Moringa Oleifera Seed Extract Concomitantly Supplemented with Chemotherapy Worsens Tumor Progression in Mice with Triple Negative Breast Cancer and Obesity

Elizabeth R. M. Zunica,Linda A. Gilmore,Christy White,Ann Coulter,John P. Kirwan,Shengping Yang

doi:10.3390/nu13092923

Elizabeth R. M. Zunica, Linda A. Gilmore + Show 4 more

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https://doi.org/10.3390/nu13092923

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Abstract

Triple negative breast cancer (TNBC) is an aggressive and highly metastatic breast cancer subtype with limited treatment options. Obesity and insulin resistance are associated with a worse prognosis in those with TNBC. Moringa oleifera (moringa) is a tropical edible plant used for both food and medicinal purposes and found to have anti-obesity and anti-cancer effects in vitro and in preclinical models. The anti-cancer effects of moringa seed extract alone and in combination with chemotherapy were evaluated in immunocompromised female mice with diet-induced obesity bearing MDA-MB-231-derived xenograft tumors. Moringa supplementation protected against high-fat diet- and chemotherapy-induced increases in fasting glucose and improved insulin sensitivity. Moringa supplementation alone did not attenuate tumor growth relative to chemotherapy alone, and in combination worsened tumor progression. Moringa supplementation alone reduced angiogenesis, but this effect was abrogated in combination with chemotherapy. Moringa supplementation may be an effective strategy to improve metabolic health in mice with obesity and TNBC and reduce angiogenesis in tumors, but may have a negative interaction when used as a concurrent complementary therapy. Caution should be taken when considering the consumption of moringa seed extracts while receiving chemotherapy for breast cancer treatment. Further investigations of alternative timings of moringa therapy are warranted.

Highlights

Chemo increased CYP2J2 gene expression relative to CTRL. These findings indicate that Moringa concentrate (MC) alters the transcriptomic effect of chemotherapy when given in combination with chemotherapy and minimally alters angiogenic and insulin transcriptomic pathways alone
Given the previously published efficacy of moringa seed and leaf extract to protect against high-fat diet-induced obesity in male mice, we sought to perform pre-clinical validation of the efficacy of moringa seed extract concentrate to improve metabolic parameters in female mice with high-fat diet-induced obesity and triple negative breast cancer (TNBC)
We observed an improvement in fasting glucose and whole body insulin sensitivity (AUC) with moringa alone compared to chemotherapy, but did not see this effect when moringa was combined with chemotherapy

Summary

Introduction

Cancer is a known comorbidity of obesity, and insulin resistance is associated with an increased risk for breast cancer [1]. Due to the link between obesity, insulin resistance and cancer, several FDA-approved antidiabetic therapies such as insulin sensitizers (thiazolidinediones), insulin secretagogues (sulfonylureas) and biguanides, which have been associated with the decrease in cancer incidence, are being investigated as anti-cancer therapies [5,6,7]. Moringa oleifera (moringa) is an edible tropical plant used for both food and medicinal purposes and found to have anti-obesity and antidiabetic effects in rats [8,9] and mice [10,11]. The leaves, bark, flowers, fruit, seeds and root of the moringa plant may be used to make herbal medicines due to the presence of a multitude of bioactive phytochemicals. Moringa seeds have much higher levels of ITCs, enriched in

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