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

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.

Keywords: chemotherapy; herbal supplement; moringa oleifera; obesity; triple negative breast cancer.

Figure 1

Moringa seed extract concentrate does not alter food intake, body weight, or chemotherapy-induced weight loss in C57BL/6J female mice with diet-induced obesity and TNBC. (A) Schematic representations of experimental design. (B) Average weekly food intake, (C) cumulative food intake, (D) weekly body weight change and (E) total body weight change (CTRL n = 5, Chemo n = 6, MC n = 5, and MC + Chemo n = 5). Data are shown as the mean ± SEM. * p < 0.05 and ** p < 0.01. Panels A and D were assessed by one-way ANOVA with Tukey’s multiple comparisons. Panels B and C were assessed by a two-way ANOVA with Tukey’s multiple comparisons.

Figure 2

Moringa seed extract concentrate protects against high-fat diet- and chemotherapy-induced increases in fasting glucose and improves insulin sensitivity in C57BL/6J female mice with diet-induced obesity and TNBC. (A) Terminal ITT, (B) terminal area under glucose response curve (AUC), (C) change in fasting blood glucose and (D) percent change in glucose AUC (CTRL n = 5, Chemo n = 6, MC n = 5, and MC + Chemo n = 5). Data are shown as the mean ± SEM. * p < 0.05. Panel (A) was assessed by a two-way ANOVA with Tukey’s multiple comparisons. Panels (B–D) were assessed by one-way ANOVA with Tukey’s multiple comparisons.

Figure 3

Moringa seed extract concentrate does not reduce tumor growth, has a negative interaction with chemotherapy and reduces tumor angiogenesis in C57BL/6J female mice with diet-induced obesity and TNBC. (A) Inhibition of cell viability after 24-h continuous exposure to varying concentrations of doxorubicin, cyclophosphamide or MC in MDA-MB-231 cells (n = 10 per condition). (B) Tumor volumes over the treatment period and (C) terminal tumor mass (CTRL n = 5, Chemo n = 6, MC n = 5, and MC + Chemo n = 5). (D) Representative H&E (20x, scale = 100 µm), CD31+ (20x, scale = 100 µm) and (E) quantification of CD31+. Data are shown as the mean ± SEM. * p < 0.05. Panel (A) was assessed with a four parameter nonlinear regression. Panel (B) was assessed by a mixed-model ANOVA with Tukey’s multiple comparisons. Panels (C,E) were assessed by one-way ANOVA with Tukey’s multiple comparisons.

Figure 4

Moringa seed extract concentrate (MC) in combination with chemotherapy (chemo) alters both human and mouse genes in tumors of C57BL/6J female mice with diet-induced obesity and TNBC. (A) Heat map visualization of the top 30 dose-responsive canonical signaling pathways following chemo, MC or MC + Chemo treatment evaluated in murine or human genomes. (B,C) Heat map visualization of top 15 differentially expressed (B) murine and (C) human genes. Transcripts were filtered based on the following criteria: q < 0.05, base mean > 30 and fold change > 1.5.