Effect of fisetin supplementation on inflammatory factors and matrix metalloproteinase enzymes in colorectal cancer patients

Abstract

A growing body of evidence indicates that inflammation is associated with tumorigenesis, metastasis and chemotherapeutic resistance in patients with colorectal cancer (CRC). Natural flavonoids are promising agents for inflammation-related tumor progression in patients with CRC. This study aimed to assess the efficacy of flavonoid fisetin supplementation on the inflammatory status and matrix metalloproteinase (MMP) levels in these patients. In this double-blind, randomized placebo-controlled clinical trial, 37 CRC patients undergoing chemotherapy were assigned to receive either 100 mg fisetin (n = 18) or placebo (n = 19) for seven consecutive weeks. The supplementation began one week before chemotherapy and continued until the end of the second chemotherapy cycle. Levels of interleukin (IL)-8, IL-10, high-sensitivity C-reactive protein (hs-CRP), MMP-7, and MMP-9 were measured in plasma using ELISA, before and after the intervention. The trial was registered at http://www.irct.ir (code: IRCT2015110511288N9). The participants were 55.59 ± 15.46 years old with 62.16% being male. After the intervention, the plasma levels of IL-8 and hs-CRP reduced significantly in the fisetin group (p < 0.04 and p < 0.01, respectively). Additionally, fisetin supplementation suppressed the values of MMP-7 levels (p < 0.02). However, significant changes were observed only in IL-8 concentrations in the fisetin group when compared with the placebo group (p < 0.03). The changes in the levels of other metabolic factors were not statistically significant. According to the results, fisetin could improve the inflammatory status in CRC patients, suggesting it as a novel complementary antitumor agent for these patients and warranting further studies.

Attenuation of reserpine‑induced fibromyalgia via ROS and serotonergic pathway modulation by fisetin, a plant flavonoid polyphenol

“…In the past few decades, medicines of herbal origin, including Rhizoma drynariae (75) and Baishao zongdai (68), demonstrated significant efficacy in terms of safety in the management of FM. Fisetin, a flavonoid polyphenol phytoconstituent, also showed promising potential for the clinical management of colorectal cancer (76). A few human clinical studies have been performed using fisetin as a dietary supplement for the management of various disorders, including frailty syndrome, mild cognitive impairment, diabetic nephropathy and Gulf War Syndrome (77).…”

Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies

“…To put this into context, the average daily consumption of Fisetin is thought to be 0.4 mg per day [ 109 ]. In terms of clinical trials, this 100 mg dose has been used in a colorectal cancer chemotherapy study and has been shown to reduce inflammatory markers, although numbers were small and no clinical cancer end points were assessed [ 121 ]. There were no safety issues at this dose and the research team felt there was potential for further studies to investigate its adjuvant value.…”

Flavonoids in Cancer Metastasis

“…Inflammation promotes carcinogenesis, metastasis and therapeutic resistance of colorectal cancer [ 119 , 120 , 121 ]. Therefore, a double-blinded, randomized placebo-controlled trial evaluated effects of supplementation with fisetin on inflammatory status and MMPs level in 37 CRC patients.…”

“…The fisetin supplementation, which began a week before chemotherapy and was continuous until the end of the second chemotherapy cycle, decreased plasma levels of IL-8, high sensitivity C-reactive protein (hs-CRP) as well as MMP-7 level. The efficacy of fisetin in the improvement of inflammatory status of colorectal carcinoma patients can be associated with its role of a complementary antitumor agent [ 119 ]. The effectiveness of chemotherapy in colorectal cancer patients evaluated as combined with the herbal agent MB-6 composed of fermented soybean extract, green tea extract, Antrodia camphorata mycelia, spirulina, grape seed extract, and curcumin extract.…”