The Effects of Nebivolol-Gefitinib-Loratadine Against Lung Cancer Cell Lines
José Luis Martínez-Lira1,2, Elisabeth Hernández-Gallegos1, María DE Guadalupe Chávez-López1
1Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav-IPN), Ciudad de México, México.
Background/Aim:
Non-small-cell lung cancer (NSCLC) is the most frequently diagnosed malignancy and the first cause of cancer-related death. Thus, finding alternative therapeutic options is crucial. Drug repurposing offers therapeutic options in a simplified and affordable manner, especially to cancer patients in developing countries. Several drugs including antihistamines and beta-adrenergic receptor blockers (beta-blockers) display antiproliferative properties on cancer cells. Interestingly, NSCLC patients who had used either antihistamines or beta-blockers showed improved response to chemotherapy or reduced mortality in comparison to non-users of any of these drugs. However, combination therapy is gaining substantial interest in many cancers including non-EGFR mutated NSCLC. Here, we investigated the antineoplastic effect of the combination of the antihistamine loratadine, the beta-blocker nebivolol, and the tyrosine-kinase inhibitor gefitinib on NSCLC cell lines.
Materials And Methods:
A-549 and NCI-H1975 cell lines were used. The effect of nebivolol, gefitinib, and loratadine on the metabolic activity was studied using the MTT assay. The inhibitory concentrations (IC20 and IC50) were calculated and used in the drug-combination experiments. Apoptosis was investigated using flow cytometry; and cell survival using the colony formation assay.
Results:
The combination nebivolol-loratadine-gefitinib produced a significant synergistic effect on inhibiting the metabolic activity and colony formation, as well as on promoting apoptosis in both cell lines. Noteworthy, the effect on the cell line carrying the EGFR mutation (NCI-H1975) was very similar to the cell line that does not exhibit such mutation (A-549 cells).
Conclusion:
The nebivolol-gefitinib-loratadine combination may be a promising alternative for lung cancer treatment.
Insights
This study shows that combining loratadine, nebivolol, and gefitinib effectively inhibits non-small-cell lung cancer (NSCLC) cell growth and promotes cell death. This drug combination may offer a new treatment option for lung cancer.
Area of Science:
- Oncology
- Pharmacology
- Drug Discovery
Background:
- Non-small-cell lung cancer (NSCLC) is a leading cause of cancer death, necessitating novel therapeutic strategies.
- Drug repurposing presents an affordable approach to cancer treatment, particularly in resource-limited settings.
- Antihistamines and beta-blockers have demonstrated antiproliferative effects, with some evidence suggesting improved outcomes in NSCLC patients using these drug classes.
Purpose of the Study:
- To investigate the antineoplastic effects of combining loratadine (antihistamine), nebivolol (beta-blocker), and gefitinib (tyrosine-kinase inhibitor) in NSCLC cell lines.
- To evaluate the synergistic potential of this drug combination in non-small-cell lung cancer treatment.
- To assess the efficacy of the combination therapy irrespective of EGFR mutation status.
Main Methods:
- Utilized A-549 and NCI-H1975 non-small-cell lung cancer cell lines.
- Assessed metabolic activity using the MTT assay to determine IC20 and IC50 values for combination experiments.
- Investigated apoptosis via flow cytometry and cell survival through colony formation assays.
Main Results:
- The combination of nebivolol, loratadine, and gefitinib demonstrated significant synergistic effects in inhibiting metabolic activity and colony formation.
- This drug combination effectively promoted apoptosis in both tested NSCLC cell lines.
- The observed synergistic effects were consistent across cell lines with and without EGFR mutations.
Conclusions:
- The combination of nebivolol, gefitinib, and loratadine shows promise as a novel therapeutic strategy for non-small-cell lung cancer.
- This drug combination may offer a viable and effective treatment option for lung cancer patients.
- The synergistic activity observed suggests potential for combination therapy in NSCLC, regardless of EGFR mutation status.
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