Abstract
Shikonin mitigated tumor cell proliferation by elevating reactive oxygen species (ROS) levels. Herein, we investigated the effects of shikonin on renal cancer cell (RCC) cell proliferation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that shikonin dose-dependently reduced the proliferation of Caki-1 and ACHN cells. Shikonin remarkably triggered necrosis and apoptosis in Caki-1 and ACHN cells in proportion to its concentration. Moreover, necrostatin-1 recovered cell viability in the presence of shikonin. Elevated ROS levels and mitochondrial dysfunction were also found in shikonin treatment groups. Pretreatment with N-acetyl cysteine remarkably mitigated shikonin-induced cell death and ROS generation. Western blot analysis revealed that shikonin reduced pro-PARP, pro-caspase-3, and Bcl-2 expression and increased cleavage PARP expression. Enhanced autophagy was also found in the shikonin-treated group as evidenced by acridine orange staining. Moreover, light chain 3B (LC3B)-II accumulation and enhanced p62 expression indicated that autophagy occurred in the shikonin-treated group. LC3B knockdown considerably recovered cell viability in the presence of shikonin. Shikonin treatment elevated p38 activity in a dose-dependent manner. In conclusion, our results revealed that shikonin triggered programmed cell death via the elevation of ROS level and p38 activity in different types of RCC cells. These findings suggested that shikonin may be a potential anti-RCC agent.
Highlights
Renal cell carcinoma (RCC) is a highly prevalent cancer all over the world and one of the top 10 cancers in the United States [1]
Shikonin Mitigated Cell Proliferation of Renal Cancer Cell (RCC) through Induction of assay was conducted to assess the effects of shikonin on renal cancer cell (RCC) cell proliferat
Cell viability decreased to 62.1%, 39.8%, and 39.5% in ACHN cells and 51.9%, 49.1%, MTT assay was conducted to assess the effects of shikonin on RCC cell proliferation
Summary
Renal cell carcinoma (RCC) is a highly prevalent cancer all over the world and one of the top 10 cancers in the United States [1]. RCC can be divided into clear cell carcinoma (75–80%), papillary carcinoma (~15%), and chromophobe carcinoma (~5%) according to histopathological characteristics [2]. Searching for more effective drugs for RCC is an urgent issue. Shikonin mitigates cell proliferation in various types of human cancer cell lines [4]. Shikonin remarkably elevated the percentage of necroptosis in glioma C6 and U87 MG cells in a dose-dependent manner, and this effect was diminished by necrostatin-1 (necroptosis inhibitor) [5]. Shikonin promoted cell death in triple-negative breast cancer MDA-MB-231 cells through the regulation of inosine 50-monophosphate dehydrogenase 2 [6].
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