Bae Jaehoon, Park Su-Jin
Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Republic of Korea.
Curr Issues Mol Biol. 2024 Mar 14;46(3):2444-2455. doi: 10.3390/cimb46030154.
Diallyl disulfide (DADS) is a well-known principal functional component derived from garlic () that has various health benefits. Previously, we identified a 67-kDa laminin receptor, a receptor for oolong tea polyphenol oolonghomobisflavan B (OHBFB). However, its molecular mechanisms still remain to be elucidated. Here, we show that DADS synergistically enhanced the effect of the oolong tea polyphenol oolonghomobisflavan B (OHBFB), which induces apoptosis in acute myeloid leukemia (AML) cancer cells without affecting normal human peripheral blood mononuclear cells (PBMCs). The underlying mechanism of OHBFB-induced anti-AML effects involves the upregulation of the 67-kDa laminin receptor/endothelial nitric oxide synthase/cyclic guanosine monophosphate (cGMP)/protein kinase c delta (PKCδ)/acid sphingomyelinase (ASM)/cleaved caspase-3 signaling pathway. In conclusion, we show that the combination of OHBFB and DADS synergistically induced apoptotic cell death in AML cells through activation of 67LR/cGMP/PKCδ/ASM signaling pathway. Moreover, in this mechanism, we demonstrate DADS may reduce the enzyme activity of phosphodiesterase, which is a negative regulator of cGMP that potentiates OHBFB-induced AML apoptotic cell death without affecting normal PBMCs.
二烯丙基二硫醚（DADS）是一种源自大蒜的著名主要功能成分，具有多种健康益处。此前，我们鉴定出一种67 kDa的层粘连蛋白受体，它是乌龙茶多酚乌龙同型双黄酮B（OHBFB）的受体。然而，其分子机制仍有待阐明。在此，我们表明DADS协同增强了乌龙茶多酚乌龙同型双黄酮B（OHBFB）的作用，后者可诱导急性髓系白血病（AML）癌细胞凋亡，而不影响正常人外周血单个核细胞（PBMC）。OHBFB诱导抗AML作用的潜在机制涉及上调67 kDa层粘连蛋白受体/内皮型一氧化氮合酶/环磷酸鸟苷（cGMP）/蛋白激酶cδ（PKCδ）/酸性鞘磷脂酶（ASM）/裂解的半胱天冬酶-3信号通路。总之，我们表明OHBFB和DADS的组合通过激活67LR/cGMP/PKCδ/ASM信号通路协同诱导AML细胞凋亡性细胞死亡。此外，在这一机制中，我们证明DADS可能降低磷酸二酯酶的酶活性，磷酸二酯酶是cGMP的负调节因子，可增强OHBFB诱导的AML凋亡性细胞死亡，而不影响正常PBMC。
