Phosphatidylserine-targeting bis(zinc-dipicolylamine) farnesol inhibits ATP production in cancer cells to overcome multidrug resistance
Multidrug resistance significantly impedes the efficacy of cancer chemotherapy. Resistance often arises from the reduced cellular uptake of chemotherapeutic drugs, a process crucial for their cytotoxic effects. This reduction is frequently due to transmembrane efflux pumps powered by ATP from mitoch...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2024-12-01
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| Series: | Supramolecular Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667240524000060 |
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| author | Wei Huang Xuan Nie Xiao-Hong Zhou Lei Qiao Hong-Jie Gao Jing Zang Long-Kang Yu Long-Hai Wang Ye-Zi You |
| author_facet | Wei Huang Xuan Nie Xiao-Hong Zhou Lei Qiao Hong-Jie Gao Jing Zang Long-Kang Yu Long-Hai Wang Ye-Zi You |
| author_sort | Wei Huang |
| collection | DOAJ |
| description | Multidrug resistance significantly impedes the efficacy of cancer chemotherapy. Resistance often arises from the reduced cellular uptake of chemotherapeutic drugs, a process crucial for their cytotoxic effects. This reduction is frequently due to transmembrane efflux pumps powered by ATP from mitochondria and the cytoplasmic matrix, leading to lower intracellular concentrations of these drugs. This study introduces an amphiphilic molecule, bis(zinc-dipicolylamine) farnesol (Bis-ZnDPA), which targets phosphatidylserine (PS) – a negatively charged phospholipid prominently displayed on the outer leaflet of cancer cell plasma membranes. Integrating the hydrophobic segment of Bis-ZnDPA into the plasma membrane disrupts its integrity, potentially leading to hole formation and facilitating the uptake of chemotherapeutic drugs. Furthermore, the binding of Bis-ZnDPA to phosphatidylserine inhibits ATP production caused by Ca2+ influx and deregulation of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway, reducing the efflux of drugs from cells. The results indicate the potent synergistic effect of Bis-ZnDPA with chemotherapeutic agents, suggesting that targeting PS is a viable strategy for overcoming multidrug resistance in cancer chemotherapy. |
| format | Article |
| id | doaj-art-68bc7c1ac7614b3f8f4a2ee9a0c87e4a |
| institution | DOAJ |
| issn | 2667-2405 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Supramolecular Materials |
| spelling | doaj-art-68bc7c1ac7614b3f8f4a2ee9a0c87e4a2025-08-20T02:52:58ZengKeAi Communications Co., Ltd.Supramolecular Materials2667-24052024-12-01310006810.1016/j.supmat.2024.100068Phosphatidylserine-targeting bis(zinc-dipicolylamine) farnesol inhibits ATP production in cancer cells to overcome multidrug resistanceWei Huang0Xuan Nie1Xiao-Hong Zhou2Lei Qiao3Hong-Jie Gao4Jing Zang5Long-Kang Yu6Long-Hai Wang7Ye-Zi You8Key Laboratory of Precision and Intelligent Chemistry, University of Science and Technology of China, Hefei, Anhui, China; Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, China; Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Precision Pharmaceutical Preparations and Clinical Pharmacy, Hefei, Anhui, ChinaDepartment of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Precision Pharmaceutical Preparations and Clinical Pharmacy, Hefei, Anhui, ChinaKey Laboratory of Precision and Intelligent Chemistry, University of Science and Technology of China, Hefei, Anhui, China; Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, ChinaKey Laboratory of Precision and Intelligent Chemistry, University of Science and Technology of China, Hefei, Anhui, China; Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, ChinaKey Laboratory of Precision and Intelligent Chemistry, University of Science and Technology of China, Hefei, Anhui, China; Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, ChinaKey Laboratory of Precision and Intelligent Chemistry, University of Science and Technology of China, Hefei, Anhui, China; Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, ChinaKey Laboratory of Precision and Intelligent Chemistry, University of Science and Technology of China, Hefei, Anhui, China; Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, ChinaKey Laboratory of Precision and Intelligent Chemistry, University of Science and Technology of China, Hefei, Anhui, China; Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, China; Corresponding author.Key Laboratory of Precision and Intelligent Chemistry, University of Science and Technology of China, Hefei, Anhui, China; Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, China; Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Precision Pharmaceutical Preparations and Clinical Pharmacy, Hefei, Anhui, ChinaMultidrug resistance significantly impedes the efficacy of cancer chemotherapy. Resistance often arises from the reduced cellular uptake of chemotherapeutic drugs, a process crucial for their cytotoxic effects. This reduction is frequently due to transmembrane efflux pumps powered by ATP from mitochondria and the cytoplasmic matrix, leading to lower intracellular concentrations of these drugs. This study introduces an amphiphilic molecule, bis(zinc-dipicolylamine) farnesol (Bis-ZnDPA), which targets phosphatidylserine (PS) – a negatively charged phospholipid prominently displayed on the outer leaflet of cancer cell plasma membranes. Integrating the hydrophobic segment of Bis-ZnDPA into the plasma membrane disrupts its integrity, potentially leading to hole formation and facilitating the uptake of chemotherapeutic drugs. Furthermore, the binding of Bis-ZnDPA to phosphatidylserine inhibits ATP production caused by Ca2+ influx and deregulation of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway, reducing the efflux of drugs from cells. The results indicate the potent synergistic effect of Bis-ZnDPA with chemotherapeutic agents, suggesting that targeting PS is a viable strategy for overcoming multidrug resistance in cancer chemotherapy.http://www.sciencedirect.com/science/article/pii/S2667240524000060Multidrug resistancePhosphatidylserineZn-dipicolylamine |
| spellingShingle | Wei Huang Xuan Nie Xiao-Hong Zhou Lei Qiao Hong-Jie Gao Jing Zang Long-Kang Yu Long-Hai Wang Ye-Zi You Phosphatidylserine-targeting bis(zinc-dipicolylamine) farnesol inhibits ATP production in cancer cells to overcome multidrug resistance Supramolecular Materials Multidrug resistance Phosphatidylserine Zn-dipicolylamine |
| title | Phosphatidylserine-targeting bis(zinc-dipicolylamine) farnesol inhibits ATP production in cancer cells to overcome multidrug resistance |
| title_full | Phosphatidylserine-targeting bis(zinc-dipicolylamine) farnesol inhibits ATP production in cancer cells to overcome multidrug resistance |
| title_fullStr | Phosphatidylserine-targeting bis(zinc-dipicolylamine) farnesol inhibits ATP production in cancer cells to overcome multidrug resistance |
| title_full_unstemmed | Phosphatidylserine-targeting bis(zinc-dipicolylamine) farnesol inhibits ATP production in cancer cells to overcome multidrug resistance |
| title_short | Phosphatidylserine-targeting bis(zinc-dipicolylamine) farnesol inhibits ATP production in cancer cells to overcome multidrug resistance |
| title_sort | phosphatidylserine targeting bis zinc dipicolylamine farnesol inhibits atp production in cancer cells to overcome multidrug resistance |
| topic | Multidrug resistance Phosphatidylserine Zn-dipicolylamine |
| url | http://www.sciencedirect.com/science/article/pii/S2667240524000060 |
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