A novel compound, ferulic acid-bound resveratrol, induces the tumor suppressor gene p15 and inhibits the three-dimensional proliferation of colorectal cancer cells
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Resveratrol, a phytoalexin present in grapes and other edible foods, has been reported to have beneficial effects against various diseases including cancer. We previously reported that resveratrol and its derivative, caffeic acid-adducted resveratrol, selectively inhibit the three-dimensional (3D) proliferation of a human colorectal cancer cell line, HCT116 with activating KRAS mutation. Herein, we demonstrated that a novel compound, ferulic acid-bound resveratrol, also represses the 3D proliferation of HCT116 cells. We observed that resveratrol conjugated to two ferulic acids represses the 3D proliferation of HCT116 cells more strongly than resveratrol and resveratrol conjugated to one ferulic acid. Resveratrol conjugated to two ferulic acids also inhibited the 3D proliferation of MCF7 human breast cancer cells. We further uncovered that the resveratrol derivative increases the mRNA level of the tumor suppressor p15, a CDK inhibitor that functions as a brake of cell proliferation in HCT116 cells. These results imply that the resveratrol derivative represses 3D proliferation via increasing p15 expression in HCT116 cells.
KeywordsResveratrol derivative Three-dimensional proliferation CDK inhibitor p15 Colorectal cancer
We thank Keishi Tamura and Haruna Okamoto for their helpful discussions and technical assistance. This work was supported by JSPS KAKENHI Grant Number 17K07184 (to YK) and the Naito Foundation (to YK). We thank Joe Barber Jr., PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
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Conflict of interest
The resveratrol derivatives (UHA023, UHA024, and UHA025) used in this study were provided by UHA Mikakuto Co., Ltd. Taiji Matsukawa and Satoshi Doi are employees of UHA Mikakuto Co., Ltd. The authors have no conflict of interest to declare.
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