You Fang-Fang, Zhang Jing, Cheng Fan, Zou Kun, Zhang Xue-Qing, Chen Jian-Feng
Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China.
Int J Mol Sci. 2021 Nov 14;22(22):12302. doi: 10.3390/ijms222212302.
RCE-4, a steroidal saponin isolated from , has been studied previously and has exhibited promising anti-cervical cancer properties by inducing programmed cell death (PCD) of Ca Ski cells. Considering the cancer cells developed various pathways to evade chemotherapy-induced PCD, there is, therefore, an urgent need to further explore the potential mechanisms underlying its actions. The present study focused on targeting the Bcl-2-Beclin 1 complex, which is known as the key regulator of PCD, to deeply elucidate the molecular mechanism of RCE-4 against cervical cancer. The effects of RCE-4 on the Bcl-2-Beclin 1 complex were investigated by using the co-immunoprecipitation assay. In addition, autophagy-related genes (ATG) were also analyzed due to their special roles in PCD. The results demonstrated that RCE-4 inhibited the formation of the Bcl-2-Beclin 1 complex in Ca Ski cells via various pathways, and ATG 4B proteins involved in this process served as a key co-factor. Furthermore, based on the above, the sensitivity of RCE-4 to Ca Ski cells was significantly enhanced by inhibiting the expression of the ATG 4B by applying the ATG 4B siRNA plasmid.
RCE - 4是一种从[具体来源未给出]中分离出的甾体皂苷，此前已被研究，并且通过诱导Ca Ski细胞的程序性细胞死亡（PCD）展现出了有前景的抗宫颈癌特性。鉴于癌细胞会发展出各种途径来逃避化疗诱导的PCD，因此，迫切需要进一步探索其作用的潜在机制。本研究聚焦于靶向Bcl - 2 - Beclin 1复合物（已知为PCD的关键调节因子），以深入阐明RCE - 4抗宫颈癌的分子机制。通过免疫共沉淀试验研究了RCE - 4对Bcl - 2 - Beclin 1复合物的影响。此外，由于自噬相关基因（ATG）在PCD中的特殊作用，也对其进行了分析。结果表明，RCE - 4通过多种途径抑制Ca Ski细胞中Bcl - 2 - Beclin 1复合物的形成，参与此过程的ATG 4B蛋白作为关键辅助因子。此外，基于上述结果，通过应用ATG 4B siRNA质粒抑制ATG 4B的表达，显著增强了RCE - 4对Ca Ski细胞的敏感性。
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