Abstract
BackgroundGlabridin, a prenylated isoflavonoid of G. glabra L. roots, has been associated with a wide range of biological properties such as regulation of energy metabolism, estrogenic, neuroprotective, anti-osteoporotic, and skin-whitening in previous studies. However, the effect of glabridin on tumor cells metastasis has not been clearly clarified. Here, the molecular mechanism by which glabridin anticancer effects in human promyelocytic leukemia cells was investigated.Methodology and Principal FindingsThe results showed that glabridin significantly inhibited cell proliferation of four AML cell lines (HL-60, MV4-11, U937, and THP-1). Furthermore, glabridin induced apoptosis of HL-60 cells through caspases-3, -8, and -9 activations and PARP cleavage in dose- and time-dependent manner. Moreover, western blot analysis also showed that glabridin increase phosphorylation of ERK1/2, p38 MAPK and JNK1/2 in dose- and time-dependent manner. Inhibition of p38 MAPK and JNK1/2 by specific inhibitors significantly abolished the glabridin-induced activation of the caspase-3, -8 and -9.ConclusionTaken together, our results suggest that glabridin induced HL-60 cell apoptosis through p38 MAPK and JNK1/2 pathways and could serve as a potential additional chemotherapeutic agent for treating AML.
Highlights
Occurring plant products have gained increasing attention for potential use in intervention against malignant invasive progression in late stage neoplastic diseases [1,2]
Taken together, our results suggest that glabridin induced HL-60 cell apoptosis through p38 MAPK and JNK1/2 pathways and could serve as a potential additional chemotherapeutic agent for treating Acute myeloid leukemia (AML)
To determine whether the inhibitory effect of cell viability of glabridin is associated with induction of cell apoptosis, HL-60 and MV4-11 cells were treated with different concentrations (0– 40 mM) of glabridin for 24 h
Summary
Occurring plant products have gained increasing attention for potential use in intervention against malignant invasive progression in late stage neoplastic diseases [1,2]. This product is part of a larger family of plantderived molecules, the natural phenols. Glabridin have shown positive effects in fields like LDL protection against oxidation and anti-obesity could potentially provide benefits to human health [5,6,7]. The effects of glabridin on human promyelocytic leukemia have yet to be evaluated. A prenylated isoflavonoid of G. glabra L. roots, has been associated with a wide range of biological properties such as regulation of energy metabolism, estrogenic, neuroprotective, anti-osteoporotic, and skin-whitening in previous studies. The molecular mechanism by which glabridin anticancer effects in human promyelocytic leukemia cells was investigated
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