Chemosensitization of Breast Cancer Cells to Chemotherapeutic Agents by 3,3'diindolylmethane (DIM)

Abstract

Abstract : Constitutive activation of Akt or NF-T B has been reported to play a role in de novo resistance of cancer cells to chemotherapeutic agents, which is a major cause for treatment failure in cancer chemotherapy. Previous studies have shown that 3,3 -diindolylmethane (DIM), a major in vivo acidcatalyzed condensation product of Indole-3-carbinol (I3C), is a potent inducer of apoptosis, inhibitor of tumor angiogenesis and inactivator of Akt/NF- B signaling in breast cancer cells. We found that DIM can inhibit Akt and NF- B in breast cancer cells, suggesting that DIM could sensitize the breast cancer cells to common chemotherapeutic agents. More recently, we found that DIM significantly sensitized the breast cancer cells to Taxotere and Adriamycin. However, little is known regarding the inactivation of Akt/NF- B leading to chemosensitization of breast cancer cells to two of the most common chemotherapeutic agents such as Adriamycin and Taxotere. Based on our preliminary results, we hypothesize that DIM will inactivate Akt and NF- B signaling, thereby sensitizing breast cancer cells to chemotherapeutic agents both in vitro as well as in vivo in an experimental model of breast cancer. The mechanisms for sensitizing the cells may involve down-regulation of the expression of NF- B and its important regulators such as MEKK1, MEK, NIK and IKK genes. We believe that our strategies to sensitize breast cancer cells to the most common chemotherapeutic agents by DIM will be a novel breakthrough for devising optimal therapies for breast cancer.