Radiation Research Division, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeollabuk 56212, Republic of Korea.
Department of Radiological Science, Konyang University, Daejeon 35365, Republic of Korea.
Mol Med Rep. 2021 Jun;23(6). doi: 10.3892/mmr.2021.12064. Epub 2021 Apr 13.
Prednisolone is an anti‑inflammatory drug used to treat a number of conditions, including liver disease and cancer. Numerous studies have demonstrated that glucocorticoids such as prednisolone modified by ionizing radiation can promote anticancer activity in cancer cells. To the best of our knowledge, however, the effect of ionizing radiation on prednisolone structure and cancer cells has not yet been identified. The present study created a novel prednisolone derivative using γ‑irradiation, and its anticancer properties were investigated in liver cancer cells. The present study confirmed the structure of the new prednisolone derivative using liquid chromatogram‑mass spectrometry. MTT assays determined the cytotoxic effects of γ‑irradiated (IR)‑prednisolone in liver cancer cells. Flow cytometry analysis evaluated apoptosis, mitochondrial membrane potential and cell cycle distribution. Western blotting was used to analyze the proteins associated with apoptosis. The chromatogram profile revealed that IR‑prednisolone produced a number of peaks compared with the single peak of the original prednisolone. In contrast to prednisolone, the MTT results showed that IR‑prednisolone significantly prevented the growth of liver cancer cells. IR‑prednisolone promoted apoptosis and arrested the cell cycle at the G0/G1 stage in Huh7 cells. IR‑prednisolone also altered the mitochondrial membrane potential and activated caspase‑associated proteins, which activated the intrinsic apoptotic signaling pathway. In conclusion, IR‑prednisolone promoted anticancer effects in liver cancer cells via apoptosis activation. The present study demonstrated that IR‑prednisolone may be a potential anticancer agent against liver cancer, although specific molecules have yet to be identified.
泼尼松龙是一种用于治疗多种疾病的抗炎药物，包括肝病和癌症。许多研究表明，经过电离辐射修饰的糖皮质激素，如泼尼松龙，可以促进癌细胞的抗癌活性。然而，据我们所知，电离辐射对泼尼松龙结构和癌细胞的影响尚未确定。本研究使用γ-射线辐照创建了一种新型泼尼松龙衍生物，并在肝癌细胞中研究了其抗癌特性。本研究使用液相色谱-质谱联用技术确证了新型泼尼松龙衍生物的结构。MTT 分析测定了γ-辐照（IR）-泼尼松龙对肝癌细胞的细胞毒性作用。流式细胞术分析评估了细胞凋亡、线粒体膜电位和细胞周期分布。Western blot 用于分析与细胞凋亡相关的蛋白。色谱图显示，与原始泼尼松龙的单个峰相比，IR-泼尼松龙产生了多个峰。与泼尼松龙相比，MTT 结果表明，IR-泼尼松龙显著抑制了肝癌细胞的生长。IR-泼尼松龙在 Huh7 细胞中促进细胞凋亡并将细胞周期阻滞在 G0/G1 期。IR-泼尼松龙还改变了线粒体膜电位并激活了与半胱氨酸蛋白酶相关的蛋白，从而激活了内在凋亡信号通路。综上所述，IR-泼尼松龙通过激活细胞凋亡促进肝癌细胞的抗癌作用。本研究表明，IR-泼尼松龙可能是一种有潜力的肝癌治疗药物，尽管尚未确定具体的分子。
