Cytotoxic components from the leaves of Erythrophleum fordii induce human acute leukemia cell apoptosis through caspase 3 activation and PARP cleavage
| Autor: | Manh Hung Tran, Thuy Thi Nguyen, Giang Thi Kim Lien, Yen Nhi Nguyen, Hoa Thanh Tran, Dao Cuong To, Phuong Hien Thi Vo, Minh Thu Doan, Phi Hung Nguyen |
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| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Cell Survival Poly ADP ribose polymerase Clinical Biochemistry Poly (ADP-Ribose) Polymerase-1 Pharmaceutical Science Apoptosis Caspase 3 Poly(ADP-ribose) Polymerase Inhibitors Biochemistry Structure-Activity Relationship Cell Line Tumor Drug Discovery Humans Cytotoxic T cell Cytotoxicity Molecular Biology Cell Proliferation Caspase-9 Dose-Response Relationship Drug Molecular Structure biology Plant Extracts Chemistry Organic Chemistry Fabaceae biology.organism_classification Antineoplastic Agents Phytogenic Molecular biology Plant Leaves Erythrophleum fordii Cancer cell biology.protein Molecular Medicine Drug Screening Assays Antitumor |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 31:127673 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2020.127673 |
| Popis: | 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 IC50 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. |
| Databáze: | OpenAIRE |
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