Curcumin Sensitizes Silymarin to Exert Synergistic Anticancer Activity in Colon Cancer Cells

Abstract

We studied combinatorial interactions of two phytochemicals, curcumin and silymarin, in their action against cancer cell proliferation. Curcumin is the major component of the spice turmeric. Silymarin is a bioactive component of milk thistle used as a protective supplement against liver disease. We studied antiproliferative effects of curcumin alone, silymarin alone and combinations of curcumin and silymarin using colon cancer cell lines (DLD-1, HCT116, LoVo). Curcumin inhibited colon cancer cell proliferation in a concentration-dependent manner, whereas silymarin showed significant inhibition only at the highest concentrations assessed. We found synergistic effects when colon cancer cells were treated with curcumin and silymarin together. The combination treatment led to inhibition of colon cancer cell proliferation and increased apoptosis compared to single compound treated cells. Combination treated cells exhibited marked cell rounding and membrane blebbing of apoptotic cells. Curcumin treated cells showed 3-fold more caspase3/7 activity whereas combination treated cells showed 5-fold more activity compared to control and silymarin treated cells. When DLD-1 cells were pre-exposed to curcumin, followed by treatment with silymarin, the cells underwent a high amount of cell death. The pre-exposure studies indicated curcumin sensitization of silymarin effect. Our results indicate that combinatorial treatments using phytochemicals are effective against colorectal cancer.

Chemoprevention of polyp recurrence with curcumin followed by silibinin in a case of multiple colorectal adenomas

“…It decreases polyp formation in APC Min/+ mice, inhibits cell proliferation, inflammation and angiogenesis, induces apoptosis, decreases beta-catenin levels (3), and targets colorectal cancer stem cells (4). Curcumin sensitizes silymarin to exert a synergistic anticancer activity on colon cancer cells (5). This is to our knowledge, the first case showing that curcumin followed by silibinin decreases colon polyp formation.…”

The Influence of Lycopene, [6]-Gingerol, and Silymarin on the Apoptosis on U-118MG Glioblastoma Cells In Vitro Model

“…Ranjbar et al showed that treatment of Ramos cancer cells with 100 µg/mL of sylimarin markedly increased the activity of caspase-3 [37]. Montgomery et al showed that silymarin at the highest dose of 100 µM/mL has antiproliferative activity in colorectal cancer cell lines: DLD-1, LoVo, and HCT116 [38]. Furthermore, the experiment carried out on the ovarian cell line indicates the inhibitory properties of silymarin: significantly limits the growth and rate of proliferation, inhibits the cell cycle in G1/S phase, and the doses of 50 µg/mL and 100 µg/mL activate the apoptotic pathway and induce cytochrome C release, as well as the reduction of the mitochondrial membrane potential [39].…”

Activation of the CRABPII/RAR pathway by curcumin induces retinoic acid mediated apoptosis in retinoic acid resistant breast cancer cells

“…While they are less toxic and have no side effects, combinatorial treatment of phytochemicals with chemotherapeutic agents can be an alternative method to reduce the dosage of traditional chemotherapeutic regimens and lower cardiac toxicity associated with them (50). Owing to drug resistance in cancer, curcumin has been shown to be an effective adjuvant in reversing chemoresistance and sensitizing cancer cells to chemotherapeutic drugs (41–47,51–54). …”