Hydroxychloroquine interaction with phosphoinositide 3-kinase modulates prostate cancer growth in bone microenvironment : In vitro and molecular dynamics based approach
Copyright © 2024 Elsevier B.V. All rights reserved..
Patients with advanced prostate cancer (PCa) are more likely to develop bone metastases. Tumor cells thrive in the bone microenvironment, interacting with osteoblasts and osteoclasts. Given the PI3K/AKT pathway's metastatic potential and signal integration's ability to modulate cell fates in PCa development, drugs targeting this system have great therapeutic promise. Hydroxychloroquine (HCQ) is an anti-malarial medication commonly used to treat clinical conditions such as rheumatology and infectious disorders. We explored the anti-neoplastic effect of HCQ on PC3 and C4-2B cell lines in the bone microenvironment. Interestingly, HCQ treatment substantially decreases the viability, proliferation, and migration potential of PCa cells in the bone microenvironment. HCQ induces apoptosis and cell cycle arrest, even in the presence of osteoblast-secreted factors. Mechanistically, HCQ inhibited the activity of the PI3K/AKT signaling pathway, which ultimately regulates the proliferation and migration of PCa cells in the bone. The binding energy for docking HCQ with PI3K was -6.7 kcal/mol, and the complex was stabilized by hydrogen bonds, hydrophobic forces, and van der Waals forces. Molecular simulations further validated the structural integrity of the HCQ-PI3K complex without altering PI3K's secondary structure. Our findings underscore the efficacy of HCQ as a potential therapeutic agent in treating PCa.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:266 |
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| Enthalten in: |
International journal of biological macromolecules - 266(2024), Pt 1 vom: 20. März, Seite 130912 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Abdullah, K M [VerfasserIn] |
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| Links: |
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| Themen: |
Bone metastasis |
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| Anmerkungen: |
Date Revised 03.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.ijbiomac.2024.130912 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370034686 |
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| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a Patients with advanced prostate cancer (PCa) are more likely to develop bone metastases. Tumor cells thrive in the bone microenvironment, interacting with osteoblasts and osteoclasts. Given the PI3K/AKT pathway's metastatic potential and signal integration's ability to modulate cell fates in PCa development, drugs targeting this system have great therapeutic promise. Hydroxychloroquine (HCQ) is an anti-malarial medication commonly used to treat clinical conditions such as rheumatology and infectious disorders. We explored the anti-neoplastic effect of HCQ on PC3 and C4-2B cell lines in the bone microenvironment. Interestingly, HCQ treatment substantially decreases the viability, proliferation, and migration potential of PCa cells in the bone microenvironment. HCQ induces apoptosis and cell cycle arrest, even in the presence of osteoblast-secreted factors. Mechanistically, HCQ inhibited the activity of the PI3K/AKT signaling pathway, which ultimately regulates the proliferation and migration of PCa cells in the bone. The binding energy for docking HCQ with PI3K was -6.7 kcal/mol, and the complex was stabilized by hydrogen bonds, hydrophobic forces, and van der Waals forces. Molecular simulations further validated the structural integrity of the HCQ-PI3K complex without altering PI3K's secondary structure. Our findings underscore the efficacy of HCQ as a potential therapeutic agent in treating PCa | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Bone metastasis | |
| 650 | 4 | |a Bone microenvironment | |
| 650 | 4 | |a Hydroxychloroquine | |
| 650 | 4 | |a PI3K/AKT | |
| 650 | 4 | |a Prostate cancer | |
| 700 | 1 | |a Sharma, Gunjan |e verfasserin |4 aut | |
| 700 | 1 | |a Qais, Faizan Abul |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Imran |e verfasserin |4 aut | |
| 700 | 1 | |a Takkar, Simran |e verfasserin |4 aut | |
| 700 | 1 | |a Kaushal, Jyoti B |e verfasserin |4 aut | |
| 700 | 1 | |a Kanchan, Ranjana K |e verfasserin |4 aut | |
| 700 | 1 | |a Sarwar, Tarique |e verfasserin |4 aut | |
| 700 | 1 | |a Chakravarti, Bandana |e verfasserin |4 aut | |
| 700 | 1 | |a Siddiqui, Jawed A |e verfasserin |4 aut | |
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