Journal
MOLECULAR MEDICINE REPORTS
Volume 14, Issue 1, Pages 491-498Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2016.5285
Keywords
Mahonia bealei; palmatine; inflammation; cytokine; small intestine; colon; colorectal cancer; Apc(Min/+) mice
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Funding
- Natural Science Foundation of Jiangsu Province (China) [BK20131309]
- NIH/NCCAM [AT 004418, AT005362]
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Mahonia bealei is a Chinese folk medicine used to treat various ailments, in particular gastrointestinal inflammation-related illnesses, and palmatine is one of its active constituents. In this study, Apc(Min/+) mice, a genetically engineered model, were used to investigate the effects of palmatine on the initiation and progression of gut inflammation and tumorigenesis enhanced by a high-fat diet. The in vitro antiproliferation and anti-inflammation effects of palmatine were evaluated on HT-29 and SW-480 human colorectal cancer cell lines. The concentration-related antiproliferative effects of palmatine on both cell lines (P<0.01) were observed. Palmatine significantly inhibited lipopolysaccharide-induced increase in cytokine interleukin (IL)-8 levels in the HT-29 cells (P<0.01). In the in vivo studies with Apc(Min/+) mice, after 10 or 20 mg/kg/day oral palmatine treatment, tumor numbers were significantly reduced in the small intestine and colon in a dose-dependent manner (P<0.01 compared with the model group). The results were supported by tumor distribution data, body weight changes and organ index. The effect on survival was also dose-dependent. Both the low-and high-dose palmatine treatments significantly increased the life span of the mice (P<0.01). The gut histology from the model group showed a prominent adenomatous change along with inflammatory lesions. With palmatine treatment, however, the dysplastic changes were greatly reduced in the small intestine and colon tissue. Reverse transcription-quantitative polymerase chain reaction analysis of interleukin (IL)-1 alpha, IL1-beta, IL-8, granulocyte-colony stimulating factor and granulocyte macrophage colony-stimulating factor in the gut tissue showed that these inflammatory cytokines were reduced significantly following treatment (all P<0.01); serum cytokine levels were also decreased. Data suggests that palmatine has a clinical value in colorectal cancer therapeutics, and this action is likely linked to the inhibition of inflammatory cytokines.
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