cytellin and Colorectal-Neoplasms

Phytosterols are widely present in vegetable oils, nuts, cereal products, fruits, and berries. Phytosterol-induced treatment sensitivity has recently shed light on alleviating multidrug resistance in cancer therapy. Here, we demonstrated that β-sitosterol, the most common dietary phytosterol, recovers oxaliplatin (OXA) sensitivity in drug-resistant colorectal cancer (CRC) cells by inhibiting breast cancer resistance protein (BCRP) expression. We further showed evidence that β-sitosterol could activate p53 by disrupting the p53-MDM2 interaction, leading to an increase in p53 translocation to the nucleus and silencing the nuclear factor-κB (NF-κB) pathway, which is necessary for BCRP expression. Finally, we suggested that the combination of OXA and β-sitosterol has a synergistic tumor suppression effect in vivo using a xenograft mouse model. These results revealed that β-sitosterol is able to mediate the p53/NF-κB/BCRP signaling axis to regulate the response of CRC to chemotherapy. The combined application of β-sitosterol and OXA can be a potential way to improve CRC treatment.

Topics: Animals; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily G, Member 2; Colorectal Neoplasms; Down-Regulation; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; HCT116 Cells; Humans; Mice, Inbred BALB C; Neoplasm Proteins; Oxaliplatin; Protein Interaction Maps; Proto-Oncogene Proteins c-mdm2; Sitosterols; Tumor Suppressor Protein p53

Topics: Adenocarcinoma; Animals; Apoptosis; Cell Line, Tumor; Colorectal Neoplasms; Fatty Acids, Volatile; Gastrointestinal Microbiome; HCT116 Cells; HT29 Cells; Humans; Lipid Metabolism; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Sitosterols; Xenograft Model Antitumor Assays

A study in rodent models showed that phytosterols protected against colon carcinogenesis, probably by inhibiting dysregulated cell cycle progression and inducing cellular apoptosis. However, epidemiological studies on the relationship between phytosterols and colorectal cancer risk are quite limited. The aim of this study was to investigate dietary phytosterol intake in relation to colorectal cancer risk in the Chinese population. A case-control study was conducted from July 2010 to June 2016, recruiting 1802 eligible colorectal cancer cases plus 1813 age (5-year interval) and sex frequency-matched controls. Dietary information was collected by using a validated FFQ. The OR and 95 % CI of colorectal cancer risk were assessed by multivariable logistic regression models. A higher total intake of phytosterols was found to be associated with a 50 % reduction in colorectal cancer risk. After adjusting for various confounders, the OR of the highest quartile intake compared with the lowest quartile intake was 0·50 (95 % CI 0·41, 0·61, P trend<0·01) for total phytosterols. An inverse association was also found between the consumption of β-sitosterol, campesterol, campestanol and colorectal cancer risk. However, stigmasterol intake was related to an increased risk of colorectal cancer. No statistically significant association was found between β-sitostanol and colorectal cancer risk. Stratified analysis by sex showed that the positive association of stigmasterol intake with colorectal cancer risk was found only in women. These data indicated that the consumption of total phytosterols, β-sitosterol, campesterol and campestanol is inversely associated with colorectal cancer risk in a Chinese population.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; China; Colorectal Neoplasms; Diet; Energy Intake; Feeding Behavior; Female; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Phytosterols; Plant Extracts; Risk; Sex Factors; Sitosterols

Plant sterols in vegetable foods might prevent colorectal cancer.. The objective was to study plant sterol intakes in relation to colorectal cancer risk in an epidemiologic study.. The study was performed within the framework of the Netherlands Cohort Study on Diet and Cancer in 120852 subjects who completed a baseline questionnaire in 1986. After 6.3 y of follow-up, 620 colon and 344 rectal cancer cases were detected. A case-cohort approach was used to calculate confounder-adjusted rate ratios (RRs) and their 95% CIs for quintiles of plant sterol intake.. The total mean (+/-SD) intake of campesterol, stigmasterol, beta-sitosterol, campestanol, and beta-sitostanol was 285 +/- 97 mg/d. Major contributors to plant sterol intake were bread (38%), vegetable fats (26%), and fruit and vegetables (21%). For men, there was no clear association between intake of any of the plant sterols and colon cancer risk when age, smoking, alcohol use, family history of colorectal cancer, education level, and cholecystectomy were controlled for. Adjustment for energy did not alter the result. For rectal cancer, adjustment for energy resulted in positive associations between risk and campesterol and stigmasterol intakes. For women, there was no clear association between intake of any of the plant sterols and colorectal cancer risk.. A high dietary intake of plant sterols was not associated with a lower risk of colon and rectal cancers in the Netherlands Cohort Study on Diet and Cancer.

Topics: Aged; Bread; Case-Control Studies; Cholesterol; Cohort Studies; Colorectal Neoplasms; Confounding Factors, Epidemiologic; Dietary Fats; Female; Follow-Up Studies; Fruit; Humans; Hypolipidemic Agents; Male; Middle Aged; Netherlands; Phytosterols; Prospective Studies; Rectal Neoplasms; Risk Factors; Sitosterols; Stigmasterol; Surveys and Questionnaires; Vegetables