Capability of Prenylflavanones present in Hops to Induce Apoptosis in a Human Burkitt Lymphoma Cell Line

Abstract

8-Prenylnaringenin (8-PN), a flavanone present in the female flower of hops (Humulus lupulus L.) and in some other plants (e.g. in Anaxagorea luzonensis A.Gray.) [1, 2] is known as being a very potent phytoestrogen [3]. As such it may accelerate proliferation analogous to estradiol in sensitive cell lines. The question was to be clarified whether it may contribute to growth of hormone dependent neoplasms when present in herbal preparations. We found instead antiproliferative and apoptosis inducing effects of 8–PN. We compared some side chain variants of 8-prenylnaringenin e.g. 8–geranylnaringenin, isolated also from hops and the synthetic variations 8–furanylmethylnaringenin, 8–cinnamylinaringenin. These were synthesized by a Mitsunobu reaction and Claisen rearrangement [4]. When applied to BJAB cells, grown in RPMI 1640 medium, these flavanones showed improved cytotoxic and apoptotic activities – only 8-furanylmethylnaringenin is not active. 8-Geranylnaringenin displayed noticeably improved apoptotic effects when compared to 8-PN. 8-Cinnamylnaringenin significantly induced apoptosis in BJAB cells at a concentration of 50µM. (Fig. 4). The apoptotic effect of 8-cinnamylnaringenin exceeded those of all other naringenins tested in this study. The induction of apoptosis is concentration dependent (11% apoptotic cells at 50µM and 38% at 100µM). Apoptosis was induced in a mitochondrial dependent manner. Despite low capacity to induce apoptosis, 8-PN induced a decrease of the mitochondrial membrane potential, too. However, 8-geranylnaringenin caused a change in the membrane potential at much lower concentration. At 100µM we noticed a saturation effect in decrease of mitochondrial membrane potential. But the greatest effect was demonstrated with 8-cinnamylnaringenin. Even at a concentration of 50µM, it is observed a transition in 77% of the BJAB cells. The potential of 8–PN is shown in an ex vivo experiment of a multi-drug resistant leukaemia blast.