In vitro additive antitumor effects of dimethoxycurcumin and 5-fluorouracil in colon cancer cells.

Abstract

Dimethoxycurcumin (DMC) is a lipophilic analog of curcumin, an effective treatment for colon cancer, which has greater chemical and metabolic stability. Chemotherapy treatments, such as 5‐fluorouracil (5‐Fu), play a key role in the current management of colon cancer. In this study, we investigated the antitumor efficacy of DMC in combination with 5‐Fu in SW480 and SW620 colon cancer cells. CCK‐8 assay was used to evaluate the inhibitory effect of DMC and 5‐Fu on cancer cells proliferation, and the combination index was calculated. The influence of DMC and 5‐Fu on cell cycle, apoptosis, reactive oxygen species (ROS) production, and mitochondrial membrane potential in SW480 and SW620 cells was determined using flow cytometry, and the related signaling pathways were detected by western blot. Transmission electron microscopy was used to observe endoplasmic reticulum expansion. DMC‐ and/or 5‐Fu‐induced apoptosis, stimulated G0/G1 phase arrest, increased ROS levels, decreased mitochondrial membrane potential, and enhanced endoplasmic reticulum expansion. The induction of apoptosis is involved in the increasing of Bax and cytochrome c and decreasing of Bcl2 expressions. Increased production of ROS was accompanied by upregulation of CHOP and Noxa. Combination therapy of DMC and 5‐Fu had increased efficacy on the above pathways compared with either drug alone. Based on the calculated IC 50, combination treatment with DMC and 5‐Fu had an additive antitumor effect in both cell lines. Combined treatment with DMC and 5‐Fu led to an additive antitumor effect in colon cancer cells that was related to apoptosis induction, G0/G1 phase arrest, increased ROS production, decreased mitochondrial membrane potential, and enhanced endoplasmic reticulum expansion.