4′,7-Di-O-methylnaringenin (DMNG), a naringenin derivative, activates p53 signal pathway through down-regulating MDM2
4′,7-Di-O-methylnaringenin (DMNG), a naringenin derivative, activates p53 signal pathway through down-regulating MDM2
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DOI：
10.1016/j.jff.2022.104962
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发表时间：
2022-02
影响因子：
5.6
通讯作者：
Siyu Zhang;Yifan Wang;Yujie Sun;Guang-rui Zhao;Juan Wang;Lu Liu;F. Liu;Peng Wang;Ximing Xu
中科院分区：
文献类型：
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作者：
Siyu Zhang;Yifan Wang;Yujie Sun;Guang-rui Zhao;Juan Wang;Lu Liu;F. Liu;Peng Wang;Ximing Xu
柚皮素是一种具有多种生物活性的柑橘类黄酮，已成为一种潜在的治疗药物，用于治疗多种疾病，但柚皮素衍生物在癌症治疗中的应用及其作用机制尚未完全了解。近年来，我们的研究发现4′，7-二-O-甲基柚皮素（DMNG）具有抗结肠癌活性，并对其作用机制进行了初步探讨。我们报道DMNG可以激活p53信号通路，依赖于p53野生型状态。DMNG通过诱导HCT-116细胞凋亡和G2/M期阻滞，降低HCT-116细胞的存活率。我们进一步证明，在剂量和时间依赖性的方式，DMNG有效地下调MDM 2蛋白在蛋白质翻译水平的表达。因此，我们的研究发现，DMNG是一个潜在的治疗和抗转移剂，通过下调MDM 2和激活p53通路的人结肠癌。
Naringenin, a citrus flavonoid that possessed various biological activities, had emerged as a potential therapeutic agent for the management of a variety of diseases, but naringenin derivatives’ application in cancer therapy and underlying mechanisms of action were not fully understood. Our recent work had shown that 4′,7-Di-O-methylnaringenin (DMNG) exerted its anti-colon cancer activity and the underlying mechanisms of action. We reported that DMNG could activate p53 signal pathway, dependent of p53 wild type status. We observed that DMNG decreased the survival of HCT-116 cells by induction of apoptosis and G2/M phase arrest. We further demonstrated that, in a dose- and time-dependent manner, DMNG effectively downregulated the MDM2 protein expression at protein translation level. Hence, our study unearthed that DMNG was a potential therapeutic and anti-metastatic agent for human colon cancer through down-regulating MDM2 and activating p53 pathway.