A novel homospermidine conjugate inhibits growth and induces apoptosis in human hepatoma cells

Abstract

Aim: To elucidate the mechanism responsible for the antiproliferative effects of a novel homospermidine conjugate, anthracenylmethyl homospermidine (ANTMHspd), in the human hepatoma BEL-7402 cell line. Methods: The viability of the cells was assessed by MTT assay and the trypan blue dye exclusion method. Morphological changes were observed by fluorescence microscopy with Hoechst 33258 staining. Cell cycle distribution, apoptosis, and mitochondrial membrane potential were measured by flow cytometry. Protein expression was detected by Western blot analysis. Results: ANTMHspd strongly decreased BEL-7402 cell proliferation in a dose-and time-dependent manner. Hoechst 33258 staining and the flow cytometry assay showed that ANTMHspd induced cell apoptosis and cell cycle perturbation. Furthermore, ANTMHspd could induce mitochondrial membrane potential loss and cytochrome c release and enhance cleaved caspase-3, cleaved caspase-9, and Bax protein expression without caspase-8 activation. ANTMHspd could also decrease the expression of Bcl-2 and cytochrome c in mitochondria. In addition, the specific inhibitors of caspase-9 and caspase-3 almost abolished the ANTMHspd-induced caspase-9 and caspase-3 activation, respectively. Conclusion: ANTMHspd could induce BEL-7402 cell apoptosis via the mitochondrial/caspase-dependent pathway and the Bcl-2 family was involved in the control of apoptosis.

RETRACTED ARTICLE: NPC-16, a novel naphthalimide–polyamine conjugate, induced apoptosis and autophagy in human hepatoma HepG2 cells and Bel-7402 cells

“…Our data demonstrated that the antiproliferative effect of NPC-16 was obviously different between human Many data demonstrated that polyamine derivatives or naphthalimides derivatives could induce tumor cells apoptosis [14,15], however, the reports about naphthalimidepolyamine conjugate induced tumor cell apoptosis are rare. Our results revealed that NPC-16 induced Bel-7402 cells apoptosis via caspase-dependent pathway, this result was similar with ANTMHspd, an anthracenylmethyl-homospermidine conjugate [16]. Nevertheless, pre-incubated with Z-VAD-FMK, an extensive caspase inhibitor, only partly inhibited NPC-16-induced cell apoptosis in HepG2 cells.…”

“…We found that the NPC-16-induced loss of MMP was accompanied with the release of cytochrome c from mitochondria into cytoplasm, suggesting that the NPC-16 induced cell apoptosis was correlated with mitochondrial dysfunction. This effect is similar to that of ANTMHspd [16] but not that of DENspm [24], for DENspm only triggered the release of cytochrome c from mitochondria without decreasing the MMP of mitochondria. Previous studies have shown that Bcl-2 family proteins were usually involved in polyamine conjugate induced mitochondria apoptotic signal pathway [25,26].…”

“…Nevertheless, pre-incubated with Z-VAD-FMK, an extensive caspase inhibitor, only partly inhibited NPC-16-induced cell apoptosis in HepG2 cells. This was different with ANTMHspd which was induced Bel-7402 cells caspase-dependent apoptosis only via mitochondrial pathway, while NPC-16 induced HepG2 cells apoptosis via both mitochondrial pathway and death receptor pathway [16], suggesting that the mother nuclide of polyamine conjugates determined the molecular apoptotic mechanism and polyamine, in spite of natural polyamines or synthetical polyamines, only a tumor targeted vector. Our previous data demonstrated that naphthalimide-polyamine conjugates inhibited mTOR signal pathway [17], and mTOR was often involved in cell autophagy [18].…”

Reactive oxygen species (ROS) accumulation induced by mononaphthalimide-spermidine leads to intrinsic and AIF-mediated apoptosis in HeLa cells

“…Some research indicates a relationship between Bcl-2 family and polyamine conjugation-induced apoptosis (29,30). Recently, a downregulation of Bcl-2, p-Bad and Bcl-xL in HepG2 cells with naphthalimide-polyamine conjugate treatment was reported (21).…”

Pseudomonas aeruginosa: Mannose Sensitive Hemagglutinin Inhibits the Growth of Human Hepatocarcinoma Cells via Mannose-Mediated Apoptosis

“…It has been previously shown that live P. aeruginosa can induce apoptosis via both extrinsic and intrinsic apoptosis pathways, however, apoptosis is not induced by heat-killed P. aeruginosa [27][28][29]. In addition, both pathways have been shown to be functional in Hep G2 [30,31] and BEL-7402 cells [32,33]. In the present study, Hep G2 and BEL-7402 cells exposed to PA-MSHA underwent apoptosis accompanied by up-regulated expression of caspase-3 and caspase-8, but not caspase-9.…”