Ethanol extract of Patrinia scabiosaefolia induces the death of human renal cell carcinoma 786-O cells via SIRT-1 and mTOR signaling-mediated metabolic disruptions

Abstract

Recently, natural plant extracts have shown tremendous potential as novel antitumor drugs. Patrinia scabiosaefolia, a traditional prescription for inflammatory diseases, has been reported to effectively suppress various types of cancers. However, the mechanisms underlying its antitumor properties remain elusive. In the present study, we investigated the antitumor effects of an ethanol extract of Patrinia scabiosaefolia (EPS) on human renal cell carcinoma 786-O cells. After 24 h of incubation with EPS, the cell viability and colony number of 786-O cells were significantly decreased in a concentration-dependent manner as compared to the control group as determined by MTT and colony formation assays, respectively. The necrotic rate and apoptotic rate in the EPS exposure group were significantly higher than these rates noted in the control group as revealed by LDH release assay and Hoechst 33342/ PI double staining, respectively. At the concentration of 1.0 mg/ml, the necrotic and apoptotic rates reached 41.7±6.6 and 7.8±1.4%, respectively (P<0.01). However, the fluorescence intensity of intracellular calcium concentration ([Ca2+]i) was markedly elevated from 0.029±0.0007 to 0.060±0.003 (P<0.001) after the intervention of EPS. Moreover, the fluorescence intensity of intracellular ROS in the EPS exposure group was significantly higher (0.074±0.005) compared to that observed in the control group (0.033±0.001, P<0.001), which was partly attenuated by the specific antioxidant N-acetylcysteine (NAC). Furthermore, our results demonstrated that EPS significantly downregulated the expression of SIRT-1 and obviously induced the dephosphorylation of mTOR. Moreover, combined treatment with the SIRT-1 inhibitor nicotinamide and EPS was able to significantly enhance the induction of necrosis and reduction in cell viability of 786-O cells noted following treatment with EPS alone. In summary, we conclude that EPS induced the death of 786-O cells via SIRT-1 and mTOR signaling-mediated metabolic disruptions, which provide novel insight into the application of natural plant extracts for the treatment of cancers.

The Herba Patriniae (Caprifoliaceae): A review on traditional uses, phytochemistry, pharmacology and quality control

“…At the dose of 0.6 or 1 mg/mL, it markedly increased the levels of intracellular ROS and Ca 2+ , and significantly down-regulated the expression of SIRT-1 and reduced the ratio of pmTOR/mTOR. PS Li et al (2018) CRC mouse xenograft model (negative control: saline), HT-29 (negative control: culture solution) ethanol extract (500 g PS was extracted by refluxing with 5000 mL 85% ethanol and filtered. The ethanol solvent was concentrated by rotary evaporation to a relative density of 1.05.…”

“…In addition, it significantly inhibited SIRT-1 and mTOR signaling. Therefore, Li et al (2018) believed that the ethanol extract of PS induces the death of 786-O cells through metabolic disorders mediated by SIRT-1 and mTOR signaling. On the other hand, the studies on anti-cancer effect of ethanol extract of PV were relatively less.…”

Genomic and Transcriptome Analysis to Identify the Role of the mTOR Pathway in Kidney Renal Clear Cell Carcinoma and Its Potential Therapeutic Significance

“…The analysis of the transcriptomes of TCGA KIRC patients showed that there is a strong correlation between abnormal sirtuin and HDAC expression levels and the mTOR pathway. A recent study found that the ethanol extract of Patrinia scabiosaefolia induces the death of human renal cell carcinoma 786-O cells via SIRT1 and mTOR signaling-mediated metabolic disruptions [ 52 ]. SIRT5-mediated SDHA desuccinylation promotes clear cell renal cell carcinoma tumorigenesis [ 53 ].…”

MicroRNA-153-5p promotes the proliferation and metastasis of renal cell carcinoma via direct targeting of AGO1

“…Western blotting was performed as described previously 48,49 . Cells were lysed using RIPA buffer with Phenylmethanesulfonyl fluoride and phosphatase inhibitors, and total proteins were extracted after transfection.…”