PTC+ COMPOUND PRESENT CYTOTOXIC EFFECTS AND REDUCES AURKB GENE EXPRESSION IN ACUTE MYELOID LEUKEMIA CELLS (KG-1).

INTRODUCTION AND OBJECTIVE: Alterations in cell cycle control lead to uncontrolled proliferation, invasion, and metastasis, key features of cancer. In leukemia and other oncohematologic diseases, abnormal differentiation during hematopoietic progenitor and stem cell division drives disease progression. Cell cycle-specific chemotherapeutic agents regulate cell division and effectively target proliferating cancer cells. Natural pterocarpans, derived from Platymiscium floribundum, have important biological activities such as antifungal, antibacterial, insecticidal and remarkable antitumour activity with cytotoxic effects against several tumour cell lines in vitro. Similarly, synthetic pterocarpan (PTC+) shows promising antitumour potential in previous studies by our group. We sought to evaluate the cytotoxic profile of PTC+ against leukemia cell lines and its impact on the cell cycle control and the expression of related. MATERIALS AND METHODS: The antiproliferative activity of PTC+ was assessed by MTT assay. Membrane integrity and cell cycle analysis were conducted by flow cytometry. Gene expression analysis was conducted by quantitative PCR using TaqMan probes. RESULTS AND CONCLUSION: PTC+ showed antiproliferative effects in all leukemia cell lines tested. The IC₅₀ values ranged from 0.41µM ± 0.13 in HL-60 to 7.51µM± 0.29 in K-562 cell line. The HL-60 (IC₅₀ = 0.41µM ± 0.13) and KG-1 (IC₅₀ = 1.0µM ± 0.09) cell lines showed the highest sensitivity compared to non-tumour cells (PBMC). PTC+ resulted in changes in membrane integrity at 24 and 48 hours (24.58% and 37.57%, respectively), and induced G2/M phase arrest at 12, 24 and 48 hours of treatment (p<0.001). Morphological changes were observed in KG-1, including increased vacuolization, decreased nuclear content, and plasma membrane blebs. Gene expression of CEP55, MAD2, CDC20 and ATM did not change after 12 and 24 hours of incubation. AURKB expression was reduced after 24 hours of treatment (p<0.02) with PTC+. PTC+ exhibits both antiproliferative and cytotoxic effects in acute myeloid leukemia cell through G2/M cell cycle arrest and reduction of AURKB expression. This is consistent with other studies highlighting its impact at this phase of cell cycle. Aurora kinases are critical for chromosome alignment, mitotic spindle formation, and cytokinesis, making AURKB a significant target in anticancer therapy.