Oxyphytosterols as Active Ingredients in Wheat Bran Suppress Human Colon Cancer Cell Growth: Identification, Chemical Synthesis and Biological Evaluation, J Agric Food Chem. 2015 Feb 6, Zhu Y, Soroka D, Sang S.
NC A&T University
Consumption of whole grains has been reported to be associated with a lower risk of several lifestyle-related diseases such as colorectal cancer, type 2 diabetes and cardiovascular disease (CVD). Recent studies illustrated that phytochemicals in wheat bran (WB) may protect against colorectalcancer. There is a growing interest in the phytosterol contents of foods as either intrinsic or added components due to their outstanding physiological properties, such as cholesterol-lowering effects and antiproliferative properties. However, little is known whether phytosterols in WB contribute to the observed chemopreventative activity of the grain. In the present study, we directly purified and identified four oxyphytosterols 1-4 from sterol-enriched fraction of WB, and also successfully synthesized five sterol oxides 5-8 and 13. Using these nine compounds as references, we outlined a comprehensive profile of steroids in WB using HPLC-ESI/MSn (n = 2-3) techniques for the first time. Among them, three sterol oxides 13, 14 and 18 are novel compounds, and fourteen compounds 3, 4, 6-11, 13, 14, 16 and 18-20 were reported in WB for the first time. It is also the first report of the complete NMR data of two unusual 3-ketophytosterols 1 and 2. MTT assays on available sterol oxides 1-8 and 13 showed that seven sterol oxides 2-8 exerted significant antiproliferative effects, with oxysterol 8 being the most active one in both HCT-116 and HT-29 human colon cancer cells. ELISA assays further demonstrated that the four most active sterol oxides 5-8 could induce cell death through the apoptosis pathway. Study on structure-activity relationship (SAR) of sterol oxides against the growth of human colon cancer cells revealed (1) an entity of 3-ol-5-en-7-one in the structure is more favorable for anti-cancer activity than a partial structure of 6-ol-4-en-3-one; (2) an entity of 5-en-3,7-diol in the structure greatly increases the activity compared to 3-ol-5-en-7-one; (3) a free hydroxyl group at C-3β in an entity of 3-ol-5-en-7-one or 5-en-3,7-diol plays a crucial role in the observed activity; and (4) a lipophilic side chain of eight carbons in length yields the optimal activities. Our results showed that phytosterols, particularly oxyphytosterols, in WB possess significant antiproliferative properties, and thereby may greatly contribute to the observed chemoprevention of whole grain wheat.
- [PubMed – as supplied by publisher]