Among five major anthocyanin compounds, delphinidin exhibited the most potent and selective cytocidal effect against HL-60, a trivalent arsenic (As(III))-resistant cell line. Co-treatment with delphinidin and As(III) resulted in the reduction of IC₅₀ value for As(III) from 11.2 to 1.5 μM, which was considered as clinically achieved concentrations of As(III). The combination treatment strongly preferred to selectively enhance the cytotoxicity of As(III) against HL-60 cells rather than human peripheral blood mononuclear cells. The induction of apoptosis as evidenced by the increase of sub-G₁ cells, DNA fragmentation, annexin V-positive cells and the activation of caspase-8, -9 and -3 was observed in HL-60 cells co-treated with As(III) and delphinidin. Similar to the activation pattern of caspases, a substantial decrease in the expression level of Bid along with the loss of mitochondrial membrane potential was also observed. These results suggested that the combination treatment triggered a convergence of the intrinsic and extrinsic pathways of apoptosis via the activation of caspase-8 and cleaved Bid. Delphinidin itself significantly decreased the intracellular GSH ([i]GSH) and nuclear factor-κB (NF-κB) binding activity, and further returned As(III)-triggered increment of [i]GSH and enhancement of NF-κB binding activity to control level. Additionally, buthionine sulfoximine, a GSH depletor; JSH-23, a NF-κB inhibitor, also mimicked the capacity of delphinidin to significantly induce the reduction of [i]GSH along with the potentiation of As(III) cytotoxicity in HL-60 cells. These observations suggested that delphinidin-induced sensitization of HL-60 cells to As(III) was caused by the reduction of [i]GSH, which was probably associated with the inhibitory effect of delphinidin on NF-κB binding activity. These findings further suggest that delphinidin-induced sensitization of HL-60 cells to As(III) may lead to dose reduction of As(III) in clinical application, and ultimately contribute to minimizing its side effects.

在五种主要的花色苷化合物中，飞燕草素对HL-60（一种具有三价砷（As（III））耐药性的细胞系）HL-60表现出最强效和选择性的杀细胞作用。与delphinidin和As（III）共同处理导致As（III）的IC ₅₀值从11.2降至1.5μM，这被认为是临床上达到的As（III）浓度。联合治疗强烈优选选择性地增强As（III）对HL-60细胞而非人外周血单核细胞的细胞毒性。sub-G ₁的增加证明了细胞凋亡的诱导在用As（III）和delphinidin共处理的HL-60细胞中观察到了细胞，DNA片段化，膜联蛋白V阳性细胞以及caspase-8，-9和-3的激活。与半胱天冬酶的激活模式相似，还观察到Bid表达水平的显着下降以及线粒体膜电位的丧失。这些结果表明，联合治疗通过激活caspase-8和裂解的Bid触发了凋亡的内在和外在途径的融合。Delphinidin本身显着降低了细胞内GSH（[i] GSH）和核因子-κB（NF-κB）的结合活性，并使Asi（III）触发的[i] GSH增量增加，并使NF-κB结合活性增强。控制级别。此外，丁硫氨酸亚砜亚胺（一种GSH消耗剂）；NF-κB抑制剂JSH-23，还模拟了delphinidin显着诱导[i] GSH降低以及在HL-60细胞中增强As（III）细胞毒性的能力。这些观察结果表明，delphiinidin诱导的HL-60细胞对As（III）的敏化是由[i] GSH的降低引起的，这可能与delphinidin对NF-κB结合活性的抑制作用有关。这些发现进一步表明，在临床应用中，delphinidin诱导的HL-60细胞对As（III）的致敏作用可能导致As（III）的剂量减少，并最终有助于最大程度地降低其副作用。这些观察结果表明，delphiinidin诱导的HL-60细胞对As（III）的敏化是由[i] GSH的降低引起的，这可能与delphinidin对NF-κB结合活性的抑制作用有关。这些发现进一步表明，在临床应用中，delphinidin诱导的HL-60细胞对As（III）的致敏作用可能导致As（III）的剂量减少，并最终有助于最大程度地降低其副作用。这些观察结果表明，delphiinidin诱导的HL-60细胞对As（III）的敏化是由[i] GSH的降低引起的，这可能与delphinidin对NF-κB结合活性的抑制作用有关。这些发现进一步表明，在临床应用中，delphinidin诱导的HL-60细胞对As（III）的致敏作用可能导致As（III）的剂量减少，并最终有助于最大程度地降低其副作用。