The Anticancer and Antioxidant Effects of Muscadine Grape Extracts on Racially Different Triple-negative Breast Cancer Cells

Abstract

Background/aim: Triple-negative breast cancer (TNBC) is the most aggressive subtype, predominant in African American women. In this study, the antioxidant/anticancer activity of muscadine grape extracts and the role of their phenolic and flavonoid contents in exerting these properties were investigated in TNBC cells.

Materials and methods: Berry extracts from muscadine genotypes were investigated for total phenolic content (TPC), total flavonoid content (TFC), antioxidant capacity, and anticancer effects using breast cancer cell lines, representing Caucasians and African Americans.

Results: The antioxidant activity was associated with high TPC content. Extracts showed cytotoxicity up to 78.6% in Caucasians and 90.7% in African American cells, with an association with high antioxidant capacity. There was a strong correlation between TPC and anticancer/antioxidant activities.

Conclusion: The anticancer and antioxidant effects of muscadine grapes are attributed to the TPC of extracts, which showed a stronger positive correlation with growth inhibition of African American breast cancer cells compared to Caucasians.

Keywords: MDA-MB-231; MDA-MB-468; TNBC; anticancer; antioxidant; flavonoids; phenolic.

Figure 1.

Illustration showing the correlation of MM-231/MM-468 cell growth inhibition versus TPC (A, B), TFC (C, D) and DPPH inhibition (E, F). Each point represents the genotype value for each of the two traits. Statistically significant differences represented by probability levels at *p<0.05, **p<0.01, and ***p<0.001 are calculated [n=196, r_0.05=0.140, r_0.01=0.184, r_0.001=0.233].

Figure 2.

PCA scatter plots of different traits. TPC: Total phenolic content; TFC: total flavonoid content; DPPH: antioxidant effect; MM-231 (Caucasian breast-cancer cells) and MM-468 (African American breast-cancer cells) anticancer activity. According to the PCA model, 53.16% and 18.55% of the variance were explained by the PC1 (TPC) and the PC2 (TFC) principal components, respectively.

Figure 3.

Hierarchical clustering of phytochemical content and biological activities of muscadine population (196 genotypes). Data related to TPC, TFC, antioxidant activity, and anticancer activity for Caucasian (MM-231) and African American (MM-468) breast-cancer cells are presented as a percentage. The log2-transformed values of each character are represented by colors. Green boxes indicate higher levels and red boxes indicate lower levels compared to the control. The color change is proportional to the accumulation/activity levels.

Figure 4.

Frequency distribution of berry metabolomic traits and consequent biological activities of the muscadine population (n=196). Population means of each trait are indicated.