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

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

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: cuong.todao@phenikaa-uni.edu.vn.
  • 6 University of Science, Vietnam National University Hochiminh City, 227 Nguyen Van Cu, District 5, Hochiminh City 748000, Viet Nam. Electronic address: tmhung@hcmus.edu.vn.
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.

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