Combinational therapy of tamoxifen and primaquine compound affects GJIC and colony growth in T47D breast cancer cells

4346

Tamoxifen is a synthetic antiestrogen commonly used in the treatment of breast cancer. Tamoxifen is also used as an adjuvant therapy in other malignant tumors which are ER negative. This shows that tamoxifen has other effects besides being antiestrogenic. Gap junctions are cell-cell communication channels allowing the passage of small molecules from one cell to another. Most tumors express less connexins, therefore decreased gap junctions and have increased growth rates compared with non-tumorigenic cells. The enhancement of gap junctions in cancer cells could lead to decrease in the cancerous growth. Previously,we found a decrease in the colony growth using soft agar assay and an increase in the gap junctional activity in the presence of primaquine (PQ1) compound in T47D breast cancer cells. Cancer is a multi-step and multi-stage process involving alterations in multiple pathways at the same time. Therefore, combination therapies are more successful than one drug alone in the treatment of cancer. Currently little work has been done to study the effect of tamoxifen on the gap junctions. The goal of this study is to examine the effect of tamoxifen and PQ1 in combination on the gap junctional activity and colony growth in T47D breast cancer cells. We found a tremendous increase in the gap junctional dye transfer in the presence of 200 nM PQ1 in combination with 10 µM tamoxifen compared to the respective controls. Colony growth assay also showed a 65% decrease in the growth of T47D cells at 200nM PQ1 plus 10 μM tamoxifen compared to 10 μM tamoxifen alone.
 Thus, our results show a promising combinational therapy using primaquine compound (PQ1) and tamoxifen in human breast cancer cells.