AUTHOR=Alafnan Ahmed , Khalifa Nasrin E. , Hussain Talib , Osman Mhdia Elhadi 

TITLE=Cucurbitacin-B instigates intrinsic apoptosis and modulates Notch signaling in androgen-dependent prostate cancer LNCaP cells

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1206981

DOI=10.3389/fphar.2023.1206981

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> Cytotoxicity evaluation revealed that Cur-B impeded the LNCaP cell’s viability at 5 µM (<italic>p</italic> &lt;0.05) which increased considerably at a concentration of 25 µM (<italic>p</italic> &lt;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 (<italic>p</italic> &lt;0.05) but also in-creased significantly at 25 µM concentration (<italic>p</italic> &lt;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 (<italic>p</italic> &lt;0.001). Cur-B exposure also resulted in the downregulation of cyclin D1, cyclin-dependent kinase 4 (CDK4) followed by amplified levels of p21<sup>Cip1</sup> 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.</p><p><bold>Discussion:</bold> These observations thus, explicitly indicated that Cur-B could be plausibly further explored as potent therapeutics against androgen-dependent PCa.</p>