Combined Curcumin and Luteolin Synergistically Inhibit Colon Cancer via Regulating Notch1 and TGF-β Signaling Pathways in Cells and Xenograft Mice

Rukayat Aromokeye, Tennessee State University


Colon cancer is the second major reason of all carcinoma-related mortalities worldwide and third in the United States. Current colon cancer treatments, including surgery, chemotherapy and radiotherapy, have adverse effects and significantly decrease patients' quality of life. Developing treatments without side effects is critical in helping American colon cancer patients have a healthy life. Phytochemicals are non-nutritious compounds present in plants, exert an anti-colon cancer effect with low side effects. However, the required dosages to exert anti-colon cancer effects of the phytochemicals are too high to be achieved by dietary intake.This study aimed to select a combination of luteolin and curcumin at the lowest concentrations/dosages with the highest inhibitory effect on colon cancer development and to investigate potential molecular mechanisms of this anti-colon cancer effect by the combination in human-colon-cancer-cells and xenograft-mice. Through pairwise combination screens, we identified that the combination of luteolin (LUT) at 30μM and curcumin (CUR) at 15μM (C15L30) synergistically suppressed proliferation in colon cancer CL-188 cells, while the individual chemicals had a little inhibitory effect at the selected concentrations. This result was also confirmed in another colon cancer DLD-1 cells, suggesting that this synergistic inhibitory effect of C15L30 applies to different colon cancers. The combination C15L30 synergistically suppressed the closure of the wound in CL-188 cells by wound healing assay. We also found that the combination of CUR and LUT (at 20mg/kg/day and 10mg/kg/day respectively, IP injection, 5 days for 2 weeks) synergistically suppressed tumor growth in CL-188 cells-derived xenograft mice. Western blot showed that protein levels of Notch1 and TGF-β were synergistically reduced by the combination, both in CL-188 cell and xenograft tumors. H&E stain of the tumor revealed that necrosis was synergistically increased with the combined CUR and LUT, but the individual treatment with CUR and LUT had little significant repercussions on tumor necrosis. These outcomes show that combined luteolin and curcumin synergistically inhibit colon cancer by suppressing cell proliferation, necrosis, and migration via regulating Notch1 and TGF-β pathways.This study provides solid evidence that colon cancer may be treated by consuming foods rich in luteolin and curcumin, although more studies are needed.

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Recommended Citation

Rukayat Aromokeye, "Combined Curcumin and Luteolin Synergistically Inhibit Colon Cancer via Regulating Notch1 and TGF-β Signaling Pathways in Cells and Xenograft Mice" (2021). ETD Collection for Tennessee State University. Paper AAI28715925.