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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Selective Estrogen Receptor Modulators (SERMs) Synergize with Cisplatin, Induce Apoptosis and Suppress Cellular Migration and Colony Formation of Lung Cancer Cells

Author(s): Lina Alsous and Sanaa Bardaweel*

Volume 22, Issue 9, 2022

Published on: 04 January, 2022

Page: [1826 - 1836] Pages: 11

DOI: 10.2174/1871520621666210908110902

Price: $65

Abstract

Background: Lung cancer remains the leading cause of cancer-related deaths worldwide. Hence, novel therapeutic approaches targeting crucial pathways are needed to improve its treatment. Previous studies have verified the involvement of the estrogen pathway, mediated through estrogen receptor β (ERβ), in the development and progression of lung carcinogenesis. Selective estrogen receptor modulators (SERMs) are a group of estrogen receptor agonists/antagonists that have tissue selective effects. Many of the available SERMs are used for the management of breast cancer. However, their role in lung cancer is still under investigation.

Objectives: The aim of this research is to investigate the anti-tumorigenic activity of the selective estrogen receptor modulators, tamoxifen, raloxifene, and toremifene, against different lung cancer cell lines.

Methods: The anti-proliferative and combined effects of SERMs with standard chemotherapy were evaluated by MTT assay. Cell migration was assessed using a wound-healing assay. The mechanism of cell death was determined using the Annexin V-FITC/ propidium iodide staining flow cytometry method. Cells’ capability to form colonies was evaluated by soft agar colony formation assay. Estrogen receptors expression was determined using real-time PCR.

Results: Our results have demonstrated the presence of ERβ in A549, H1299, and H661 lung cancer cells. Cellular proliferation assay suggested that SERMs have significantly reduced lung cancer cells proliferation in a time and concentration- dependent manner. Additionally, SERMs exhibited a synergistic effect against A549 cells when combined with cisplatin. SERMs treatment have increased cell apoptosis and resulted in concentration-dependent inhibition of cell migration and colony formation of A549 cells.

Conclusion: Selective estrogen receptor modulators may possess potential therapeutic utility for the treatment of lung cancer as monotherapy or in combination with standard chemotherapy.

Keywords: Selective estrogen receptor modulators, estrogen receptors, lung cancer, proliferation, apoptosis, metastasis.

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