Cucurbitacin-B instigates intrinsic apoptosis and modulates Notch signaling in androgen-dependent prostate cancer LNCaP cells
Introduction: Among numerous triterpenoids of the Cucurbitaceae family, Cucurbitacin-B (Cur-B) is being explored for its pharmacological attributes. Reports from previous studies have explicitly shown that Cur-B possesses substantial anticancer effects. The present report focuses on exploring the an...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1206981/full |
| _version_ | 1797671366584958976 |
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| author | Ahmed Alafnan Nasrin E. Khalifa Nasrin E. Khalifa Talib Hussain Mhdia Elhadi Osman |
| author_facet | Ahmed Alafnan Nasrin E. Khalifa Nasrin E. Khalifa Talib Hussain Mhdia Elhadi Osman |
| author_sort | Ahmed Alafnan |
| collection | DOAJ |
| description | Introduction: Among numerous triterpenoids of the Cucurbitaceae family, Cucurbitacin-B (Cur-B) is being explored for its pharmacological attributes. Reports from previous studies have explicitly shown that Cur-B possesses substantial anticancer effects. The present report focuses on exploring the anticancer attributes of Cur-B against androgen-dependent PCa LNCaP cells.Methods: LNCaP cells were exposed to commercially available purified Cur-B at varying concentrations that were selected as 5, 10, 15, 20, and 25 µM for some time of 24 h to perform various experimental studies.Results: Cytotoxicity evaluation revealed that Cur-B impeded the LNCaP cell’s viability at 5 µM (p <0.05) which increased considerably at a concentration of 25 µM (p <0.001). Cur-B was also efficacious in inducing the changes within nu-clear morphology followed by a concomitant increase in the activities of key caspases including caspase-3, -8, and -9 intriguingly in a dose-dependent trend. Cur-B treatment not only resulted in the augmentation of intracellular ROS levels within LNCaP cells at 5 µM (p <0.05) but also in-creased significantly at 25 µM concentration (p <0.001). Elevation in the ROS levels was also found to be correlated with dissipated mitochondrial membrane potential (ΔΨm) which culminated in the onset of significant apoptosis at 25 µM concentration (p <0.001). Cur-B exposure also resulted in the downregulation of cyclin D1, cyclin-dependent kinase 4 (CDK4) followed by amplified levels of p21Cip1 mRNA. Importantly, exposure of Cur-B competently reduced the expression of the Notch signaling cascade which may be the plausible cause behind Cur-B-instigated apoptotic cell death and cell cycle arrest in LNCaP cells.Discussion: These observations thus, explicitly indicated that Cur-B could be plausibly further explored as potent therapeutics against androgen-dependent PCa. |
| first_indexed | 2024-03-11T21:14:21Z |
| format | Article |
| id | doaj.art-ee23ee77dcc54f2ea1c3ecc1c379c449 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-11T21:14:21Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-ee23ee77dcc54f2ea1c3ecc1c379c4492023-09-29T06:14:57ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-06-011410.3389/fphar.2023.12069811206981Cucurbitacin-B instigates intrinsic apoptosis and modulates Notch signaling in androgen-dependent prostate cancer LNCaP cellsAhmed Alafnan0Nasrin E. Khalifa1Nasrin E. Khalifa2Talib Hussain3Mhdia Elhadi Osman4Department of Pharmacology and Toxicology, College of Pharmacy, University of Ha’il, Ha’il, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, University of Ha’il, Ha’il, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum, SudanDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Ha’il, Ha’il, Saudi ArabiaDepartment of Clinical Pharmacy, College of Pharmacy, University of Ha’il, Ha’il, Saudi ArabiaIntroduction: Among numerous triterpenoids of the Cucurbitaceae family, Cucurbitacin-B (Cur-B) is being explored for its pharmacological attributes. Reports from previous studies have explicitly shown that Cur-B possesses substantial anticancer effects. The present report focuses on exploring the anticancer attributes of Cur-B against androgen-dependent PCa LNCaP cells.Methods: LNCaP cells were exposed to commercially available purified Cur-B at varying concentrations that were selected as 5, 10, 15, 20, and 25 µM for some time of 24 h to perform various experimental studies.Results: Cytotoxicity evaluation revealed that Cur-B impeded the LNCaP cell’s viability at 5 µM (p <0.05) which increased considerably at a concentration of 25 µM (p <0.001). Cur-B was also efficacious in inducing the changes within nu-clear morphology followed by a concomitant increase in the activities of key caspases including caspase-3, -8, and -9 intriguingly in a dose-dependent trend. Cur-B treatment not only resulted in the augmentation of intracellular ROS levels within LNCaP cells at 5 µM (p <0.05) but also in-creased significantly at 25 µM concentration (p <0.001). Elevation in the ROS levels was also found to be correlated with dissipated mitochondrial membrane potential (ΔΨm) which culminated in the onset of significant apoptosis at 25 µM concentration (p <0.001). Cur-B exposure also resulted in the downregulation of cyclin D1, cyclin-dependent kinase 4 (CDK4) followed by amplified levels of p21Cip1 mRNA. Importantly, exposure of Cur-B competently reduced the expression of the Notch signaling cascade which may be the plausible cause behind Cur-B-instigated apoptotic cell death and cell cycle arrest in LNCaP cells.Discussion: These observations thus, explicitly indicated that Cur-B could be plausibly further explored as potent therapeutics against androgen-dependent PCa.https://www.frontiersin.org/articles/10.3389/fphar.2023.1206981/fullanti-cancerapoptosiscell cyclecucurbitacin-BNotch signaling |
| spellingShingle | Ahmed Alafnan Nasrin E. Khalifa Nasrin E. Khalifa Talib Hussain Mhdia Elhadi Osman Cucurbitacin-B instigates intrinsic apoptosis and modulates Notch signaling in androgen-dependent prostate cancer LNCaP cells Frontiers in Pharmacology anti-cancer apoptosis cell cycle cucurbitacin-B Notch signaling |
| title | Cucurbitacin-B instigates intrinsic apoptosis and modulates Notch signaling in androgen-dependent prostate cancer LNCaP cells |
| title_full | Cucurbitacin-B instigates intrinsic apoptosis and modulates Notch signaling in androgen-dependent prostate cancer LNCaP cells |
| title_fullStr | Cucurbitacin-B instigates intrinsic apoptosis and modulates Notch signaling in androgen-dependent prostate cancer LNCaP cells |
| title_full_unstemmed | Cucurbitacin-B instigates intrinsic apoptosis and modulates Notch signaling in androgen-dependent prostate cancer LNCaP cells |
| title_short | Cucurbitacin-B instigates intrinsic apoptosis and modulates Notch signaling in androgen-dependent prostate cancer LNCaP cells |
| title_sort | cucurbitacin b instigates intrinsic apoptosis and modulates notch signaling in androgen dependent prostate cancer lncap cells |
| topic | anti-cancer apoptosis cell cycle cucurbitacin-B Notch signaling |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1206981/full |
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