Anthocyanins induce apoptosis in several cancer cell types

Apoptosis Induction

In addition to the uncontrolled cell proliferation, resistance to apoptosis (programmed cell death) is another important hallmark of cancer cells. Therefore, both proliferation and apoptosis of cells are critical points to target for chemoprevention of fruits and vegetables. Anthocyanin-rich extracts from berries or pure anthocyanins have exhibited as inducers of apoptosis in variable premalignant and malignant cells in vitro.

It was found that delphinidin 3-sambubioside induced apoptosis in human leukemia cells through a reactive oxygen species (ROS)-mediated mitochondrial pathway. Cyanidin-3-rutinoside isolated from the black raspberry induced apoptosis selectively towards HL-60 cells in a dose- and time-dependent manner through ROS-dependent activation of p38 MAPK and JNK, which contributed to cell death by activating the mitochondrial pathway without cytotoxic effects on normal cells.

Cyanidin-3-glucoside induced apoptosis in two human leukemia cell lines through modulation of p53 and bax protein expression. Cyanidin 3-glucoside and peonidin 3-glucoside induced caspase-3 activation, chromatin condensation, and cell death. The occurrence of apoptosis induced by malvidin was confirmed in human gastric adenocarcinoma cells by apoptotic bodies formation, caspase-3 activation and poly(ADP-ribose) polymerase proteolysis. Delphinidin treatment of PC3 prostate carcinoma cells resulted in a dose-dependent induction of apoptosis and cells arrest in G2-M phase. This induction of apoptosis appeared to be related to activation of caspases.

Anti-inflammatory Effects

Inflammatory cells are implicated in the tumor microenvironment and play a crucial role in tumor development and progression. The microenvironment of many human cancers is rich in cytokines, chemokines, and inflammatory enzymes.

Anthocyanins exhibit their anti-inflammation effect largely through targeting NF-κB pathway and cycloxygenase-2 (COX-2) gene. Anthocyanin-rich extracts from berries and pure anthocyanins exhibited inhibition of the mRNA and/or protein expression of NF-KB and COX-2 in multiple cell types.

Anti-angiogenic Activity

Angiogenesis is another key regulator for cancer progression which is defined as new blood vessel formation. Vascular endothelial growth factor (VEGF) is a key stimulator of angiogenesis. VEGF is another target to prevent or treat many cancers.Wild blueberry, bilberry, raspberry seeds, and strawberry suppressed significantly both H2O2- and TNF-alpha-induced VEGF expression by human keratinocytes in the following order: wild blueberry > raspberry seed > strawberry > bilberry and wild blueberry > bilberry > raspberry seed > strawberry. The anthocyanin-rich extract of black raspberries showed inhibitory effect on VEGF expression through inhibition of the phosphoinositide 3-kinase/Akt pathway in JB6 cells.

Anti-invasiveness

Tumor metastasis is the most important cause of cancer death and various treatment strategies have targeted preventing the occurrence of metastasis. The degradation of basement membrane collagen by proteolysis is an early and critical invasion event. Matrix metalloproteinases (MMP) and plasminogen activators responsible for regulating basement membrane degradation, as well as their inhibitors, have been studied for anthocyanin anti-invasive activity.

The cyanidin 3-rutinoside/3-glucosides extracted from mulberry (Morus alba L) exhibited an inhibitory effect on the migration and invasion of a human lung cancer cell line through decreasing the expressions of MMP-2 and urokinase-plasminogen activator (u-PA) in a dose-dependent manner and enhancing the expression of tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and plasminogen activator inhibitor (PAI). Major anthocyanins extracted from black rice, peonidin 3-glucoside and cyanidin 3-glucoside, inhibited the invasion of SKHep-1 cells. This effect was associated with a reduced expression of MMP-9 and u-PA.

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