Cytotoxic Mechanism of Momilactones A and B against Acute Promyelocytic Leukemia and Multiple Myeloma Cell Lines

This is the first study clarifying the cytotoxic mechanism of momilactones A (MA) and B (MB) on acute promyelocytic leukemia (APL) HL-60 and multiple myeloma (MM) U266 cell lines. Via the MTT test, MB and the mixture MAB (1:1, w/w) exhibit a potent cytotoxicity on HL-60 (IC₅₀ = 4.49 and 4.61 µM, respectively), which are close to the well-known drugs doxorubicin, all-trans retinoic acid (ATRA), and the mixture of ATRA and arsenic trioxide (ATRA/ATO) (1:1, w/w) (IC₅₀ = 5.22, 3.99, and 3.67 µM, respectively). Meanwhile MB, MAB, and the standard suppressor doxorubicin substantially inhibit U266 (IC₅₀ = 5.09, 5.59, and 0.24 µM, respectively). Notably, MB and MAB at 5 µM may promote HL-60 and U266 cell Apoptosis by activating the phosphorylation of p-38 in the mitogen-activated protein kinase (MAPK) pathway and regulating the relevant proteins (Bcl-2 and Caspase-3) in the mitochondrial pathway. Besides, these compounds may induce G2 phase arrest in the HL-60 cell cycle through the activation of p-38 and disruption of CDK1 and cyclin B1 complex. Exceptionally, momilactones negligibly affect the non-cancerous cell line MeT-5A. This finding provides novel insights into the Anticancer property of momilactones, which can be a premise for future studies and developments of momilactone-based Anticancer medicines.