1. The Effects of Frondoside A in Acute Leukemia
- Author
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Thomas E. Adrian, Basil Ramadi, Milos Lijubisavijevic, Sajwani, Fatma Hussain, Thomas E. Adrian, Basil Ramadi, Milos Lijubisavijevic, and Sajwani, Fatma Hussain
- Abstract
Among hematological malignancies, acute leukemia is the major cause of mortality. Despite improvement of survival with current chemotherapies, some patients still diefrom the disease or the treatment side effects. Thus, new therapeutic agents are needed. Anti-cancer drugs derived from natural products are of interest. Frondoside A is a triterpenoid glycoside form the sea cucumber, Cucumaria frondosa that has shown potent antitumor effects in various cancers. Previous studies in acute leukemia are limited. The current study investigated the effects of frondoside a in acute leukemia cell lines alone and in combination with drugs currently used for this malignancy. This study is the first to attempt comparing the efficacy of this compound to available conventional drugs. The acute leukemia cell lines used were CCRF-CEM, HL-60 and THP-1. Cells were cultured and treated with different concentrations of frondoside A, vincristine sulphate, asparaginase and prednisolone each compound alone and in combination with frondoside A. Experiments were conducted with treatment incubation periods of 24, 48 and 72h. The inhibitory concentration 50 (IC50) for each compound at each time point was determined for the three cell lines using the CellTiter-Glo luminescence assay. Induction of apoptosis was examined using Annexin V test and expression of apoptosis-related genes (low-density expression array) was investigated in two acute leukemia cell lines. The expression of protein products of selected genes was also investigated. The effect of frondoside A combined with NFκB pathway inhibitor, andrographolide in acute leukemia cell lines was also examined. CCRF-CEM cells were very sensitive to frondoside a treatment while HL-60 and THP-1 were less sensitive. Frondoside A markedly enhanced the anticancer effects of all of the conventional drugs in all cell lines. Synergistic effects were seen in some of the combination concentrations. Induction of apopto
- Published
- 2017