双去甲氧基姜黄素通过 CYLD 介导的去泛素化作用抑制 Akt 失活从而抑制肝癌增殖。
Bisdemethoxycurcumin Inhibits Hepatocellular Carcinoma Proliferation Through Akt Inactivation via CYLD-Mediated Deubiquitination.
机构信息
Department of Abdominal Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, People's Republic of China.
Department of Breast Surgery, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People's Republic of China.
出版信息
Drug Des Devel Ther. 2020 Mar 5;14:993-1001. doi: 10.2147/DDDT.S231814. eCollection 2020.
BACKGROUND
Bisdemethoxycurcumin (BDMC), a stable bioactive ingredient in curcuminoids, is associated with various antitumor functions, such as proliferation inhibition, metastasis suppression and apoptosis induction, in many cancer types. However, the mechanism of BDMC in hepatocellular carcinoma (HCC) remains unclear.
METHODS
We assessed the toxicity and the inhibitory effect of BDMC in the HepG2 cell line by using CCK-8 and colony formation assays. The regulatory effects of BDMC on Akt and MAPK signaling were investigated by Western blotting and immunoprecipitation.
RESULTS
We found that the half-maximum inhibitory concentration (IC50) of BDMC after 48 hrs of treatment was 59.13 μM, and BDMC inhibited proliferation in a time- and dose-dependent manner in HepG2 cells. The inhibitory effect was caused by the inactivation of Akt signaling, but not Erk, Jnk or p38 signaling. In addition, the inactivation of Akt signaling was attributed to the inhibition of ubiquitination mediated by K63-Ub but not K48-Ub. Furthermore, we found that BDMC upregulated the expression of CYLD, leading to Akt deubiquitination and inactivation.
CONCLUSION
BDMC inhibited HCC cell proliferation, and that this effect was induced by Akt inactivation via CYLD-mediated deubiquitination.
背景
双去甲氧基姜黄素（BDMC）是姜黄素类中的一种稳定生物活性成分，与多种肿瘤类型中的增殖抑制、转移抑制和凋亡诱导等多种抗肿瘤功能相关。然而，BDMC 在肝细胞癌（HCC）中的作用机制尚不清楚。
方法
我们通过 CCK-8 和集落形成实验评估了 BDMC 在 HepG2 细胞系中的毒性和抑制作用。通过 Western blot 和免疫沉淀实验研究了 BDMC 对 Akt 和 MAPK 信号通路的调节作用。
结果
我们发现，BDMC 在 48 小时处理后的半最大抑制浓度（IC50）为 59.13 μM，BDMC 可时间和剂量依赖性地抑制 HepG2 细胞的增殖。这种抑制作用是由 Akt 信号通路的失活引起的，而不是 Erk、Jnk 或 p38 信号通路。此外，Akt 信号通路的失活归因于 K63-Ub 介导的而不是 K48-Ub 介导的泛素化抑制。此外，我们发现 BDMC 上调了 CYLD 的表达，导致 Akt 去泛素化和失活。
结论
BDMC 抑制 HCC 细胞增殖，这种作用是通过 CYLD 介导的去泛素化使 Akt 失活诱导的。
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