Differential modulation of cisplatin efficacy by montelukast sodium and desloratadine in lung cancer
Year: 2025
Type: article
Abstract: Background/aim: Despite advances in treatment, achieving effective and durable responses with chemotherapy remains a significant challenge in lung cancer management. This study investigates the effects of montelukast sodium (MLS) and desloratadine (DES), alone and in combination with cisplatin (CIS), on cell viability, apoptosis, cell cycle distribution, and antioxidant gene expression in A549 and DMS114 lung cancer cell lines. Materials and methods: Cells were treated with CIS, MLS, DES, and their combinations for 24–72 h. Cell viability was assessed via MTS assay; apoptosis and cell cycle progression were analyzed by flow cytometry. The expression of antioxidant-related genes (GPX4, GSR, GCLC) was quantified using qRT-PCR. Results: MLS and DES reduced cell viability individually in both cell lines in a dose- and time-dependent manner. The combination of CIS and MLS showed near-synergistic effects in A549 cells. The combination significantly enhanced apoptosis, particularly in DMS114 cells. In contrast, CIS combined with DES showed antagonistic interactions in both lines, with no significant increase in apoptosis compared to CIS alone. MLS combined with CIS also enhanced G0/G1 phase arrest, while the combination of DES and CIS had no additive effect on the cell cycle. DES alone or with CIS significantly upregulated GPX4 and GCLC, suggesting activation of antioxidant defense mechanisms. Meanwhile, MLS alone or combined with CIS led to a decrease in GCLC expression, indicating a possible impairment of redox homeostasis. Conclusion: MLS enhances CIS-induced cytotoxicity and apoptosis in lung cancer cells and modulates redox gene expression, potentially improving therapeutic efficacy. In contrast, DES may attenuate CIS activity through antioxidant gene upregulation. These findings support the potential of MLS as an effective adjuvant in CIS-based lung cancer treatment. However, the antagonistic effect observed with DES highlights the importance of careful evaluation of candidates for drug repurposing.
Source: TURKISH JOURNAL OF BIOLOGY
Institution: Yeditepe University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4415834818
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