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Indian Journal of Pharmaceutical Education and ResearchNOW IN
Article

Cucurbitacin-B Triggers Fas/FasL-dependent Apoptosis via the Death Receptor Signalling Pathway in Human Breast Cancer Cell Line - MCF-7

Jawaher Amer Alsaiari1, Abdulraheem A. Almalki1, Jawaher Ayidh Alosaimi1, Raja Mohammed Al-Qurashi1, Bedour Abdullah Al-Qurashi1, Fatima Anwar Dhafer1, Ahad Amer Alsaiari1★★ Corresponding author

  1. 1Department of Clinical Laboratory Science, College of Applied Medical Science, Taif University, Taif, SAUDI ARABIA.

CORRESPONDENCE

Ahad Amer Alsaiari

Department of Clinical Laboratory Science, College of Applied Medical Science, Taif University, Taif, SAUDI ARABIA.

ahadamer@tu.edu.sa

Received: 09-03-2026; Revised: 15-05-2026; Accepted: 29-07-2026.

Volume 60, Issue 4S · pp. s1553–s1562 · PUBLISHED 2026 · DOI: 10.5530/ijper.20264032

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ABSTRACT

Background: Globally, Breast Cancer (BC) ranks as the second most common cause of cancer-related death for women. The high mortality and recurrence rates contribute substantially to its fatality. Objectives: This research focused to investigate the anti-cancer potential of Cucurbitacin-B (Cu-B) against the human breast cancer cell line MCF-7, focusing on the Fas/ FasL-mediated death receptor signalling pathway. Materials and Methods: The anti-proliferative effect of Cu-B was assessed using the tetrazolium-based MTT assay, while morphological alterations were observed through phase-contrast microscopy. Apoptotic features were further examined using Acridine Orange/Ethidium Bromide (AO/EtBr) dual staining, and intracellular Reactive Oxygen Species (ROS) levels were quantified with DCFH-DA fluorescence assay. Nuclear alterations were investigated by DNA fragmentation analysis, and FasL gene expression was quantified by qPCR. Results: MTT assay revealed that Cu-B exhibited an IC₅₀ value of 74.836 µg/ mL. Morphological assessment demonstrated pronounced cellular shrinkage and structural disintegration. AO/EtBr staining confirmed an increased proportion of apoptotic cells in Cu-B- treated groups, which was corroborated by the elevated ROS of 7750±901.38 in the treatment group compared to 1333.33±125.83 in the control group, as indicated by DCFH-DA assay. DNA laddering further confirmed nuclear damage, and qPCR analysis showed significant upregulation of FasL expression in treated cells, supporting the activation of death receptor-mediated apoptosis. Conclusion: Cucurbitacin-B demonstrated potent anti-cancer activity against MCF-7 cells. The findings suggest that Cu-B induces apoptosis primarily through the extrinsic pathway by activating Fas/FasL-mediated death receptor signalling.

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    Alsaiari, J. A., Almalki, A. A., Alosaimi, J. A., Al-Qurashi, R. M., Al-Qurashi, B. A., Dhafer, F. A., & Alsaiari, A. A. (2026). Cucurbitacin-B Triggers Fas/FasL-dependent Apoptosis via the Death Receptor Signalling Pathway in Human Breast Cancer Cell Line - MCF-7. Indian Journal of Pharmaceutical Education and Research, 60(4S), s1553–s1562. https://doi.org/10.5530/ijper.20264032