Cellular and Molecular Effects of the Dietary Phytochemical Piperine on Triple-Negative Breast Cancer Cells

Triple-negative breast cancers represent an unusually aggressive and difficult to treat form of the disease. Although chemotherapy is the treatment of choice, chemotherapeutic drugs may cause secondary cancers to develop and also have harmful side effects since these drugs kill any rapidly growing cells, including healthy cells of the immune system and cells that line the intestine. In addition, triple-negative breast cancers often become resistant to chemotherapeutic drugs and are not affected by hormonal therapy or targeted therapy with Herceptin. For these reasons, new anticancer drugs that only kill breast cancer cells and are effective against triple-negative breast cancer cells are urgently needed. In this regard, certain plant-derived dietary substances are able to kill both drug-sensitive and -resistant cancer cells without harming their healthy counterparts. We have discovered that piperine from the spice black pepper triggers a form of cell death known as apoptosis in breast cancer cells, including triple-negative breast cancer cells, without harming healthy breast cells. Piperine is also able to combine with ionizing radiation or chemotherapeutic drugs for better killing of breast cancer cells. Our research will determine how piperine kills triple-negative breast cancer cells and prevents their spread, as well as establish the effectiveness of a nanoparticle-based delivery system for piperine in a mouse model of triple-negative breast cancer. These studies will provide a sound rationale for the possible application of piperine in the treatment of metastatic disease caused by triple-negative breast cancer cells. Determine the molecular targets of piperine in triple-negative breast cancer cellsA detailed understanding of the molecular basis for piperine-induced growth inhibition and apoptosis in triple-negative breast cancer cells will inform the rational design of piperine-based monotherapy or combination therapy with other cytotoxic agents.Determine the effect of piperine on metastatic properties of triple-negative breast cancer cellsThis knowledge will provide a rationale for the possible use of piperine to prevent metastasis in patients with triple-negative breast cancer.Establish the effectiveness of a nanoparticle-based delivery system for administration of piperine to mice bearing triple-negative breast cancer xenograftsResults gained from mouse models of breast cancer will provide a strong rationale for further exploration of the possible use of nanoparticle-delivered piperine as an adjunct treatment for triple-negative breast cancer.