The Anti-Cancer Effects of Mitochondrial-Targeted Triphenylphosphonium–Resveratrol Conjugate on Breast Cancer Cells
Breast cancer is the most commonly diagnosed cancer in women. Resveratrol, a naturally occurring phytochemical, shows great promise in developing novel anti-cancer therapies. This study hypothesized that the mitochondria-targeted delivery of resveratrol would increase its potency and induce mitochon...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/10/1271 |
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| author | Lingling Jiang Han Yu Chenwei Wang Fujin He Zhongqi Shi Haohong Tu Na Ning Shaofeng Duan Yunqi Zhao |
| author_facet | Lingling Jiang Han Yu Chenwei Wang Fujin He Zhongqi Shi Haohong Tu Na Ning Shaofeng Duan Yunqi Zhao |
| author_sort | Lingling Jiang |
| collection | DOAJ |
| description | Breast cancer is the most commonly diagnosed cancer in women. Resveratrol, a naturally occurring phytochemical, shows great promise in developing novel anti-cancer therapies. This study hypothesized that the mitochondria-targeted delivery of resveratrol would increase its potency and induce mitochondria-mediated apoptosis. The targeted delivery of resveratrol was achieved by conjugating resveratrol to triphenylphosphonium (TPP). The anti-cancer effects of TPP-resveratrol were studied in the murine breast cancer 4T1 and the human breast cancer MDA-MB-231 cell lines. Flow cytometry was used to study apoptosis induction, cell cycle arrest, and mitochondrial membrane potential loss. The morphological changes in the mitochondria in MDA-MB-231 cells after TPP-resveratrol treatments were examined using transmission electron microscopy. Moreover, the changes in MDA-MB-231 cell metabolism after resveratrol and TPP-resveratrol treatments were studied using metabolomic analysis. We demonstrate that TPP-resveratrol significantly improved cytotoxicity in 4T1 cells and MDA-MB-231 cells by inducing apoptosis and mitochondrial membrane potential loss. Swollen and vacuolated mitochondria were observed after the TPP-resveratrol treatment. Meanwhile, TPP-resveratrol treatment down-regulated amino acid and energy metabolism and caused the dysfunction of purine and pyrimidine metabolism. Our results provide evidence supporting the targeted delivery of resveratrol to mitochondria and suggest that TPP-resveratrol may be an effective agent for breast cancer treatment. |
| first_indexed | 2024-03-09T19:36:54Z |
| format | Article |
| id | doaj.art-c5fa31982aaa49a6a7ca207b1003f65e |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T19:36:54Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-c5fa31982aaa49a6a7ca207b1003f65e2023-11-24T01:52:20ZengMDPI AGPharmaceuticals1424-82472022-10-011510127110.3390/ph15101271The Anti-Cancer Effects of Mitochondrial-Targeted Triphenylphosphonium–Resveratrol Conjugate on Breast Cancer CellsLingling Jiang0Han Yu1Chenwei Wang2Fujin He3Zhongqi Shi4Haohong Tu5Na Ning6Shaofeng Duan7Yunqi Zhao8Wenzhou Municipal Key Lab of Applied Biomedical and Biopharmaceutical Informatics, Wenzhou-Kean University, Wenzhou 325060, ChinaWenzhou Municipal Key Lab of Applied Biomedical and Biopharmaceutical Informatics, Wenzhou-Kean University, Wenzhou 325060, ChinaSchool of Pharmacy, Henan University, Kaifeng 475004, ChinaSchool of Pharmacy, Henan University, Kaifeng 475004, ChinaSchool of Pharmacy, Henan University, Kaifeng 475004, ChinaWenzhou Municipal Key Lab of Applied Biomedical and Biopharmaceutical Informatics, Wenzhou-Kean University, Wenzhou 325060, ChinaWenzhou Municipal Key Lab of Applied Biomedical and Biopharmaceutical Informatics, Wenzhou-Kean University, Wenzhou 325060, ChinaSchool of Pharmacy, Henan University, Kaifeng 475004, ChinaWenzhou Municipal Key Lab of Applied Biomedical and Biopharmaceutical Informatics, Wenzhou-Kean University, Wenzhou 325060, ChinaBreast cancer is the most commonly diagnosed cancer in women. Resveratrol, a naturally occurring phytochemical, shows great promise in developing novel anti-cancer therapies. This study hypothesized that the mitochondria-targeted delivery of resveratrol would increase its potency and induce mitochondria-mediated apoptosis. The targeted delivery of resveratrol was achieved by conjugating resveratrol to triphenylphosphonium (TPP). The anti-cancer effects of TPP-resveratrol were studied in the murine breast cancer 4T1 and the human breast cancer MDA-MB-231 cell lines. Flow cytometry was used to study apoptosis induction, cell cycle arrest, and mitochondrial membrane potential loss. The morphological changes in the mitochondria in MDA-MB-231 cells after TPP-resveratrol treatments were examined using transmission electron microscopy. Moreover, the changes in MDA-MB-231 cell metabolism after resveratrol and TPP-resveratrol treatments were studied using metabolomic analysis. We demonstrate that TPP-resveratrol significantly improved cytotoxicity in 4T1 cells and MDA-MB-231 cells by inducing apoptosis and mitochondrial membrane potential loss. Swollen and vacuolated mitochondria were observed after the TPP-resveratrol treatment. Meanwhile, TPP-resveratrol treatment down-regulated amino acid and energy metabolism and caused the dysfunction of purine and pyrimidine metabolism. Our results provide evidence supporting the targeted delivery of resveratrol to mitochondria and suggest that TPP-resveratrol may be an effective agent for breast cancer treatment.https://www.mdpi.com/1424-8247/15/10/1271mitochondrial targetingtriphenylphosphoniumresveratrolbreast cancermetabolomics |
| spellingShingle | Lingling Jiang Han Yu Chenwei Wang Fujin He Zhongqi Shi Haohong Tu Na Ning Shaofeng Duan Yunqi Zhao The Anti-Cancer Effects of Mitochondrial-Targeted Triphenylphosphonium–Resveratrol Conjugate on Breast Cancer Cells Pharmaceuticals mitochondrial targeting triphenylphosphonium resveratrol breast cancer metabolomics |
| title | The Anti-Cancer Effects of Mitochondrial-Targeted Triphenylphosphonium–Resveratrol Conjugate on Breast Cancer Cells |
| title_full | The Anti-Cancer Effects of Mitochondrial-Targeted Triphenylphosphonium–Resveratrol Conjugate on Breast Cancer Cells |
| title_fullStr | The Anti-Cancer Effects of Mitochondrial-Targeted Triphenylphosphonium–Resveratrol Conjugate on Breast Cancer Cells |
| title_full_unstemmed | The Anti-Cancer Effects of Mitochondrial-Targeted Triphenylphosphonium–Resveratrol Conjugate on Breast Cancer Cells |
| title_short | The Anti-Cancer Effects of Mitochondrial-Targeted Triphenylphosphonium–Resveratrol Conjugate on Breast Cancer Cells |
| title_sort | anti cancer effects of mitochondrial targeted triphenylphosphonium resveratrol conjugate on breast cancer cells |
| topic | mitochondrial targeting triphenylphosphonium resveratrol breast cancer metabolomics |
| url | https://www.mdpi.com/1424-8247/15/10/1271 |
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