HER2+ breast cancer cells undergo apoptosis upon exposure to tannic acid released from remodeled cross-linked collagen type I.

Tannic acid (TA) is a naturally occurring polyphenol that cross-links collagen type I and possesses anticancer potential. In previous studies, we demonstrated the increased sensitivity of estrogen receptor-positive (ER+ ) breast cancer cells to TA as opposed to triple negative breast cancer cells and normal human breast epithelial cells. In the current study, human pre-adipocytes and HER2+ breast cancer cells were grown on TA cross-linked collagen type I beads. Cell attachment, growth, and proliferation of the cells result in remodeling of the collagen matrix and release of the cross-linking TA. TA concentrations in the conditioned media were determined. Induced apoptosis of cells grown on the TA cross-linked collagen type I beads was imaged and quantified. Viability of HER2+ breast cancer cells and normal breast epithelial cells after exposure TA released from bead remodeling was quantified. Caspase gene expression and protein expression were evaluated. HER2+ breast cancer cells underwent caspase-mediated apoptosis in response to TA exposure. TA-induced apoptosis in a concentration- and time-dependent manner, with HER2+ breast cancer cells demonstrating an increased sensitivity to the TA effects.