Molecular mechanisms of curcumin-induced apoptosis in lymphoid malignant cells

ABSTRACT

Curcumin [diferuloylmethane], a natural compound isolated from the plant Curcuma longa, has been shown to possess potent anti-tumour and anti-oxidative properties. The mechanism by which curcumin initiates apoptosis remains poorly understood. In the present study the effect of curcumin on the activation of apoptotic pathway in human lymphoma cells was investigated. Curcumin induces apoptosis in several primary effusion lymphoma [PEL] cell lines of B cell origin via inhibition of constitutively active AKT/PKB and subsequently loss of mitochondria membrane potential and activation of caspase-3. Pre-treatment of these cells with N-acetyl-cysteine, a scavenger of oxygen radical markedly prevented cell proliferation, apoptosis, de-phophorylation of AKI loss of mitochondrial membrane potential, activation of caspase3 and inhibition of XIAP suggesting a role for reactive oxygen species in this process. Altogether, these findings suggest a novel function for curcumin, acting as a suppressor of AKT activation in B-lymphoma cells by generating oxidative metabolites, leading to inhibition of proliferation via inducing loss of mitochondrial membrane potential and caspase-dependent apoptosis. Therefore, curcumin may have a future therapeutic role in lymphoma and possibly other malignancies with constitutive activation of AKT