The synergystic effects of omega-3 fatty acids against 5-fluorouracil-induced mucosal impairment in mice

Sebe, Mayu; Tsutsumi, Rie; Yamaguchi, Sotaro; Horikawa, Yousuke T.; Harada, Nagakatsu; Oyama, Takuro; Kakuta, Nami; Tanaka, Katsuya; Tsutsumi, Yasuo M.; Nakaya, Yutaka; Sakaue, Hiroshi

doi:10.1186/s40795-016-0057-7

Cited by 7 publications

(8 citation statements)

References 38 publications

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“…The combined strategy not only decreased the tumor burden but also significantly reduced the associated side effects. 6,29 Various mechanisms have been hypothesized to explain the modulation of the tumor cell response to chemotherapeutic drugs by FO which includes an alteration in the expression of pro-apoptotic proteins and membrane characteristics by incorporation of n-3 PUFAs in the membrane. However, no experimental data to validate this hypothesis are available till date, which necessitates further investigation.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis mediated chemosensitization of tumor cells to 5-fluorouracil on supplementation of fish oil in experimental colon carcinoma

et al. 2017

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5-Fluorouracil has been considered as a cornerstone therapy for colorectal cancer; however, it suffers from low therapeutic response rate and severe side effects. Therefore, there is an urgent need to increase the clinical efficacy of 5-fluorouracil. Recently, fish oil rich in n-3 polyunsaturated fatty acids has been reported to chemosensitize tumor cells to anti-cancer drugs. This study is designed to understand the underlying mechanisms of synergistic effect of fish oil and 5-fluorouracil by evaluation of tumor cell-associated markers such as apoptosis and DNA damage. The colon cancer was developed by administration of N,N-dimethylhydrazine dihydrochloride and dextran sulfate sodium salt. Further these animals were treated with 5-fluorouracil, fish oil, or a combination of both. In carcinogen-treated animals, a decrease in DNA damage and apoptotic index was observed. There was also a decrease in the expression of Fas, FasL, caspase 8, and Bax, and an increase in Bcl-2. In contrast, administration of 5-fluorouracil and fish oil as an adjuvant increased both DNA damage and apoptotic index by activation of both extrinsic and intrinsic apoptotic pathways as compared to the other groups. The increased pro-apoptotic effect by synergism of 5-fluorouracil and fish oil may be attributed to the incorporation of n-3 polyunsaturated fatty acids in membrane, which alters membrane fluidity in cancer cells. In conclusion, this study highlights that the induction of apoptotic pathway by fish oil may increase the susceptibility of tumors to chemotherapeutic regimens.

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Section: Discussionmentioning

confidence: 99%

Apoptosis mediated chemosensitization of tumor cells to 5-fluorouracil on supplementation of fish oil in experimental colon carcinoma

et al. 2017

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“…Several in vivo studies have described that PUFAs can reduce 5-FU-related toxicity and potentiate 5-FU anti-cancer activity though the reduction of tumor burden and DNA damage and the increase of apoptosis [131][132][133]. A recently study in rat models showed that combining PUFAs with 5-FU and irinotecan could help restore lipid stocks, thus potentially limiting 5-FU-associated side effects [134].…”

Section: Diets Rich In Polyunsaturated Fatty Acidsmentioning

confidence: 99%

The Role of the Gut Microbiome in Colorectal Cancer Development and Therapy Response

Sánchez-Alcoholado

Ramos‐Molina

Otero

et al. 2020

Cancers

237

139

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Colorectal cancer (CRC) is the third most common cancer worldwide and the leading cause of cancer-related deaths. Recently, several studies have demonstrated that gut microbiota can alter CRC susceptibility and progression by modulating mechanisms such as inflammation and DNA damage, and by producing metabolites involved in tumor progression or suppression. Dysbiosis of gut microbiota has been observed in patients with CRC, with a decrease in commensal bacterial species (butyrate-producing bacteria) and an enrichment of detrimental bacterial populations (pro-inflammatory opportunistic pathogens). CRC is characterized by altered production of bacterial metabolites directly involved in cancer metabolism including short-chain fatty acids and polyamines. Emerging evidence suggests that diet has an important impact on the risk of CRC development. The intake of high-fiber diets and the supplementation of diet with polyunsaturated fatty acids, polyphenols and probiotics, which are known to regulate gut microbiota, could be not only a potential mechanism for the reduction of CRC risk in a primary prevention setting, but may also be important to enhance the response to cancer therapy when used as adjuvant to conventional treatment for CRC. Therefore, a personalized modulation of the pattern of gut microbiome by diet may be a promising approach to prevent the development and progression of CRC and to improve the efficacy of antitumoral therapy.

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“…Vasudevan et al demonstrated a synergistic anti-cancer effect between EPA and a regimen of 5-fluorouracil (5-FU) and oxaliplatin in vitro and in vivo against HT29 and HCT116 CRC models [ 52 ]. Several other in vivo studies have demonstrated that O3FAs can both potentiate 5-FU anti-cancer activity (reduction of tumour burden, increased apoptosis, and DNA damage) and also reduce 5-FU-related toxicity [ 53 – 55 ]. In 2017, a study showed that 5-FU and irinotecan treatment can lead to impaired lipid storage in rat models, resulting in loss of O3FA in tissues.…”

Section: Preclinical Data Supporting the Anti-crc Activity Of O3fasmentioning

confidence: 99%

Omega-3 polyunsaturated fatty acids as adjuvant therapy of colorectal cancer

Volpato

Hull

2018

Cancer Metastasis Rev

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The majority of evidence linking anti-colorectal cancer (CRC) activity with omega-3 polyunsaturated fatty acids (O3FAs) has focussed on decreased CRC risk (prevention). More recently, preclinical data and human observational studies have begun to make the case for adjuvant treatment of advanced CRC. Herein, we review latest data regarding the effect of O3FAs on post-diagnosis CRC outcomes, including mechanistic preclinical data, evidence that O3FAs have beneficial effects on efficacy and tolerability of CRC chemotherapy, and human epidemiological data linking dietary O3FA intake with CRC outcomes. We also highlight ongoing randomised controlled trials of O3FAs with CRC endpoints and discuss critical gaps in the evidence base, which include limited understanding of the effects of O3FAs on the tumour microenvironment, the host immune response to CRC, and the intestinal microbiome.

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The synergystic effects of omega-3 fatty acids against 5-fluorouracil-induced mucosal impairment in mice

Cited by 7 publications

References 38 publications

Apoptosis mediated chemosensitization of tumor cells to 5-fluorouracil on supplementation of fish oil in experimental colon carcinoma

Apoptosis mediated chemosensitization of tumor cells to 5-fluorouracil on supplementation of fish oil in experimental colon carcinoma

The Role of the Gut Microbiome in Colorectal Cancer Development and Therapy Response

Omega-3 polyunsaturated fatty acids as adjuvant therapy of colorectal cancer

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