mediators was reversed. Altogether, this study has proven the pivotal role of SOCE in cisplatin resistance of breast cancer cells and showed the importance of targeting this pathway in improving breast cancer therapy. |
| first_indexed | 2024-04-10T05:50:10Z |
| format | Article |
| id | doaj.art-e0164ae4c5194d928d0127fd9b5eff20 |
| institution | Directory Open Access Journal |
| issn | 1319-0164 |
| language | English |
| last_indexed | 2024-04-10T05:50:10Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj.art-e0164ae4c5194d928d0127fd9b5eff202023-03-05T04:23:22ZengElsevierSaudi Pharmaceutical Journal1319-01642023-02-01312245254Blockade of store-operated calcium entry sensitizes breast cancer cells to cisplatin therapy via modulating inflammatory responseAbdullah S. Alhamed0Mohammed Alqinyah1Musab A. Alsufayan2Ibrahim A. Alhaydan3Yasseen A. Alassmrry4Hajar O. Alnefaie5Mohammad M. Algahtani6Adel F. Alghaith7Hussain N. Alhamami8Abdullah M. Albogami9Khalid Alhazzani10Alanazi AZ11Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; Corresponding author.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of pharmaceutics, College of pharmacy, king Saud university, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaStore-operated calcium entry (SOCE) is an important pathway for calcium signaling that regulates calcium influx across the plasma membrane upon the depletion of calcium stores in the endoplasmic reticulum. SOCE participates in regulating a number of physiological processes including cell proliferation and migration while SOCE dysregulation has been linked with pathophysiological conditions such as inflammation and cancer. The crosslink between cancer and inflammation has been well-established where abundant evidence demonstrate that inflammation plays a role in cancer pathophysiology and the response of cancer cells to chemotherapeutic agents including cisplatin. Indeed, the efficacy of cisplatin against cancer cells is reduced by inflammation. Interestingly, it was shown that SOCE enhances inflammatory signaling in immune cells. Therefore, the main objectives of this study are to examine the impact of SOCE inhibition on the cisplatin sensitivity of breast cancer cells and to explore its related mechanism in modulating the inflammatory response in breast cancer cells. Our findings showed that SOCE inhibitor (BTP2) enhanced cisplatin cytotoxicity against resistant breast cancer cells via inhibition of cell proliferation and migration as well as induction of apoptosis. We also found an upregulation in the gene expression of two major components of SOCE, STIM1 and ORAI1, in cisplatin-resistant breast cancer cells compared to cisplatin-sensitive breast cancer cells. In addition, cisplatin treatment increased the gene expression of STIM1 and ORAI1 in cisplatin-resistant breast cancer cells. Finally, this study also demonstrated that cisplatin therapy caused an increase in the gene expression of inflammatory mediators COX2, IL-8, and TNF-α as well as COX2 protein and upon SOCE inhibition using BTP2, the effect of cisplatin on the inflammatory mediators was reversed. Altogether, this study has proven the pivotal role of SOCE in cisplatin resistance of breast cancer cells and showed the importance of targeting this pathway in improving breast cancer therapy.http://www.sciencedirect.com/science/article/pii/S1319016422003085Breast CancerCisplatinSOCEAnd inflammation |
| spellingShingle | Abdullah S. Alhamed Mohammed Alqinyah Musab A. Alsufayan Ibrahim A. Alhaydan Yasseen A. Alassmrry Hajar O. Alnefaie Mohammad M. Algahtani Adel F. Alghaith Hussain N. Alhamami Abdullah M. Albogami Khalid Alhazzani Alanazi AZ Blockade of store-operated calcium entry sensitizes breast cancer cells to cisplatin therapy via modulating inflammatory response Saudi Pharmaceutical Journal Breast Cancer Cisplatin SOCE And inflammation |
| title | Blockade of store-operated calcium entry sensitizes breast cancer cells to cisplatin therapy via modulating inflammatory response |
| title_full | Blockade of store-operated calcium entry sensitizes breast cancer cells to cisplatin therapy via modulating inflammatory response |
| title_fullStr | Blockade of store-operated calcium entry sensitizes breast cancer cells to cisplatin therapy via modulating inflammatory response |
| title_full_unstemmed | Blockade of store-operated calcium entry sensitizes breast cancer cells to cisplatin therapy via modulating inflammatory response |
| title_short | Blockade of store-operated calcium entry sensitizes breast cancer cells to cisplatin therapy via modulating inflammatory response |
| title_sort | blockade of store operated calcium entry sensitizes breast cancer cells to cisplatin therapy via modulating inflammatory response |
| topic | Breast Cancer Cisplatin SOCE And inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S1319016422003085 |
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