Archive

Research Area: Cancer

Metabolic influence of walnut phenolic extract on mitochondria in a colon cancer stem cell model.

Choi, J., P.K. Shin, Y. Kim, C.P. Hong, S.W. Choi, 2019. Metabolic influence of walnut phenolic extract on mitochondria in a colon cancer stem cell model. Eur J Nutr. 58(4):1635-1645.

Purpose: Walnut phenolic extract (WPE) reduces proliferation and enhances differentiation of colon cancer stem cells (CSCs). The present study investigated the metabolic influence of WPE on the mitochondrial function of colon CSCs to determine its underlying mechanism. Methods: CD133+CD44+ HCT116 colon cancer cells were selected by fluorescence-activated cell sorting and were treated with or without 40 µg/mL WPE. RNA-sequencing (RNA-Seq) was performed to identify differentially expressed genes (DEGs), which were further validated with RT-PCR. WPE-induced alterations in mitochondrial function were investigated through a mitochondrial stress test by determining cellular oxygen consumption rate (OCR), an indicator of mitochondrial respiration, and extracellular acidification rate (ECAR), an indicator of glycolysis, which were further confirmed by glucose uptake and lactate production tests. Results: RNA-Seq analysis identified two major functional clusters: metabolic and mitochondrial clusters. WPE treatment shifted the metabolic profile of cells towards the glycolysis pathway (ΔECAR = 36.98 mpH/min/ptn, p = 0.02) and oxidative pathway (ΔOCR = 29.18 pmol/min/ptn, p = 0.00001). Serial mitochondrial stimulations using respiration modulators, oligomycin, carbonyl cyanide-4 (trifluoromethoxy) phenylhydrazone, and rotenone/antimycin A, found an increased potential of mitochondrial respiration (ΔOCR = 111.5 pmol/min/ptn, p = 0.0006). WPE treatment also increased glucose uptake (Δ = 0.39 pmol/µL, p = 0.002) and lactate production (Δ = 0.08 nmol/µL, p = 0.005). Conclusions: WPE treatment shifts the mitochondrial metabolism of colon CSC towards more aerobic glycolysis, which might be associated with the alterations in the characteristics of colon CSC.

Nut and peanut butter consumption and the risk of lung cancer and its subtypes: A prospective cohort study.

Nieuwenhuis, I., P.A. van den Brandt, 2019. Nut and peanut butter consumption and the risk of lung cancer and its subtypes: A prospective cohort study. Lung Cancer. 128:57-66.
Objectives: Nut consumption has been associated with reduced cancer-related mortality, but evidence for a relation between nut intake and lung cancer risk is limited. We investigated the association between total nut, tree nut, peanut, and peanut butter intake and the risk of lung cancer and its subtypes in the Netherlands Cohort Study. Materials and Methods: In 1986, dietary and lifestyle habits of 120,852 participants, aged 55–69 years, were measured with a questionnaire. After 20.3 years of follow-up, 3720 subcohort members and 2861 lung cancer cases were included in multivariable case-cohort analyses. Results: Total nut intake was not significantly associated with total lung cancer risk in men or women. For small cell carcinoma, a significant inverse association with total nut intake was observed in men after controlling for detailed smoking habits (HR (95%CI) for 10+ g/day vs. non-consumers: 0.62 (0.43-0.89), p-trend: 0.024). Inverse relations with small cell carcinoma were also found for tree nut and peanut intake in men in continuous analyses (HR (95%CI) per 5g/day increment: 0.70 (0.53-0.93) and 0.93 (0.88-0.98), respectively). For the other lung cancer subtypes, no significant associations were seen in men. Nut intake was not related to the risk of lung cancer subtypes in women, and no associations were found for peanut butter in both sexes. Conclusion: Increased nut intake might contribute to the prevention of small cell carcinoma in men. No significant associations were found in men for the other subtypes or total lung cancer, in women, or for peanut butter intake.

Nut Consumption and Survival in Patients With Stage III Colon Cancer: Results From CALGB 89803 (Alliance).

Fadelu, T., S. Zhang, D. Niedzwiecki, X. Ye, L.B. Saltz, R.J. Mayer, R.B. Mowat, R. Whittom, A. Hantel, A.B. Benson, D.M. Atienza, M. Messino, H.L. Kindler, A. Venook, S. Ogino, K. Ng, K. Wu, W. Willett, E. Giovannucci, J. Meyerhardt, Y. Bao, C.S. Fuchs, 2018. Nut Consumption and Survival in Patients With Stage III Colon Cancer: Results From CALGB 89803 (Alliance). J Clin Oncol. 36(11):1112-1120.

Purpose: Observational studies have reported increased colon cancer recurrence and mortality in patients with states of hyperinsulinemia, including type 2 diabetes, obesity, sedentary lifestyle, and high glycemic load diet. Nut intake has been associated with a lower risk of type 2 diabetes, metabolic syndrome, and insulin resistance. However, the effect of nut intake on colon cancer recurrence and survival is not known. Patients and Methods: We conducted a prospective, observational study of 826 eligible patients with stage III colon cancer who reported dietary intake on food frequency questionnaires while enrolled onto a randomized adjuvant chemotherapy trial. Using Cox proportional hazards regression, we assessed associations of nut intake with cancer recurrence and mortality. Results: After a median follow-up of 6.5 years, compared with patients who abstained from nuts, individuals who consumed two or more servings of nuts per week experienced an adjusted hazard ratio (HR) for disease-free survival of 0.58 (95% CI, 0.37 to 0.92; Ptrend = .03) and an HR for overall survival of 0.43 (95% CI, 0.25 to 0.74; Ptrend = .01). In subgroup analysis, the apparent benefit was confined to tree nut intake (HR for disease-free survival, 0.54; 95% CI, 0.34 to 0.85; Ptrend = .04; and HR for overall survival, 0.47; 95% CI, 0.27 to 0.82; Ptrend = .04). The association of total nut intake with improved outcomes was maintained across other known or suspected risk factors for cancer recurrence and mortality. Conclusion: Diets with a higher consumption of nuts may be associated with a significantly reduced incidence of cancer recurrence and death in patients with stage III colon cancer.

Role of omega-3 polyunsaturated fatty acids in preventing gastrointestinal cancers: current status and future perspectives.

Lee, H.J., Y.M. Han, J.M. An, E.A. Kang, Y.J. Park, J.Y. Cha, K.B. Hahm, 2018. Role of omega-3 polyunsaturated fatty acids in preventing gastrointestinal cancers: current status and future perspectives. Expert Rev Anticancer Ther. 17:1-15.

Although inflammation is defensive and healing process that maintains organ homeostasis, unresolved inflammation can lead to diseases. Polyunsaturated fatty acids (PUFAs), especially n-6 PUFAs abundant in Western diet, are precursors of pro-inflammatory mediators, whereas n-3 PUFAs possess anti-inflammatory properties. Therefore, interest in the cancer-preventive effect of n-3 PUFAs is increasing. Areas covered: We have observed significant reductions of gastrointestinal tumorigenesis in the Fat-1 transgenic mouse as evidenced that the decrease in Helicobacter pylori-infected gastric tumorigenesis, colon, biliary, and pancreatic cancer was seen in Fat-1 mice producing n-3 PUFAs. However, despite many studies showing benefits, evidence-based medicine regarding molecular pathology, epidemiology, and clinical achievement of cancer prevention of n-3 PUFAs are still limited. Expert commentary: Primary deficiency of eicosapentaenoic acids and docosahexaenoic acids in Western diets can explain the risk of cancer development and the importance of n-3/n-6 PUFA ratio in reducing cancer risk. Alteration of cell membrane composition during carcinogenesis is particularly important, due to increased rate of lipid/cholesterol synthesis in cancerous tissues. Here, we discuss that direct incorporation of n-3 PUFAs in the cell membrane corrects abnormal cellular proliferation and decreases inflammation-associated carcinogenesis. This is exemplified by cancer-preventive effects of n-3 PUFAs as fat sources for gastrointestinal cancers.