Cytotoxic Activity of Vietnamese Morus alba Leaf Compounds Against Human Leukemia Cells: In Vitro and In Silico Evaluations
Journal: Revista Brasileira de Farmacognosia/ BRAZILIAN JOURNAL OF PHARMACOGNOSY, WoS(SCIE), Q2
Author: Nguyễn Tấn Khanh - Trường Đại học Đông Á
Abstract:
In this study, bioassay-guided fractionation of the leaves of Vietnamese Morus alba L., Moraceae, led to the isolation of a series of prenylated flavonoids and benzofurans. These compounds were evaluated for their cytotoxic activities against several human cancer cell lines in vitro. Among them, moracin C exhibited the most potent cytotoxicity against human leukemia HL-60 cells with an IC50 value of 6.7 ± 0.8 µM. Mechanistic investigations revealed that moracin C induced apoptosis through activation of caspase-3, caspase-9, and poly (ADP-ribose) polymerase, key components of the intrinsic apoptotic pathway. Further in silico molecular docking studies demonstrated that moracin C showed a favorable binding affinity for caspase-3 (− 6.9 kcal/mol), forming hydrogen bonds with Arg64 and Arg207, and hydrophobic interactions with Cys163 and Phe256, which are important residues for caspase-3 activation. Additionally, moracin C exhibited binding affinity for poly (ADP-ribose) polymerase (− 9.1 kcal/mol), interacting via hydrogen bonds with Tyr907 and Gly894, and hydrophobic contact with Tyr896. To further confirm these results, molecular dynamics simulations over 100 ns were performed. The moracin C–caspase-3 complex displayed initial instability but reached equilibrium after 60 ns, indicating a dynamic yet stable interaction, while the moracin C– poly (ADP-ribose) polymerase complex showed high stability with minimal structural fluctuations. Our study provides strong evidence that moracin C, a key component isolated from M. alba leaves, exerts its cytotoxic effects by promoting apoptosis through both caspase activation and poly (ADP-ribose) polymerase inhibition. These findings may support the therapeutic potential of M. alba and moracin C in the development of novel treatments for human leukemia.
DOI: Cytotoxic Activity of Vietnamese Morus alba Leaf Compounds Against Human Leukemia Cells: In Vitro and In Silico Evaluations | Revista Brasileira de Farmacognosia