1. Cytotoxic components from the leaves of Erythrophleum fordii induce human acute leukemia cell apoptosis through caspase 3 activation and PARP cleavage.
- Author
-
Vo PHT, Nguyen TDT, Tran HT, Nguyen YN, Doan MT, Nguyen PH, Lien GTK, To DC, and Tran MH
- Subjects
- Antineoplastic Agents, Phytogenic chemistry, Antineoplastic Agents, Phytogenic isolation & purification, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Models, Molecular, Molecular Structure, Plant Extracts chemistry, Plant Extracts isolation & purification, Plant Leaves chemistry, Poly (ADP-Ribose) Polymerase-1 metabolism, Poly(ADP-ribose) Polymerase Inhibitors chemistry, Poly(ADP-ribose) Polymerase Inhibitors isolation & purification, Structure-Activity Relationship, Antineoplastic Agents, Phytogenic pharmacology, Apoptosis drug effects, Caspase 3 metabolism, Fabaceae chemistry, Plant Extracts pharmacology, Poly (ADP-Ribose) Polymerase-1 antagonists & inhibitors, Poly(ADP-ribose) Polymerase Inhibitors pharmacology
- Abstract
Cassaine diterpenoids as erythrofordins A-C (1-3), pseudo-erythrosuamin (4), and erythrofordin U (5) isolated from the leaves of Vietnamese Erythrophleum fordii Oliver were tested cytotoxic activity against human leukemia cancer cells. The results showed that these metabolites exhibited dose-dependent cytotoxicity against human leukemia HL-60 and KG cells with IC
50 values ranging from 15.2 ± 1.5 to 42.2 ± 3.6 µM. Treatment with erythrofordin B led to the apoptosis of HL-60 and KG cells due to the activation of caspase 3, caspase 9, and poly (ADP-ribose) polymerase (PARP). Erythrofordin B significantly increased Bak protein expression, but downregulated the anti-apoptotic protein Bcl-2, in HL-60 cells. In silico results demonstrated that erythrofordin B can bind to both the procaspase-3 allosteric site and the PARP-1 active site, with binding energies of -7.36 and -10.76 kcal/mol, respectively. These results indicated that the leaves of Vietnamese E. fordii, which contain cassaine diterpenoids, can induce the apoptosis of human leukemia cancer cells., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF