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β-Sitosterol Synergizes Cisplatin's Anti-Lung Cancer Activity: A Cell Line Study | ||
| Al- Anbar Medical Journal | ||
| Volume 21, Issue 3, July 2025, Pages 171-178 PDF (1.21 M) | ||
| Document Type: Original articles | ||
| DOI: 10.33091/amj.2025.157207.2106 | ||
| Authors | ||
| Wisam Hussein Selman* 1; Noora Kadhim Hadi Alyasari1; Hassan Al-Karagoly2, 3 | ||
| 1Department of Physiology, Pharmacology, and Biochemistry, College of Veterinary Medicine, University of Al-Qadisiyah, Al-Diwaniyah, Iraq. | ||
| 2Department of Internal and Preventive Medicine, College of Veterinary Medicine, University of Al-Qadisiyah, Al-Diwaniyah, Iraq. | ||
| 3Department of Clinical Laboratory Sciences, College of Pharmacy, Alayen Iraqi University, Thi-Qar 64001, Iraq. | ||
| Abstract | ||
| Background: Cisplatin (Cis) is the primary chemotherapeutic agent for treating non-small cell lung cancer (NSCLC). β-sitosterol (Bs), a plant-derived polyphenol, inhibits tumor proliferation in several malignancies. Objectives: To evaluate whether Bs in combination with Cis (BCcomb) enhance Cis' anticancer activity against NSCLC cells. Additionally, it investigated the possibility of lowering the Cis dosage when combined with Bs in the treatment of NSCLC. Methods: The study, conducted in 2024, utilized the A549 cell line as an NSCLC model, with control and three treatment groups (Bs, Cis, and BCcomb). Cell viability was assessed via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and trypan blue exclusion assays. Bs-Cis interaction was analyzed using a combination index, isobologram, and Bliss independence model. The dose reduction index was also used to predict a dose reduction for Bs and Cis in the combination. Expression of apoptotic-related genes (p53, BAX, BCL-2, MCL-1) and the activities of both caspase 3/7 and reactive oxygen species (ROS) were quantified. Results: This study is the first to demonstrate that Bs, in combination with Cis, significantly synergizes to suppress NSCLC cells, enabling lower doses of Bs or Cis in the BCcomb without reducing efficacy. The combination of Bs with Cis markedly enhances their cytotoxic efficacy, as evidenced by the activation of apoptotic markers and elevated intracellular ROS generation, demonstrating the superiority of the BCcomb compared to Bs or Cis monotherapy. Conclusion: This study provides evidence that BCcomb may hold promise as a prospective therapeutic strategy for clinically improving NSCLC treatment outcomes. | ||
| Keywords | ||
| Lung cancer; Cisplatin; β-sitosterol; Apoptosis; Synergism | ||
| References | ||
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