Decoding cell death signalling: Impact on the response of breast cancer cells to approved therapies.

Breast cancer is a principal cause of cancer-related mortality in female worldwide. While many approved therapies have shown promising outcomes in treating breast cancer, understanding the intricate signalling pathways controlling cell death is crucial for optimizing the treatment outcome. A growing body of evidence has unveiled the aberrations in multiple cell death pathways across diverse cancer types, highlighting these pathways as appealing targets for therapeutic interventions. In this review, we provide a comprehensive overview of the current state of knowledge on the cell death signalling mechanisms with a particular focus on their impact on the response of breast cancer cells to approved therapies. Additionally, we discuss the potentials of combination therapies that exploit the synergy between approved drugs and therapeutic agents targeting modulators of cell death pathways.

Effect of safranal on the response of cancer cells to topoisomerase I inhibitors: Does sequence matter?

Lung and colorectal cancers are among the leading causes of death from cancer worldwide. Although topotecan (TPT), a topoisomerase1 inhibitor, is a first- and second-line drug for lung and colon cancers, the development of drug resistance and toxicity still remain as a major obstacle to chemotherapeutic success. Accumulating evidence indicates increased efficacy and reduced toxicity of chemotherapeutic agents upon combining them with natural products. We aimed to investigate the possible interaction of safranal (SAF), a natural compound obtained from Crocus sativus stigma, with TPT when used in different sequences in colon and lung cancer cell lines. The growth inhibitory effect of the proposed combination given in different sequences was assessed using the colony formation assay. The comet assay, cell cycle distribution, Annexin-V staining, and expression of proteins involved in DNA damage/repair were utilized to understand the mechanism underlying the effect of the combination. SAF enhanced the growth inhibitory effects of TPT particularly when it was added to the cells prior to TPT. This combination increased the double-strand break induction and dysregulated the DNA repair machinery, particularly the tyrosyl-DNA phosphodiesterase 1 enzyme. In addition, the SAF + TPT combination increased the fraction of cells arrested at the G2/M checkpoint as well as enhanced the induction of apoptosis. The current study highlights the status of SAF as a natural product sensitizing the lung and colon cancer cells to the cytotoxic effects of the anticancer drug TPT. In addition, it emphasizes the importance of sequence-dependent interaction which can affect the overall outcome.