Visible light potentiates rapid cell destruction and death by curcumin in vitro.

Abstract

Curcumin, a small molecule derived from the plant Curcuma longa, is a pleiotropic agent with widely varying pharmacological activities attributed to it. In addition to its anti-cancer activity curcumin is also known to be cytotoxic upon photoactivation. Time-lapse DIC and correlative fluorescence microscopy were used to evaluate the effects of curcumin, combined with continuous exposure to visible light, on cellular components of RTG-2 cells. Curcumin combined with visible light resulted in rapid and dramatic destruction of cells. F-actin and microtubule cytoskeletons were drastically altered, both showing fragmentation and overall loss from cells. Nuclei exhibited granulated nucleoplasm, condensed DNA, and physical shrinkage. Mitochondria rapidly fragmented along their length and disappeared from cells. Plasma membrane was breached based on lipophilic dye staining and the entrance of otherwise impermeant small molecules into the cell. Grossly distorted morphology hallmarked by significant swelling and coarse granulation of the cytoplasm was consistently observed. All of these effects were dependent on visible light as the same cellular targets in curcumin-treated cells outside the illuminated area were always unperturbed. The combination of curcumin and continuous exposure to visible light enables rapid and irreversible cellular destruction which can be monitored in real-time. Real-time monitoring of this structural disintegration suggests a new approach to applying curcumin in photodynamic treatments, where the progression of cell and tissue destruction might be simultaneously evaluated through optical means.