Fruits and barks extracts of Zanthozyllum heitzii a spice from Cameroon induce mitochondrial dependent apoptosis and Go/G1 phase arrest in human leukemia HL-60 cells

Biological research: BR

Guru Kumar Santosh¹  Jeanne Yonkeu Ngogang¹  Emmanuel Mouafo Tekwu²  Shashi Bhushan²  Tü³  lin Askun³  Constant Anatole Pieme⁴  Ajit Kumar Saxena⁵  Hatice Aydeniz⁶ 

[1] 1, Yaoundé, Cameroon;Cancer Pharmacology Division, Indian Institute of Integrative Medicine, India;Department of Biochemistry and Physiological Sciences, Faculty of Medicine and Biomedical Sciences, University of YaoundéDepartment of Biology, Faculty of Sciences and Arts, University of Balikesir, Cagis Campus, Turkey;Laboratory for TB research, Biotechnology Centre, Faculty of Science, University of Yaoundé

关键词: Zanthozyllum heitzii;    Syringic acid;    Apoptosis;    HL-60 cells;    ROS;    Mitochondrial membrane potential;   

DOI  :  10.1186/0717-6287-47-54

学科分类：生物科学（综合）

来源: BioMed Central

【 摘 要 】

Zanthoxylum heitzii is a spice used to prepare several dishes and to treat tumors, syphilis, malaria, cardiac palpitations, urogenital infections in the west region of Cameroon, but the antitumor mechanisms and chemical composition are not yet investigated. This study was aimed to determine the antiproliferative effects of four extracts from the fruits and barks of Zanthoxyllum heitzii (Rutaceae) on apoptosis in human promyelocytic cells, their mechanisms and the chemical composition. The 3-(4, 5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the fifty percent inhibition (IC50) concentration of the cell lines after treatment. The effect on morphology was observed using a light or fluorescence microscopy. The rate of apoptosis and the cell cycle were measured using flow cytometry (FCM). The phytochemical analysis of the extract was carried with HPLC/MS methods. The phytochemical analysis of the extracts indicated the presence of four known polyphenols (Syringic acid, Juglon, Luteolin and Myricetin) in both fruits and barks of Z. heitzii but in different quantities. Syringic acid and Myricetin concentrations were between 17-21 fold higher in the fruits than the stem bark. Rhamnetin (393.35 μg/mL) and Oleuropein (63.10 μg/mL) were identified only in the stem barks of Z. heitzii. Among the four extracts tested for cytotoxicity properties, only the methanol extract of fruits and barks significantly inhibited cell proliferation of HL-60 cells with IC50 value of 20 μg/mL and 12 μg/mL respectively. HL-60 cells treated with Z. heitzii extracts significantly produced reactive oxygen species (ROS) with concurrent loss of mitochondrial membrane potential (MMP). Modifications in the DNA distribution and enhanced of G1/G0 phase cell cycle arrest were observed in a concentration dependent manner. Polyphenols from Z. heitzii plant exert inhibitory effect on HL-60 cells through the reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential and cell cycle destabilization.

【 授权许可】

CC BY