CASTICIN: A PROMISING CANDIDATE TO DEVELOP A STEM CELL TARGETED STRATEGY IN AML TREATMENT

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Erkmen T.

3rd International Cancer and Ion Channels Congress, İstanbul, Turkey, 16 - 18 October 2021, pp.47, (Summary Text)

  • Publication Type: Conference Paper / Summary Text
  • City: İstanbul
  • Country: Turkey
  • Page Numbers: pp.47
  • Erzincan Binali Yildirim University Affiliated: No

Abstract

Purpose: Acute myeloid leukemia is the most common form of acute leukemia with genetic and epigenetic heterogeneity. Although current chemotherapeutics provide successful remission, 5-year survival rates are still low. Insufficiency of targeting leukemia stem cells is considered as the main obstacle that cause drug resistance and relapse. Phytochemicals, especially polyphenols remain a promising source for targeted drug research. Studies showed that Casticin, which is a predominant polyphenolic component of the fruit of Vitex trifolia, has antiproliferative effects on leukemic cells, but its effects on leukemic stem cells are still unclear. In this study, we aimed to investigate the antiproliferative capacity of Casticin on acute myeloid leukemia stem-like (KG1a) cell line and its parental (KG1) cell line comparison with healthy peripheral blood mononuclear (PBMC) cell line.

Method: The antiproliferative effects of Casticin on cells and IC50 values were determined by MTT test. The effects of Casticin on caspase 3/7 activity, apoptosis, and necrosis in cells were evaluated by flow cytometry and TUNEL assays.

Results: 2 μM Casticin treatment for 24 h was increased apoptosis, caspase 3/7 activation in KG1 (27,2%; 17,30%; p<0,01), KG1a (21,6%; 11,35%; p<0,01) with relatively low necrosis (1,4%; 0,3%) compared to their control groups. TUNEL assay also confirmed Casticin-induced apoptosis in KG1 (22,3%; p<0,05), KG1a cells (19,03%; p<0,05). There were no significant changes in apoptosis (10,6%), caspase 3/7 activity (0,24%), necrosis (0,6%) of PBMC compared to its control group.

Conclusion: Casticin has the capacity to induce apoptosis in both leukemia stem-like and parental cells without significantly affecting healthy cells. Therefore, we think that Casticin can be a promising compound to develop novel therapeutic strategies for final AML treatment.