Oligomeric proanthocyanidins from rabbiteye blueberry leaves inhibits the proliferation of human T-cell lymphotropic virus type 1-associated cell lines via apoptosis and cell cycle arrest

Abstract

Highlights: • Blueberry leaves strongly inhibited growth of HTLV-1-associated cell lines. • The most effective fraction contained highly oligomeric proanthocyanidins (OPAs). • OPA induced apoptosis and G2/M cell cycle arrest in HTLV-1-associated cell lines. • OPA-induced apoptosis required death receptor-mediated caspase-dependent pathways. • OPA-induced G2/M arrest resulted from down-regulation of cyclin B1 and cdc2. Abstract: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease caused by human T-cell lymphotropic virus type 1 (HTLV-1). As ATLL develops over many years, daily diet may play an important role in its occurrence. In this study, we investigated the growth inhibitory effect of extracts of blueberry leaf fractions on HTLV-1-associated cell lines. The most effective fraction contained highly oligomeric proanthocyanidins (OPA) with a mean degree of polymerization of 3.1. Cell growth inhibition by the OPA fraction was higher in all HTLV-1-associated cell lines than in the MOLT-4 HTLV-1-negative T-cells. It inhibited growth of the HTLV-1-infected T-cell line MT2 and ATLL-derived cell line Su9T01 by inducing apoptosis and G2/M cell cycle arrest. OPA fraction-induced apoptosis of HTLV-1-associated cells required death receptor-mediated caspase-dependent pathways. Treatment-induced G2/M arrest resulted from down-regulation of cyclin B1 and cdc2. The blueberry leaf OPA fraction may be a source of novel compounds for reducing the risk of developing ATLL.

Keywords

• Oligomeric proanthocyanidins
• Blueberry leaves
• Adult T-cell leukemia
• HTLV-I
• Apoptosis
• G2/M cell cycle arrest