Mechanistic Evaluation of Thymoquinone Derivative-Induced Apoptosis in Human Glioblastoma Cells

Background: Glioblastoma is a highly aggressive brain tumor with limited treatment options, necessitating the development of targeted and effective therapeutics. Thymoquinone (TQ), a natural compound with known anticancer potential, has been modified to enhance its efficacy. Materials and Methods: A...

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Main Authors: Manmeet Kour, Jagjeet Kour, Bisma Yousuf, Shashank K. Singh
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2025-06-01
Series:Journal of Pharmacy and Bioallied Sciences
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Online Access:https://journals.lww.com/10.4103/jpbs.jpbs_1967_24
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Summary:Background: Glioblastoma is a highly aggressive brain tumor with limited treatment options, necessitating the development of targeted and effective therapeutics. Thymoquinone (TQ), a natural compound with known anticancer potential, has been modified to enhance its efficacy. Materials and Methods: A series of TQ derivatives (SS-01 to SS-05) and the parent compound (SS-06) were synthesized and screened for cytotoxic activity using the Sulforhodamine B (SRB) assay against various cancer cell lines—glioblastoma (SNB-19, U251), breast carcinoma (MCF-7, MD-MBA-231), pancreatic carcinoma (MIAPaCa, PANC-1), lung carcinoma (A549), prostate carcinoma (PC3)—and a normal fibroblast cell line (FR2). The most promising derivative, SS-03, was further evaluated in U251 glioblastoma cells using colony formation assay, Western blotting for apoptotic markers, and flow cytometry for cell cycle analysis. Results: Among all derivatives, SS-03 exhibited the highest cytotoxicity, particularly against U251 glioblastoma cells. SS-03 treatment significantly increased the Bax/Bcl-2 ratio, induced apoptosis, arrested the cell cycle in S-phase, and suppressed colony formation in a dose-dependent manner. Importantly, SS-03 showed selective toxicity towards cancer cells while sparing normal fibroblasts. Conclusion: SS-03, a novel TQ derivative, demonstrates potent anticancer activity against glioblastoma cells through apoptosis induction and cell cycle arrest.
ISSN:0976-4879
0975-7406