Doxorubicin combined with phytochemicals as pro-apototic agents and potential protein kinase inhibitors for the treatment of Acute Myeloid Leukaemia


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Uzoma Cynthia Osemeke1
1Middlesex University

Abstract

Background

Leukaemia is a blood cancer with mutations of tyrosine kinases which are signalling molecules involoved in nearly every cancer. Leukemia is classified as myeloid or lymphoid leukaemia, each of which can be identified as acute leukaemia such as the acute myeloid leukaemia (AML) or chronic leukaemia such as the chronic myeloid leukaemia (CML) depending on the developing process. Kinases are crucial in controling metabolism, cell division, transcription and programmed cell death. Mutations in tyrosine kinases are well known to relate with cancer development and progression. A tyrosine kinase inhibitor, imatinib (Gleevec ST1571), has been successfully used in treating CML by selectively targeting genetically altered tyrosine kinase. However, due to the complexity and the high frequency of the mutations identified in AML, the success rates from commonly used tyrosine kinase inhibitors are low in comparison of CML. Phytochemicals for this study were selected after critical literature review. The aim of this study is to investigate in vitro, the effect of phytochemicals, α-mangostin, gallic acid and vitamin C, singly and in combination with doxorubicin (DOX) as pro-apoptotic agents and potential protein kinase inhibitors in AML cell line MOLM13.

Method

CyQuant proliferation assay was used to determine the effect of the test compounds on cell viability. Apoptosis and cell cycle assays were also conducted using a flow cytometer.

Results

Results showed that α mangostin at concentration (≥20 µM) and two other compounds, gallic acid and vitamin C (≥15 µM) inhibited cell growth in a dose dependent manner. More apoptotic effects were observed when they were combined with Dox (1 µM). G2/M phase cell cycle arrest was induced by all combinations studied.

Conclusion

Further studies to explore the mechanism of effect by the combinations studied are on the way. Our findings may provide relevant information on potential kinase inhibitors in treating AML.