Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu 41062, Korea.
School of Korean Medicine, Dongguk University, Gyeongju 38066, Korea.
Biomolecules. 2021 Dec 1;11(12):1806. doi: 10.3390/biom11121806.
Chemotherapy is an essential strategy for cancer treatment. On the other hand, consistent exposure to chemotherapeutic drugs induces chemo-resistance in cancer cells through a variety of mechanisms. Therefore, it is important to develop a new drug inhibiting chemo-resistance. Although hemistepsin A (HsA) is known to have anti-tumor effects, the molecular mechanisms of HsA-mediated cell death are unclear. Accordingly, this study examined whether HsA could induce apoptosis in aggressive prostate cancer cells, along with its underlying mechanism. Using HsA on two prostate cancer cell lines, PC-3 and LNCaP cells, the cell analysis and in vivo xenograft model were assayed. In this study, HsA induced apoptosis and autophagy in PC-3 cells. HsA-mediated ROS production attenuated HsA-induced apoptosis and autophagy after treatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. Moreover, autophagy inhibition by 3-MA or CQ is involved in accelerating the apoptosis induced by HsA. Furthermore, we showed the anti-tumor effects of HsA in mice, as assessed by the reduced growth of the xenografted tumors. In conclusion, HsA induced apoptosis and ROS generation, which were blocked by protective autophagy signaling.
化疗是癌症治疗的重要策略。另一方面，持续接触化疗药物通过多种机制诱导癌细胞产生化疗耐药性。因此，开发一种新的抑制化疗耐药性的药物非常重要。尽管半 stepsin A（HsA）已知具有抗肿瘤作用，但 HsA 介导的细胞死亡的分子机制尚不清楚。因此，本研究探讨了 HsA 是否可以诱导侵袭性前列腺癌细胞凋亡及其潜在机制。使用 HsA 对两种前列腺癌细胞系 PC-3 和 LNCaP 细胞进行细胞分析和体内异种移植模型检测。在这项研究中，HsA 诱导 PC-3 细胞凋亡和自噬。HsA 介导的 ROS 产生减弱了 N-乙酰-L-半胱氨酸（NAC）处理后 HsA 诱导的凋亡和自噬，NAC 是一种 ROS 清除剂。此外，3-MA 或 CQ 抑制自噬可加速 HsA 诱导的凋亡。此外，我们在小鼠中显示了 HsA 的抗肿瘤作用，通过减少异种移植肿瘤的生长来评估。总之，HsA 诱导了凋亡和 ROS 的产生，而保护性自噬信号阻断了这一过程。
