Key result
Oleanolic acid plus CAV-1 overexpression increases HL-60 cell apoptosis ~7-fold via PI3K/AKT/mTOR inhibition.
CAV-1 plays a crucial role in mediating the anti-leukemic effects of oleanolic acid in HL-60 cells by inhibiting the PI3K/AKT/mTOR signaling pathway.
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Reduced CAV-1 in leukemia cells may reflect tumor biology; hypothesis-generating and requires clinical validation before any therapeutic consideration.
Our previous study found that caveolin-1 (CAV-1) protein expression is upregulated during oleanolic acid (OA)-induced inhibition of proliferation and promotion of apoptosis in HL-60 cells. CAV-1 is the main structural protein component of caveolae, playing important roles in tumorigenesis and tumor development. It has been shown that cav-1 expression is lower in leukemia cancer cell lines SUP-B15, HL-60, THP-1 and K562 and in chronic lymphocytic leukemia primary (CLP) cells when compared with normal white blood cells, with the lowest cav-1 expression level found in HL-60 cells. To study the effects of cav-1 in HL-60 cells and the effects of cav-1 overexpression on OA drug efficacy, cav-1 was overexpressed in HL-60 cells using lentiviral-mediated transfection combined with OA treatment. The results showed that cav-1 overexpression inhibited HL-60 cell proliferation, promoted apoptosis, arrested the cell cycle in the G1 phase and inhibited activation of the PI3K/AKT/mTOR signaling pathway. Overexpression of CAV-1 also increased HL-60 cell sensitivity to OA. To further verify whether OA affects HL-60 cells via the activation of downstream signaling pathways by CAV-1, cav-1 gene expression was silenced using RNAi, and the cells were treated with OA to examine its efficacy. The results showed that after cav-1 silencing, OA had little effect on cell activity, apoptosis, the cell cycle and phosphorylation of HL-60 cells. This study is the first to show that CAV-1 plays a crucial role in the effects of OA on HL-60 cells.
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Ma et al. (2014) studied Acute myelogenous leukemia (AML). Oleanolic acid (OA) and CAV-1 overexpression vs. Untreated HL-60 cells was evaluated on Apoptosis rate at 24 hours (p=<0.01). Oleanolic acid combined with CAV-1 overexpression significantly promoted HL-60 cell apoptosis (41.19% vs 5.79% in control) and inhibited the PI3K/AKT/mTOR signaling pathway.
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