Stability of blueberry anthocyanin, anthocyanidin and pyranoanthocyanidin pigments and their inhibitory effects and mechanisms in human cervical cancer HeLa cells

Abstract

Anthocyan-rich foods have attracted lots of attention because of their potential biological and pharmacological applications. Anthocyanins richly exist in blueberry fruits and have been proved to possess various bioactive properties. Despite the potential application of anthocyanins in the food, pharmaceutical and cosmetic industries, their use is limited because of their relative instability. Recently, much attention has been given to a particular family of anthocyanin derivatives, the pyranoanthocyanins that have been indicated to have higher stability than the original anthocyanins. However, the anti-cancer activity of pyranoanthocyanins is largely unknown. The objective of this study was to conduct a comparative analysis on the stability and anti-cancer activities of anthocyanins, anthocyanidins and pyranoanthocyanidins. Pyranoanthocyanidins exhibited the highest stability in the pH range 3.0–9.0, while anthocyanidins had the strongest inhibition on HeLa cells among the three anthocyan pigments. All the anthocyan pigments could effectively induce cell cycle arrest at the G₂/M phase in conjunction with a marked increase in the expression of the p53 protein. Exposure of HeLa cells to three anthocyan pigments caused pronounced late apoptosis that might be involved in the activation of the p38 MAPK/p53 signaling pathway. These findings suggest that anthocyanidins and pyranoanthocyanidins might be more promising anti-cancer agents than anthocyanins and warrant further evaluation regarding the molecular mechanisms.