Synergistic Inhibitory Effects of Curcumin and 5-Fluorouracil on the Growth of the Human Colon Cancer Cell Line HT-29

Abstract

The synergistic effect of combination treatment with COX-2 inhibitors and chemotherapy may be another promising therapy regimen in the future treatment of colorectal cancer. Curcumin, a major yellow pigment in turmeric which is used widely allover the world, inhibits the growth of human colon cancer cell line HT-29 significantly and specifically inhibits the expression of COX-2 protein. However, the worldwide exposure of populations to curcumin raised the question of whether this agent would enhance or inhibit the effects of chemotherapy. In this report, we evaluated the growth-inhibitory effect of curcumin and a traditional chemotherapy agent, 5-FU, against the proliferation of a human colon cancer cell line (HT-29). The combination effect was quantitatively determined using the method of median-effect principle and the combination index. The inhibition of COX-2 expression after treatment with the curcumin-5-FU combination was also evaluated by Western blot analysis. The IC₅₀ value in the HT-29 cells for curcumin was 15.9 ± 1.96 µM and for 5-FU it was 17.3 ± 1.85 µM. When curcumin and 5-FU were used concurrently, synergistic inhibition of growth was quantitatively demonstrated. The level of COX-2 protein expression was reduced almost 6-fold after the combination treatment. Our results demonstrate synergism between curcumin and 5-FU at higher doses against the human colon cancer cell line HT-29. This synergism was associated with the decreased expression of COX-2 protein.

Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer

“…This study establishes, for the first time, the comparable or greater growthinhibitory and apoptotic effects of liposomal curcumin with oxaliplatin, with virtually no side effects for the former, at least in animals. Interestingly, a previous study showed synergism between curcumin and 5-fluorouracil against human colon cancer cells in vitro, associated with a 6-fold reduction of cyclooxygenase-2 protein expression (23). In our study, in vitro synergism was seen between liposomal curcumin and oxaliplatin at a 4:1 ratio, but there was no substantial synergy in vivo.…”

The combination of baicalin and baicalein enhances apoptosis via the ERK/p38 MAPK pathway in human breast cancer cells

“…In one study, curcumin was tested for its ability to compromise the proapoptotic activity of camptothecin, alkylating agents and anthracyclines [47] . In other studies, curcumin instead showed synergistic growth inhibition and stimulated apoptosis in some cancer cells when combined with chemotherapeutic drugs such as bortezomib and 5-fluorouracil [48] . Therefore, the combined effect of the substances likely depends on drug-drug interactions.…”

The Potential Role of Curcumin for Treatment of Pancreatic Cancer

“…Other mechanisms involved in the anticancer effects of curcumin include the downregulation of Akt, cyclooxygenase-2 (COX2), prostaglandin E2 or signal transducers and activators of transcription 3 (STAT3) (Aggarwal & Shishodia, 2006), which prevents cancer cells from escaping through alternative signaling pathways. Curcumin can also potentiate the anticancer effects of cytotoxic agents such as cisplatin, 5-fluorouracil and gemcitabine (Du et al, 2006;Kunnumakkara et al, 2007;Tsai et al, 2011).…”