Uvangoletin induces mitochondria-mediated apoptosis in HL-60 cells in vitro and in vivo without adverse reactions of myelosuppression, leucopenia and gastrointestinal tract disturbances

Abstract

This study investigated the cytotoxic effect of uvangoletin on HL-60 cells, and the effects of uvangoletin on myelosuppression, leucopenia, gastrointestinal tract disturbances and the possible cytotoxic mechanisms by using CCK-8, flow cytometry, western blot, xenograft, cyclophosphamide-induced leucopenia, copper sulfate-induced emesis and ethanol-induced gastric mucosal lesions assays. The results of CCK-8, flow cytometry and western blot assays indicated that uvangoletin showed the cytotoxic effect on HL-60 cells and induced the apoptosis of HL-60 cells by downregulating the expression levels of anti-apoptotic proteins (Survivin, Bcl-xl and Bcl-2), upregulating the expression levels of pro-apoptotic proteins (Smac, Bax, Bad, c-caspase-3 and c-caspase-9), and promoting the release of cytochrome c from mitochondria to cytoplasm. Further, the results of xenograft assay suggested that uvangoletin inhibited the HL-60-induced tumor growth without adverse effect on body weight of nude mice in vivo by regulating the expression levels of above apoptotic proteins. The results indicated that the reductions of WBCs count and thighbone marrow granulocytes percentage in cyclophosphamide-induced leucopenia assay, the incubation period and number of emesis in copper sulfate-induced emesis assay and the gastric mucosal lesions in ethanol-induced gastric mucosal lesions assay were not exacerbated or reversed by uvangoletin. In conclusion, the research preliminarily indicated that uvangoletin induced apoptosis of HL-60 cells in vitro and in vivo without adverse reactions of myelosuppression, leucopenia and gastrointestinal tract disturbances, and the pro-apoptotic mechanisms may be related to mitochondria-mediated apoptotic pathway.

Preparation and characterization of erythrocyte membrane cloaked PLGA/arsenic trioxide nanoparticles and evaluation of theirin vitroanti-tumor effect

“…HL60 cells were used to evaluate the in vitro anti-tumor effect of RPANs by CCK8 assay. 33 The inhibitory rates ( Fig. 8B ) of ATO solution and the RPANs system were 26.1% and 19.9%, respectively, after 12 h incubation, which indicated a similar level of anti-tumor efficacy of RPANs and ATO solution in the HL60 tumor cell model.…”

Curcumin Generates Oxidative Stress and Induces Apoptosis in Adult Schistosoma mansoni Worms

“…Activation of the apoptosome can ultimately activate effector caspase and apoptosis [63–65]. A wide range of chemicals or natural compounds can stimulate the formation of ROS and trigger apoptosis [66–67]. High concentrations of CUR (at 25 and 50 μM) promote the formation of ROS in different cell lines, whereas low CUR (at 10 μM) usually diminishes the formation of ROS [28, 68–71].…”

A comprehensive review on the chemical constituents, sesquiterpenoid biosynthesis and biological activities of Sarcandra glabra

“…Extensive in vitro and in vivo investigations have been conducted over the past decades on various cell lines, focusing on plant extracts [ 164 – 169 ], medicinal formulations [ 170 – 173 ], and chemical constituents. The main cytotoxic chemical components identified from S. glabra include sesquiterpenoids [ 4 , 17 , 22 , 33 ], coumarins [ 78 , 79 , 85 , 174 ], flavonoids [ 175 – 177 ], and polysaccharides [ 146 , 148 , 178 – 182 ].…”

“…Validated through an in vivo xenograft assay, a preliminary study by Zheng et al [ 175 ] validated the antitumour effects of uvangoletin ( 272 ) on HL60 cells. The proposed mechanism involves the interaction between mitochondria-mediated apoptotic proteins, leading to cytochrome C release into the cytosol and subsequent activation of apoptosis-executing caspases.…”