The effects of thymoquinone and Doxorubicin on leukemia and cardiomyocyte cell lines.

Acute Lymphoblastic Leukemia remains the most common cancer for children, and if left untreated is rapidly fatal. The gold standard for treatment of ALL in children is with a class of drugs known as the antracyclines. Long term outcomes following treatment of leukemia with antracylines can result in cardiac abnormalities including arrhythmias, congestive heart failure, myocardial infarction, hypertension and left ventricular failure. Thymoquinone is a natural product that has demonstrated anti-proliferative, anti-inflammatory, anti-cancer, and chemo-protective effects in control trials as well as a reduction in cardiotoxicity in antracyline treated rats. The aims of the study were to determine if thymoqunione could be used to reduce leukemia cell viability without injuring primary cardiomyocyte, and to determine its effects if used in conjunction with a known chemotherapeutic agent. Cellular viability and morphological changes were observed in the, RAW leukemia cells and cardiac myocytes following treatment with thymoquinone, antracyline (doxorubicin), alone and in combination for 24, 48 and 72 hours. The results suggest that thymoquinone treatment in RAW leukemia cells reduced the cell number without altering the morphology, while doxorubicin reduced cell number and induced spindle cell formation and increased cellular damage. Findings also suggest RAW cell apoptosis increased in combination therapy with thymoquinone and doxorubicin. Thymoquinone administered to cardiomyocytes showed similar morphological changes as control over time in culture; whereas doxorubicin treated cells showed evidence of loss of connectivity and disruption of cell membranes. Combination treatment with doxorubicin and thymoquinone demonstrated significant cardiac myocyte survival at concentrations when used alone were able to reduce the leukemia cells. Overall, the data is promising and may provide a treatment regime to protect the heart tissue. Additional work is warrant to understand the mechanisms involved to reduce cardio toxicity by combining thymoquinone with doxorubicin.