鬼臼毒素可浓度依赖地拆散 XIAP 与半胱天冬酶-9 复合物：《科学报告》以分裂荧光素酶定量检测验证、11 月 11 日刊出
《科学报告》2026 年 11 月 11 日刊出 Katrin Ebrahimi、Farangis Ataei 与 Saman Hosseinkhani 的研究，考察植物来源木脂素鬼臼毒素如何作用于细胞凋亡通路。鬼臼毒素具有强抗癌性质，研究假设其能模拟 Smac 的活性，与凋亡抑制蛋白的 BIR 结构域相互作用。
研究团队开发并验证了一套高灵敏、无细胞的分裂荧光素酶互补检测系统，用来实时定量 XIAP 的 BIR2 至 BIR3 结构域与其关键靶标半胱天冬酶-3 和半胱天冬酶-9 之间的相互作用动态。结果显示，BIR2 至 BIR3 与半胱天冬酶-9 的相互作用明显比与半胱天冬酶-3 的相互作用更稳固、更稳定，提示在起始型半胱天冬酶层面存在优先结合机制。
利用该平台，团队检验了鬼臼毒素对这一相互作用的调控。与计算机对接预测一致，鬼臼毒素以浓度依赖方式拆散 XIAP 与半胱天冬酶-9 的复合物，使发光信号明显下降，并随后恢复半胱天冬酶-9 的酶活性。鬼臼毒素对 XIAP 与半胱天冬酶-3 相互作用只有轻微抑制，对半胱天冬酶-9 轴的影响明显更强。
对照方面，DNA 交联剂卡铂对这些蛋白相互作用没有显著影响，证实了所观察到的鬼臼毒素效应的特异性。作者表示，这些发现建立了一个灵敏、实时的 XIAP 与半胱天冬酶轴监测平台，并提供了有力证据，表明鬼臼毒素是凋亡通路的靶向调节剂，值得作为药理学制剂进一步开发。本稿以论文摘要为准。
Podophyllotoxin Disrupts the XIAP and Caspase-9 Complex in a Concentration-Dependent Manner: Scientific Reports Study Validated with a Quantitative Split-Luciferase Assay, Published November 11
Scientific Reports published a study by Katrin Ebrahimi, Farangis Ataei and Saman Hosseinkhani on November 11, 2026, examining how the plant-derived lignan podophyllotoxin acts on the apoptosis pathway. Podophyllotoxin has potent anticancer properties, and the study hypothesized that it mimics Smac activity by interacting with the BIR domains of inhibitor of apoptosis proteins.
The team developed and validated a highly sensitive, cell-free split-luciferase complementation assay designed to quantify the real-time interaction dynamics between the BIR2 to BIR3 domains of XIAP and its key targets, caspase-3 and caspase-9. The results demonstrate that the interaction with caspase-9 is significantly more robust and stable than the interaction with caspase-3, highlighting a preferential binding mechanism at the initiator caspase level.
Using this platform, the team investigated the effects of podophyllotoxin in modulating the interaction. Consistent with in silico docking predictions, podophyllotoxin disrupted the XIAP and caspase-9 complex in a concentration-dependent manner, leading to a marked reduction in luminescence and a subsequent restoration of caspase-9 enzymatic activity. Podophyllotoxin showed a minor inhibitory effect on the XIAP and caspase-3 interaction, while its impact on the caspase-9 axis was markedly more pronounced.
Carboplatin, a DNA-crosslinking agent, exhibited no significant impact on these protein-protein interactions, confirming the specificity of the observed podophyllotoxin effects. The authors state that the findings establish a sensitive, real-time platform for monitoring the XIAP and caspase axis and provide compelling evidence that podophyllotoxin acts as a targeted modulator of the apoptotic pathway, warranting its further development as a pharmacological agent. This report follows the abstract of the paper.
来源：《科学报告》
发布：GSM·美国（发布链接）
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