Response of Breast Cancer Cells to PARP Inhibitors Is Independent of BRCA Status
Poly (ADP-ribose) polymerase inhibitors (PARPi) have proven to be beneficial to patients with metastatic breast cancer with BRCA1/2 (BReast CAncer type 1 and type 2 genes) mutations. However, certain PARPi in pre-clinical studies have been shown to inhibit cell growth and promote the death of breast...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/9/4/940 |
| _version_ | 1797571949057015808 |
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| author | Man Yee Keung Yanyuan Wu Francesca Badar Jaydutt V. Vadgama |
| author_facet | Man Yee Keung Yanyuan Wu Francesca Badar Jaydutt V. Vadgama |
| author_sort | Man Yee Keung |
| collection | DOAJ |
| description | Poly (ADP-ribose) polymerase inhibitors (PARPi) have proven to be beneficial to patients with metastatic breast cancer with BRCA1/2 (BReast CAncer type 1 and type 2 genes) mutations. However, certain PARPi in pre-clinical studies have been shown to inhibit cell growth and promote the death of breast cancer cells lacking mutations in BRCA1/2. Here, we examined the inhibitory potency of 13 different PARPi in 12 breast cancer cell lines with and without BRCA-mutations using cell viability assays. The results showed that 5 of the 8 triple-negative breast cancer (TNBC) cell lines were susceptible to PARPi regardless of the BRCA-status. The estrogen receptor (ER) negative/ human epidermal growth factor receptor 2 (HER2) positive (ER-/HER2+) cells, SKBR3 and JIMT1, showed high sensitivity to Talazoparib. Especially JIMT1, which is known to be resistant to trastuzumab, was responsive to Talazoparib at 0.002 µM. Niraparib, Olaparib, and Rucaparib also demonstrated effective inhibitory potency in both advanced TNBC and ER-/HER2+ cells with and without BRCA-mutations. In contrast, a BRCA-mutant TNBC line, HCC1937, was less sensitive to Talazoparib, Niraparib, Rucaparib, and not responsive to Olaparib. Other PARPi such as UPF1069, NU1025, AZD2461, and PJ34HCl also showed potent inhibitory activity in specific breast cancer cells. Our data suggest that the benefit of PARPi therapy in breast cancer is beyond the BRCA-mutations, and equally effective on metastatic TNBC and ER-/HER2+ breast cancers. |
| first_indexed | 2024-03-10T20:48:50Z |
| format | Article |
| id | doaj.art-68428062eb3542058e757eb5f8086351 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T20:48:50Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-68428062eb3542058e757eb5f80863512023-11-19T20:07:22ZengMDPI AGJournal of Clinical Medicine2077-03832020-03-019494010.3390/jcm9040940Response of Breast Cancer Cells to PARP Inhibitors Is Independent of BRCA StatusMan Yee Keung0Yanyuan Wu1Francesca Badar2Jaydutt V. Vadgama3Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USADivision of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USADivision of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USADivision of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USAPoly (ADP-ribose) polymerase inhibitors (PARPi) have proven to be beneficial to patients with metastatic breast cancer with BRCA1/2 (BReast CAncer type 1 and type 2 genes) mutations. However, certain PARPi in pre-clinical studies have been shown to inhibit cell growth and promote the death of breast cancer cells lacking mutations in BRCA1/2. Here, we examined the inhibitory potency of 13 different PARPi in 12 breast cancer cell lines with and without BRCA-mutations using cell viability assays. The results showed that 5 of the 8 triple-negative breast cancer (TNBC) cell lines were susceptible to PARPi regardless of the BRCA-status. The estrogen receptor (ER) negative/ human epidermal growth factor receptor 2 (HER2) positive (ER-/HER2+) cells, SKBR3 and JIMT1, showed high sensitivity to Talazoparib. Especially JIMT1, which is known to be resistant to trastuzumab, was responsive to Talazoparib at 0.002 µM. Niraparib, Olaparib, and Rucaparib also demonstrated effective inhibitory potency in both advanced TNBC and ER-/HER2+ cells with and without BRCA-mutations. In contrast, a BRCA-mutant TNBC line, HCC1937, was less sensitive to Talazoparib, Niraparib, Rucaparib, and not responsive to Olaparib. Other PARPi such as UPF1069, NU1025, AZD2461, and PJ34HCl also showed potent inhibitory activity in specific breast cancer cells. Our data suggest that the benefit of PARPi therapy in breast cancer is beyond the BRCA-mutations, and equally effective on metastatic TNBC and ER-/HER2+ breast cancers.https://www.mdpi.com/2077-0383/9/4/940PARP inhibitorsTriple-negative breast cancerBRCA1/2 mutationsHER2-positive breast cancer |
| spellingShingle | Man Yee Keung Yanyuan Wu Francesca Badar Jaydutt V. Vadgama Response of Breast Cancer Cells to PARP Inhibitors Is Independent of BRCA Status Journal of Clinical Medicine PARP inhibitors Triple-negative breast cancer BRCA1/2 mutations HER2-positive breast cancer |
| title | Response of Breast Cancer Cells to PARP Inhibitors Is Independent of BRCA Status |
| title_full | Response of Breast Cancer Cells to PARP Inhibitors Is Independent of BRCA Status |
| title_fullStr | Response of Breast Cancer Cells to PARP Inhibitors Is Independent of BRCA Status |
| title_full_unstemmed | Response of Breast Cancer Cells to PARP Inhibitors Is Independent of BRCA Status |
| title_short | Response of Breast Cancer Cells to PARP Inhibitors Is Independent of BRCA Status |
| title_sort | response of breast cancer cells to parp inhibitors is independent of brca status |
| topic | PARP inhibitors Triple-negative breast cancer BRCA1/2 mutations HER2-positive breast cancer |
| url | https://www.mdpi.com/2077-0383/9/4/940 |
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