New Insights into the Mechanisms of Polyphenol from Plum Fruit Inducing Apoptosis in Human Lung Cancer A549 Cells Via PI3K/AKT/FOXO1 Pathway.

Abstract

Recent studies have been found that polyphenols from plums fruits can inhibit the proliferation of multiple cancer cells, while the molecular mechanism was unclear. This study aimed to investigate the molecular mechanism underlying the pro-apoptotic effect of purified plum polyphenols (PPP) on human lung cancer A549 cells. Quercitrin (quercetin-3-O-glucoside, 814.19 ± 40.71mg/g) was identified as the primary polyphenol in PPP via ultra high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS). PPP showed a strong capacity for inhibiting the proliferation of the A549 cells by inducing apoptosis, which was reflected by an increase in the Bax/Bcl-2 ratio. Additionally, the inhibitory rate of PPP on the A549 cells were higher than that of vitamin C when the treatment dose exceeded 160μg/mL. Transcriptome analysis suggested that PPP-induced apoptosis was closely associated with regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/forkhead box protein O 1 (FOXO1) pathway in the A549 cells. Subsequently, as an activator of AKT, SC79 was applied to confirm that the inhibition of AKT phosphorylation play an important role in the PPP-induced apoptosis of the A549 cells. These results illustrated the potential of PPP as a dietary compound for the prevention of cancer or for use during chemotherapy.