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. 2009;61(4):544-53.
doi: 10.1080/01635580902752262.

Curcumin synergizes with resveratrol to inhibit colon cancer

Adhip P N Majumdar  1 , Sanjeev Banerjee, Jyoti Nautiyal, Bhaumik B Patel, Vaishali Patel, Jianhua Du, Yingjie Yu, Althea A Elliott, Edi Levi, Fazlul H Sarkar
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Curcumin synergizes with resveratrol to inhibit colon cancer (VSports注册入口)

Adhip P N Majumdar et al. Nutr Cancer. 2009.

Abstract (VSports手机版)

Development and progression of many malignancies, including colorectal cancer, are associated with activation of multiple signaling pathways VSports手机版. Therefore, inhibition of these signaling pathways with noncytotoxic natural products represents a logical preventive and/or therapeutic approach for colon cancer. Curcumin and resveratrol, both of which inhibit the growth of transformed cells and colon carcinogenesis, were selected to examine whether combining them would be an effective preventive and/or therapeutic strategy for colon cancer. Indeed, the combination of curcumin and resveratrol was found to be more effective in inhibiting growth of p53-positive (wt) and p53-negative colon cancer HCT-116 cells in vitro and in vivo in SCID xenografts of colon cancer HCT-116 (wt) cells than either agent alone. Analysis by Calcusyn software showed synergism between curcumin and resveratrol. The inhibition of tumors in response to curcumin and/or resveratrol was associated with the reduction in proliferation and stimulation of apoptosis accompanied by attenuation of NF-kappaB activity. In vitro studies have further demonstrated that the combinatorial treatment caused a greater inhibition of constitutive activation of EGFR and its family members as well as IGF-1R. Our current data suggest that the combination of curcumin and resveratrol could be an effective preventive/therapeutic strategy for colon cancer. .

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VSports在线直播 - Figures

FIG. 1.
FIG. 1.
A: Typical dose-response curves produced by fixed-ratio method. Fraction of HCT-116 (wt) cells affected by different combination of curcumin and resveratrol (fixed ratio) is higher than either agent alone. Fa represents the fraction of cells that is growth inhibited in response to curcumin and/or resveratrol. This is calculated as 1 – fraction of surviving cells. Fa values for each treatment were utilized to conduct synergy analysis by Calcusyn software as described in Methods and Materials. B: The isobole for ED75, as analyzed using the Calcusyn software, shows that the combination of curcumin and resveratrol is below the line of additivity indicating synergism.
FIG. 2.
FIG. 2.
A: The combination of curcumin and resveratrol causes greater inhibition of growth of colon cancer p53 positive (wild type) and the p53-negative (p53−/−) HCT-116 cells and B: also stimulates apoptosis of HCT-116 (wt) cells than either agent alone. Each value represents mean ±SEM of 4 to 6 observations. *P < 0.025 or lower compared to control. Cur, curcumin; Resv, resveratrol.
FIG. 3.
FIG. 3.
The levels of nonphosphorylated (total) and tyrosine phosphorylated forms of EGFR, HER-2, HER-3, IGF-1R, is lower in HCT-116 (wt) cells following 48-h incubation in the presence of curcumin (10 μM), resveratrol (10 μM), or a combination of both. Cur, curcumin; Resv, resveratrol.
FIG. 4.
FIG. 4.
Increases in A: IGFBP-3 expression and B: sequestration of IGF-1 by IGFBP-3 in HCT-116 (wt) in response to curcumin, resveratrol, or curcumin and resveratrol. IGFBP-3 was immunoprecipitated from cell lysates with anti-IGFBP-3 antibodies, and the immunoprecipitates were subjected to Western blot analysis for IGF-1. The numbers underneath each band represent percent of representative control. The experiment was repeated at least 3 times. Cur, curcumin; Res and Resv, resveratrol.
FIG. 5.
FIG. 5.
Curcumin in combination with resveratrol causes A: a greater inhibition of HCT-116 (wt) colon cancer xenograft growth in SCID mice, B: is associated with decreased proliferation (mitotic index), C: increased apoptosis [TUNEL assay], and D: decreased NF-κB DNA binding activity. *P < 0.01 compared to control. Data in panel (A) for control and curcumin are similar to those recently published by our laboratory (39).
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