Apigenin Induces Apoptosis in Primary Effusion Lymphoma.

The mechanisms that regulate induction of the antiapoptotic state and mitogenic signals in primary effusion lymphoma (PEL) are not well known. In efforts to identify novel approaches to block the proliferation of PEL cells, we found that apigenin (4′,5,7,-trihydroxyflavone), a flavonoid, induces apoptosis in a dose dependent manner in several PEL cell lines. Such effects of apigenin appear to result from suppression of the constitutively active AKT, FOXO transcription factor and GSK3. Our data also demonstrate that apigenin induces loss of mitochondrial membrane potential with subsequent release of cytochrome c and activation of caspase-3, followed by polyadenosin-5′-diphosphate-ribose polymerase (PARP) cleavage. Altogether, our findings suggest a novel function for apigenin, acting as a suppressor of AKT/PKB pathway in PEL cells, leading to the induction of caspase-dependent apoptosis. Therefore, apigenin may have a future therapeutic role in PEL and possibly other malignancies with constitutive activation of AKT/PKB pathway.