Chronic treatment with TNF-α, alone and in combination with Takinib, SB203580 and metformin induce cell death in breast cancer

• Published in: Heliyon 2023-11, Vol.9 (11), p.e21060-e21060, Article e21060
• Main Authors: Abdolvand, Maryam, Shahini Shams Abadi, Milad, Soltani, Amin, Banisharif, Fatemeh, Ghatrehsamani, Mahdi
• Format: Article
• Language: English
• Subjects: BCSC; Breast cancer; Metformin; SB203580; TAK1; Takinib; TNF-α
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2023.e21060

Breast cancer (BC) is the most common malignancy, and the largest cause of cancer death among women. The interactions between tumor cells and tumor micro environmental factors have a major impact on tumor progression. One of the critical pro-inflammatory cytokines present in breast cancer tumor microenvironment is TNF-α. The aim of this study was to evaluate the long-term effect of TNF-α (1 week) along with p38 or TAK1 inhibitors as well as metformin on induction of cellular death, cancer stem cell and expression of metastatic marker CXCR4. MCF-7 and MDA-MB-231 cells were treated with TNF-α for one week and then were treated with combination of Takinib, SB203580 or Metformin; after all treatments were done, cell proliferation, cellular death, surface expression of CXCR4, CD44 and CD24 were determined. The results showed that treatment with TNF-α alone or in combination with Takinib, SB203580 and metformin elevated induction of cellular death in both cell lines compared to the control group. TNF-α also increased CXCR4 expression in MCF-7 cells, but it reduced its expression in the MDA-MB-231 cells. Also, breast cancer stem cells (BCSCs) population decreased in MDA-MB-231 cells treated with TNF-α alone or in combination with SB203580 and metformin. Although, in MCF-7 cells only combination of TNF-α and Takinib reduced BCSCs population in a time dependent manner. Altogether, we showed that TNF-α alone or in combination with other treatments can affect the progression of breast cancer.