Isobavachalcone, a Chalcone Constituent of Angelica keiskei, Induces Apoptosis in Neuroblastoma

Abstract

Six chalcones from Angelica keiskei KOIDZUMI (Ashitaba in Japanese) and two chalcones from Humulus lupulus L. (hop) were examined for their cytotoxicity in two human neuroblastoma cell lines (IMR-32 and NB-39) and normal cells (primary culture of rat cerebellar granule cells) by [3-(4,5)-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. All chalcones exhibited cytotoxicity against neuroblastoma cells, and two of them (isobavachalcone and xanthoangelol H) had no effect on normal cells even at high concentration (10 ؊4 M) exposure. Typical morphologic features of apoptosis, including cell shrinkage, chromatin condensation, nuclear fragmentation and formation of apoptotic bodies, were observed in isobavachalcone-treated cells by Hoechst 33342 staining. Western blot analysis showed that isobavachalcone significantly reduced pro-caspase-3 and pro-caspase-9, and subsequently increased the level of cleaved caspase-3 and cleaved caspase-9 in both neuroblastoma cell lines. Moreover, Bax was markedly induced by isobavachalcone application. These results suggest that isobavachalcone induces apoptotic cell death in neuroblastoma via the mitochondrial pathway and has no cytotoxicity against normal cells. Therefore, isobavachalcone may be applicable as an efficacious and safe drug for the treatment of neuroblastoma.

Dietary chalcones with chemopreventive and chemotherapeutic potential

“…Another component of this plant, isobavachalcone (15), induced apoptosis in neuroblastoma by downregulation of pro-caspase 3 and 9 followed by upregulation of cleaved caspase 3 and 9 and Bax induction, similar to the effects of chalcone (10) in human bladder cancer cells [128,158]. Moreover, no cytotoxicity was observed against nontransformed cells [128]. A similar mechanism was described for isolespeol (39), isolated from the traditional starch crop Artocarpus communis cultivated in tropical and subtropical regions [33], in human liposarcoma SW-872 cells [187,188].…”

“…In addition, apoptosis induction through ROS generation by xanthoangelol (33), a major constituent of Angelica keiskei, was described by Motani et al in neuroblastoma [121]. Another component of this plant, isobavachalcone (15), induced apoptosis in neuroblastoma by downregulation of pro-caspase 3 and 9 followed by upregulation of cleaved caspase 3 and 9 and Bax induction, similar to the effects of chalcone (10) in human bladder cancer cells [128,158]. Moreover, no cytotoxicity was observed against nontransformed cells [128].…”

In Vitro Effect of 8-Prenylnaringenin and Naringenin on Fibroblasts and Glioblastoma Cells—Cellular Accumulation and Cytotoxicity

“…In this study we compared the cytotoxicity of naringenin and 8-prenylnaringenin ( Figure 1) against normal fibroblasts and U-118 MG glioma cells due to reports that substitution of the prenyl group increases the hydrophobicity of flavonoids and may led to its higher cellular accumulation [26] and in consequence higher toxicity against cancer cells [27]. Neutral red assay showed that both flavonoids exerted stronger inhibitory effect on the cancer cell line as compared with normal cells (Figure 2).…”

Antitumour and Acute Toxicity Studies of 4-(pyridin-4-yl)-6-(thiophen-2-yl)pyrimidin-2(1<em>H</em>)-one Against Ehrlich Ascites Carcinoma and Sarcoma-180

“…They have serve as lead compounds for the discovery of new anti-inflammatory, anti-infective, anti-cancer and antioxidant agents [24]. A literature report shows that chalcones are capable of inducing the death of cancer cells through apoptosis, as well as subsiding the mitochondrial membrane potential [25][26][27].…”