Cytotoxic components from the leaves of Erythrophleum fordii induce human acute leukemia cell apoptosis through caspase 3 activation and PARP cleavage

  • Bioorg Med Chem Lett. 2021 Jan 1:31:127673. doi: 10.1016/j.bmcl.2020.127673.
Phuong Hien Thi Vo  1 ,  Thuy Duong Thi Nguyen  2 ,  Hoa Thanh Tran  2 ,  Yen Nhi Nguyen  1 ,  Minh Thu Doan  2 ,  Phi Hung Nguyen  3 ,  Giang Thi Kim Lien  4 ,  Dao Cuong To  5 ,  Manh Hung Tran  6
Affiliations
  • 1. University of Science, Vietnam National University Hochiminh City, 227 Nguyen Van Cu, District 5, Hochiminh City 748000, Viet Nam.
  • 2. Biomedical Science Department, VNUK Institute for Research & Executive Education, The University of Danang, 158A Le Loi, Hai Chau District, Danang City 551000, Viet Nam.
  • 3. Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay District, Hanoi 122100, Viet Nam.
  • 4. The University of Danang, 41 Le Duan, Hai Chau District, Danang City 551000, Viet Nam.
  • 5. Faculty of Pharmacy, Phenikaa University, Yen Nghia, Ha Dong District, Hanoi 12116, Viet Nam; Phenikaa Research and Technology Institute (PRATI), A&A Green Phoenix Group JSC, 167 Hoang Ngan, Cau Giay District, Hanoi 11313, Viet Nam. Electronic address: [email protected].
  • 6. University of Science, Vietnam National University Hochiminh City, 227 Nguyen Van Cu, District 5, Hochiminh City 748000, Viet Nam. Electronic address: [email protected].
PMID: 33161122 DOI: 10.1016/j.bmcl.2020.127673
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 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.

Keywords
Caesalpinioideae; Cassaine diterpenoid; Erythrofordins; Erythrophleum fordii oliver; Human leukemia cancer cells; Molecular docking.