Insights on possible interplay between epithelial-mesenchymal transition and T-type voltage gated calcium channels genes in metastatic breast carcinoma.

Breast cancer (BC) is the most common life-threatening malignancy amongst women with high incidence worldwide. In Egypt, it is the most known malignancy amongst females. Epithelial-mesenchymal transition (EMT) participates in breast tumors' invasiveness, and metastasis, but the process is poorly understood. The involvement of voltage-gated calcium channels signaling in EMT has not yet been fully explored. Therefore, the aim of this study was to investigate the possible role of T-type calcium channels in metastasis and EMT among breast cancer patients. The study was carried out on 48 female breast cancer patients who were divided into two groups; metastatic and non-metastatic. qRT-PCR was employed to measure the expression of EMT marker genes (N- cadherin, E-cadherin, Snail, Vimentin and T-type VGCCs genes (CACNA1G, CACNA1H, and CACNA1I). The results of the present study revealed differential expression of the EMT marker genes in blood and tissue of non-metastatic and metastatic breast cancer patients, with a clear tendency for the mesenchymal markers to be significantly elevated in metastatic patients as well as malignant tissues taken from non-metastatic patients as compared to their paired tumor adjacent normal (TAN) tissue. Both CACNA1H and CACNA1I (T-type VGCCs oncogenes) were significantly elevated in blood of metastatic patients when compared to non-metastatic ones. In contrast, CACNA1G (tumor suppressor) exhibited a significant decrease in metastatic patients. The strong correlation between the expression of T-type VGCCs and mesenchymal marker genes in metastatic breast cancer patients casts light on the role of T-type VGCCs in metastasis and their involved in tumor invasiveness.

Cytotoxic, chemosensitizing and radiosensitizing effects of curcumin based on thioredoxin system inhibition in breast cancer cells: 2D vs. 3D cell culture system.

Targeting the thioredoxin/thioredoxin reductase (Trx/TrxR) system is a promising strategy to overcome cancer resistance to conventional therapy. The present study investigated the effect of curcumin on the Trx/TrxR system either alone or in combination with chemotherapy, or radiotherapy in human MCF-7 breast cancer cells seeded in 2 and 3D culture systems. Cell viability, thioredoxin reductase 1 (TrxR1) activity, and the genetic expression of Trx, TrxR1, Bcl2 and BAX genes were studied. The findings showed that the mode of culture significantly affected the response of cancer cells to different treatment modalities, as well as their gene expression patterns. Curcumin treatment resulted in a reduction of breast cancer cell proliferation and induction of apoptosis, an effect that may be mediated by manipulating Trx system components, mainly Trx expression, and to a lesser extent TrxR1 expression and concentration. Furthermore, curcumin increased the sensitivity of breast cancer cells to chemotherapy and radiotherapy by reducing Trx and TrxR1 expression levels. Thus, curcumin may have a potential role as a dose-modifying agent that can be used either to sensitize resistant cells to therapy or to reduce the dose of these therapeutic agents.