101. Molecular characterization of the antineoplastic effect of curcumin on acute myeloid leukemia cell lines

Aly Abdelkareem

Victoria Tomaz

Victoria Tomaz holds a degree in biomedicine and specializes in Hematology and Bioinformatics applied to Medical Genomics. She completed her master’s degree at the Graduate Program in Health Sciences at Hospital Israelita Albert Einstein and is currently a PhD student at the same institution. She also works as a visiting professor at the postgraduate courses in Molecular Biology at the São Paulo Institute of Research and Health Education (IPESSP) and Multiprofessional Oncology at Hospital Israelita Albert Einstein.

Abstract

Victoria Tomaz, Paulo Campregher

Hospital Israelita Albert Einstein, São Paulo, Brazil

Acute myeloid leukemia (AML), the most common myeloid neoplasm in adults is associated with high mortality if not adequately treated. Due to its great biological and genetic heterogeneity and the advanced age of most affected patients, it becomes increasingly difficult to treat the disease with chemotherapy or bone marrow transplantation. Thus, the search for new treatments with anti-leukemic activity and less toxicity is necessary. There is evidence in the literature that curcumin, a phenolic pigment extracted from plants from the Curcuma longa species, in addition to having anti-inflammatory benefits, has anti-neoplastic effects on various tumor types, including leukemias. To evaluate the antileukemic effect of curcumin on leukemic cell lines and identify genes and pathways associated with cytotoxicity. The leukemic cell lines HL-60, THP-1, OCI-AML2 and OCI-AML3 were treated with curcumin at different concentrations, and evaluated for cell death and cell cycle changes by means of flow cytometry based assays. Pre- and post-treatment samples were used for RNA extraction, transcriptome sequencing and subsequent WGCNA and GDE analyses. Curcumin causes variable degrees of cell death (sub-G0 phase of the cell cycle) at various concentrations. Whole transcriptome analysis revealed that curcumin treatment induced an increase in the expression of genes associated with the proteasome, cell cycle, TNF and NF-KB pathways. Curcumin causes cell death in AML cell lines and this cytotoxic effect is associated with the overexpression of genes associated with proteasome, cell cycle, TNF pathway. These results may contribute to the generation of new hypotheses regarding the anti-leukemogenic action of curcumin.