Effects of propolis and gamma-cyclodextrin on intestinal neoplasia in normal weight and obese mice

Abstract

Obesity is associated with colorectal cancer (CRC). This effect might be attributed to adipokine-supported signaling. We have established that propolis suppresses survival signaling in CRC cells in vitro; therefore, we ascertained the ability of a propolis supplement to modulate intestinal neoplastic development in C57BL/6J-ApcMin/+/J mice in the lean and obese state. To induce obesity, mice were fed with a Western diet containing 40% fat. Since the propolis supplement includes gamma-cyclodextrin, the interventions included diets supplemented with or without gamma-cyclodextrin. The animals were administered the following diets: (1) control diet, (2) control diet/gamma-cyclodextrin, (3) control diet/propolis, (4) Western diet, (5) Western diet/gamma-cyclodextrin, and (6) Western diet/propolis. Western diet, resulting in obesity, accelerated neoplastic progression, as evidenced by the larger size and higher grade dysplasia of the neoplasms. In the context of normal weight, gamma-cyclodextrin and propolis affected neoplastic progression, as determined by the size of the lesions and their grade of dysplasia. A statistically significant decrease in the number of adenomas was detected in mice fed a control diet with the propolis supplement (61.8 ± 10.6 vs. 35.3 ± 7.6, P = 0.008). Although there was no significant difference in the polyp numbers between the six groups, the mice with the lowest number and size of adenomas were those fed a Western diet with gamma-cyclodextrin. This unexpected outcome might be explained by the increased levels of apoptosis detected in the intestinal tissues of these obese mice. We posit that butyrate derived from the metabolism of gamma-cyclodextrin may contribute to the decreased neoplastic burden in the context of obesity; however, future studies are required to address this possibility.

Our in vivo analyses revealed that a propolis supplement significantly inhibits the intestinal neoplastic burden in the context of normal weight, but not obesity. In contrast, gamma-cyclodextrin, a food additive with which propolis is formulated, suppresses in a statistically significant manner the intestinal neoplastic burden in the context of obesity. We have also established that early-stage neoplasms in obese mice exhibit a lower number of somatic mutations than these in normal weight mice.

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