This study investigated how histone deacetylase (HDAC) inhibition affects tamoxifen treatment. Breast cancer cells use autophagy as a survival mechanism in response to nutrient starvation, exposure to DNA damaging agents, and tamoxifen treatment. Autophagy is a type of cell self-digestion which can stop normal cells from developing into cancer cells and lead to cell death. However, autophagy can also protect cancer cells, as is the case for breast cancer in the circumstances outlined above. HDAC inhibitors appear to enhance tamoxifen treatment in increasing breast cancer cell death by altering autophagy.
Patients with estrogen receptor-positive (ER+) breast cancer eventually develop resistance to tamoxifen. When autophagy is inhibited in such cells, the cytotoxicity of tamoxifen is enhanced. In the current study, several HDAC inhibitors were found to cause a synergistic increase in apoptosis and cell death in combination with tamoxifen. HDAC inhibitors were found to act synergistically with tamoxifen to prevent the excess of autophagic lysosomes from sustaining self-preservation, thereby triggering elimination of cells by apoptotic cell death in a fatal switch. The authors conclude that combining tamoxifen with an HDAC inhibitor may represent a new therapeutic approach to overcome hormone therapy resistance.
Implications for diet during tamoxifen treatment
Sulforaphane, an isothiocyanate found in cruciferous vegetables, has been shown inhibit the growth of carcinogen-induced mammary tumors in rats. Sulforaphane has also been found to inhibit HDAC activity, among other anti-cancer activities. This suggests that patients taking tamoxifen for breast cancer prevention or treatment might benefit from consuming cruciferous vegetables:
We recommend consuming sulforaphane as a component of food and against consuming it in supplement form. The anticancer properties of cruciferous vegetables are likely to be the result of synergistic interaction of various chemical components - isolated components have successfully inhibited proliferation in the laboratory, but their efficacy and safety in humans needs to be evaluated in large scale clinical trials.