Pioglitazone enhances cisplatin’s impact on triple-negative breast cancer: Role of PPARγ in cell apoptosis
Peroxisome proliferator-activated receptor-gamma (PPARγ) has been recently shown to play a role in many cancers. The breast tissue of triple-negative breast cancer (TNBC) patients were found to have a significantly lower expression of PPARγ than the other subtypes. Furthermore, PPARγ activation was...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-05-01
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| Series: | Saudi Pharmaceutical Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016424001099 |
| _version_ | 1827274351495348224 |
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| author | Qamraa Hamad Alqahtani Layla Abdullah Alkharashi Hanaa Alajami Ishraq Alkharashi Layan Alkharashi Shoug Nasser Alhinti |
| author_facet | Qamraa Hamad Alqahtani Layla Abdullah Alkharashi Hanaa Alajami Ishraq Alkharashi Layan Alkharashi Shoug Nasser Alhinti |
| author_sort | Qamraa Hamad Alqahtani |
| collection | DOAJ |
| description | Peroxisome proliferator-activated receptor-gamma (PPARγ) has been recently shown to play a role in many cancers. The breast tissue of triple-negative breast cancer (TNBC) patients were found to have a significantly lower expression of PPARγ than the other subtypes. Furthermore, PPARγ activation was found to exert anti-tumor effects by inhibiting cell proliferation, differentiation, cell growth, cell cycle, and inducing apoptosis. To start with, we performed a bioinformatic analysis of data from OncoDB, which showed a lower expression pattern of PPARγ in different cancer types. In addition, high expression of PPARγ was associated with better breast cancer patient survival. Therefore, we tested the impact of pioglitazone, a PPARγ ligand, on the cytotoxic activity of cisplatin in the TNBC cell line. MDA-MB-231 cells were treated with either cisplatin (40 μM) with or without pioglitazone (30 or 60 μM) for 72 h. The MTT results showed a significant dose-dependent decrease in cell viability as a result of using cisplatin and pioglitazone combination compared with cisplatin alone. In addition, the protein expression of Bcl-2, a known antiapoptotic marker, decreased in the cells treated with cisplatin and pioglitazone combination at doses of 40 and 30 μM, respectively. On the other hand, cleaved- poly-ADP ribose polymerase (PARP) and -caspase-9, which are known as pro-apoptotic markers, were upregulated in the combination group compared with the solo treatments. Taken together, the addition of pioglitazone to cisplatin further reduced the viability of MDA-MB-231 cells and enhanced apoptosis compared with chemotherapy alone. |
| first_indexed | 2024-04-24T13:11:38Z |
| format | Article |
| id | doaj.art-55fb9430f76241f1956ebff2d6ba8cf9 |
| institution | Directory Open Access Journal |
| issn | 1319-0164 |
| language | English |
| last_indexed | 2025-03-22T06:23:38Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj.art-55fb9430f76241f1956ebff2d6ba8cf92024-04-26T04:58:50ZengElsevierSaudi Pharmaceutical Journal1319-01642024-05-01325102059Pioglitazone enhances cisplatin’s impact on triple-negative breast cancer: Role of PPARγ in cell apoptosisQamraa Hamad Alqahtani0Layla Abdullah Alkharashi1Hanaa Alajami2Ishraq Alkharashi3Layan Alkharashi4Shoug Nasser Alhinti5Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia; Corresponding author at: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, PO box: Riyadh 11495, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi ArabiaPharmD Student, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaPharmD Student, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaPharmD Student, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaPeroxisome proliferator-activated receptor-gamma (PPARγ) has been recently shown to play a role in many cancers. The breast tissue of triple-negative breast cancer (TNBC) patients were found to have a significantly lower expression of PPARγ than the other subtypes. Furthermore, PPARγ activation was found to exert anti-tumor effects by inhibiting cell proliferation, differentiation, cell growth, cell cycle, and inducing apoptosis. To start with, we performed a bioinformatic analysis of data from OncoDB, which showed a lower expression pattern of PPARγ in different cancer types. In addition, high expression of PPARγ was associated with better breast cancer patient survival. Therefore, we tested the impact of pioglitazone, a PPARγ ligand, on the cytotoxic activity of cisplatin in the TNBC cell line. MDA-MB-231 cells were treated with either cisplatin (40 μM) with or without pioglitazone (30 or 60 μM) for 72 h. The MTT results showed a significant dose-dependent decrease in cell viability as a result of using cisplatin and pioglitazone combination compared with cisplatin alone. In addition, the protein expression of Bcl-2, a known antiapoptotic marker, decreased in the cells treated with cisplatin and pioglitazone combination at doses of 40 and 30 μM, respectively. On the other hand, cleaved- poly-ADP ribose polymerase (PARP) and -caspase-9, which are known as pro-apoptotic markers, were upregulated in the combination group compared with the solo treatments. Taken together, the addition of pioglitazone to cisplatin further reduced the viability of MDA-MB-231 cells and enhanced apoptosis compared with chemotherapy alone.http://www.sciencedirect.com/science/article/pii/S1319016424001099PioglitazoneCisplatinTriple-negative breast cancerPPARγApoptosis |
| spellingShingle | Qamraa Hamad Alqahtani Layla Abdullah Alkharashi Hanaa Alajami Ishraq Alkharashi Layan Alkharashi Shoug Nasser Alhinti Pioglitazone enhances cisplatin’s impact on triple-negative breast cancer: Role of PPARγ in cell apoptosis Saudi Pharmaceutical Journal Pioglitazone Cisplatin Triple-negative breast cancer PPARγ Apoptosis |
| title | Pioglitazone enhances cisplatin’s impact on triple-negative breast cancer: Role of PPARγ in cell apoptosis |
| title_full | Pioglitazone enhances cisplatin’s impact on triple-negative breast cancer: Role of PPARγ in cell apoptosis |
| title_fullStr | Pioglitazone enhances cisplatin’s impact on triple-negative breast cancer: Role of PPARγ in cell apoptosis |
| title_full_unstemmed | Pioglitazone enhances cisplatin’s impact on triple-negative breast cancer: Role of PPARγ in cell apoptosis |
| title_short | Pioglitazone enhances cisplatin’s impact on triple-negative breast cancer: Role of PPARγ in cell apoptosis |
| title_sort | pioglitazone enhances cisplatin s impact on triple negative breast cancer role of pparγ in cell apoptosis |
| topic | Pioglitazone Cisplatin Triple-negative breast cancer PPARγ Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S1319016424001099 |
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