A low carbohydrate, high protein diet combined with celecoxib markedly reduces metastasis

Abstract

We recently demonstrated that both murine and human carcinomas grow significantly slower in mice on low carbohydrate (CHO), high protein diets than on isocaloric Western diets and that a further reduction in tumor growth rates occur when the low CHO diets are combined with the cyclooxygenase-2 inhibitor, celecoxib. Following upon these studies, we asked herein what effect low CHO, high protein diets, with or without celecoxib, might have on tumor metastasis. In the highly metastatic 4T1 mouse mammary tumor model, a 15% CHO, high protein diet supplemented with celecoxib (1 g/kg chow) markedly reduced lung metastases. Moreover, in longer-term studies using male Transgenic Adenocarcinoma of the Mouse Prostate mice, which are predisposed to metastatic prostate cancer, the 15% CHO diet, with and without celecoxib (0.3 g/kg chow), gave the lowest incidence of metastases, but a more moderate 25% CHO diet containing celecoxib led to the best survival. Metabolic studies with 4T1 tumors suggested that the low CHO, high protein diets may be forcing tumors to become dependent on amino acid catabolism for survival/growth. Taken together, our results suggest that a combination of a low CHO, high protein diet with celecoxib substantially reduces metastasis.

Polymeric Nanoparticles Induce NLRP3 Inflammasome Activation and Promote Breast Cancer Metastasis

“…Also, systemic inflammation and TNFα have been reported to promote lung metastasis . Moreover, celecoxib, an anti‐inflammation drug, was reported to significantly reduce cancer metastasis . These findings suggest that inflammation is correlated with homing of circulating tumor cells.…”

All Trans Retinoic Acid, Transforming Growth Factor β and Prostaglandin E2 in Mouse Plasma Synergize with Basophil-Secreted Interleukin-4 to M2 Polarize Murine Macrophages

“…Understanding all the factors involved in skewing is a key first step towards being able to manipulate this skewing to reduce the severity of these diseases. For example, while PGE 2 has both pro and anti-inflammatory properties, many tumours secrete PGE 2 to promote their own growth by skewing the immune system to a “healing” M2 phenotype and we as well as many others have shown that you can prevent as well as slow down the growth of many tumours with COX2 inhibitors [45]. As well, since atherosclerosis is promoted by M1 macrophages [46] and asthma and allergies are worsened by M2 skewed macrophages, reducing ATRA, PGE 2 and/or TGFβ may prove efficacious in reducing the symptoms of allergies, asthma and the incidence and progression of cancer while increasing these factors might reduce certain forms of heart disease.…”

Impact of Weight Loss on Plasma Leptin and Adiponectin in Overweight-to-Obese Post Menopausal Breast Cancer Survivors

“…In post-menopausal women, limiting caloric intake rather than increasing energy expenditure via physical activity is the key to achieving weight loss [ 10 ]. Of the dietary patterns used for weight loss, those that have received the most attention, low carbohydrate or low fat, are the same patterns that are at the center of a controversy about dietary approaches for breast cancer prevention and control [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. In both weight control and cancer control, many studies have focused on low-fat diets; however, proponents of low carbohydrate diets report that high carbohydrate intake results in higher plasma insulin levels and promotes lipogenesis [ 25 ]; hence the popularity of low-carbohydrate diets for weight loss among the general population.…”