Glyoxalase I (GLO I), a major enzyme involved in the detoxification of the anaerobic glycolytic byproduct methylglyoxal, is highly expressed in various tumors, and is regarded as a promising target for cancer therapy. We recently reported that piceatannol potently inhibits human GLO I and induces the death of GLO I-dependent cancer cells. Pyruvate kinase M2 (PKM2) is also a potential therapeutic target for cancer treatment, so we evaluated the combined anticancer efficacy of piceatannol plus low-dose shikonin, a potent and specific plant-derived PKM2 inhibitor, in two GLO I-dependent cancer cell lines, HL-60 human myeloid leukemia cells and NCI-H522 human non-small-cell lung cancer cells. Combined treatment with piceatannol and low-dose shikonin for 48 h synergistically reduced cell viability, enhanced apoptosis rate, and increased extracellular methylglyoxal accumulation compared to single-agent treatment, but did not alter PKM1, PKM2, or GLO I protein expression. Taken together, these results indicate that concomitant use of low-dose shikonin potentiates piceatannol-induced apoptosis of GLO I-dependent cancer cells by augmenting methylglyoxal accumulation.

中文翻译：

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PKM2 抑制剂紫草素增强白皮杉醇诱导的乙二醛酶 I 依赖性癌细胞凋亡

乙二醛酶 I (GLO I) 是一种参与无氧糖酵解副产物甲基乙二醛解毒的主要酶，在多种肿瘤中高表达，被认为是癌症治疗的有希望的靶点。我们最近报道白皮杉醇可有效抑制人 GLO I 并诱导 GLO I 依赖性癌细胞死亡。丙酮酸激酶 M2 (PKM2) 也是癌症治疗的潜在治疗靶点，因此我们评估了白皮杉醇加低剂量紫草素（一种有效且特异性的植物源 PKM2 抑制剂）在两种 GLO I 依赖性癌细胞系中的联合抗癌功效、HL-60人髓性白血病细胞和NCI-H522人非小细胞肺癌细胞。与单药治疗相比，白皮杉醇和低剂量紫草素联合治疗 48 h 可协同降低细胞活力、提高细胞凋亡率并增加细胞外甲基乙二醛积累，但不会改变 PKM1、PKM2 或 GLO I 蛋白表达。综上所述，这些结果表明，同时使用低剂量紫草素可通过增加甲基乙二醛的积累，增强白皮杉醇诱导的 GLO I 依赖性癌细胞凋亡。