Potential interactions of Alpha Mangostin with Doxorubicin as potential Kinase inhibitors on myeloid leukaemic cell line

Leukaemia is a blood cancer with mutations of tyrosine kinases which are signalling molecules involoved in nearly every cancer. There are two types of leukemia myeloid and lymphoid leukaemia, each of which can be identified as acute such as acute myeloid leukaemia (AML) and chronic such as 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. The aim of this study is to investigate in vitro, the effect of phytochemicals, α-mangostin, gallic acid and ascorbic acid, singly and in combination with doxorubicin (DOX) as potential kinase inhibitors in AML cell line MOLM13. A range of concentrations (1 to 50 µM) of the above-mentioned phytochemicals were used to treat MOLM13 for 72 h with or without DOX (1 µM). CyQuant proliferation assay was used to determine the effect of the test compounds on cell viability. Apoptosis and cell cycle analysis were also conducted using a flow cytometer. Statistical analysis including ANOVA, Student T test were chosen for comparing the effects from different treatments. Results showed that α mangostin at concentration (≥20 µM) and two other compounds, gallic acid and ascorbic acid (≥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 combination study. Further studies to explore the mechanism of the effects from the combination study are on the way. Our findings may provide relevant information in identifying potential kinase inhibitors in treating AML