Praeruptorin B Mitigates the Metastatic Ability of Human Renal Carcinoma Cells through Targeting CTSC and CTSV Expression.

Chia-Liang Lin,Chien-Min Chen,Tsung-Ho Ying,Tung-Wei Hung,Chi-Jui Lin,Yi-Hsien Hsieh

doi:10.3390/ijms21082919

Abstract

Renal cell carcinoma (RCC) is the most common adult kidney cancer, and accounts for 85% of all cases of kidney cancers worldwide. Praeruptorin B (Pra-B) is a bioactive constituent of Peucedanum praeruptorum Dunn and exhibits several pharmacological activities, including potent antitumor effects. However, the anti-RCC effects of Pra-B and their underlying mechanisms are unclear; therefore, we explored the effects of Pra-B on RCC cells in this study. We found that Pra-B nonsignificantly influenced the cell viability of human RCC cell lines 786-O and ACHN at a dose of less than 30 μM for 24 h treatment. Further study revealed that Pra-B potently inhibited the migration and invasion of 786-O and ACHN cells, as well as downregulated the mRNA and protein expression of cathepsin C (CTSC) and cathepsin V (CTSV) of 786-O and ACHN cells. Mechanistically, Pra-B also reduced the protein levels of phospho (p)-epidermal growth factor receptor (EGFR), p-mitogen-activated protein kinase kinase (MEK), and p-extracellular signal-regulated kinases (ERK) in RCC cells. In addition, Pra-B treatment inhibited the effect of EGF on the upregulation of EGFR–MEK–ERK, CTSC and CTSV expression, cellular migration, and invasion of 786-O cells. Our findings are the first to demonstrate that Pra-B can reduce the migration and invasion ability of human RCC cells through suppressing the EGFR-MEK-ERK signaling pathway and subsequently downregulating CTSC and CTSV. This evidence suggests that Pra-B can be developed as an effective antimetastatic agent for the treatment of RCC.

Highlights

Kidney cancer accounts for approximately 3% of adult malignancies, and yearly kidney cancer incidence rates are increasing in more developed regions of the world [1]
Our results demonstrated that Praeruptorin B (Pra-B) suppressed cellular motility through reducing the mRNA and protein expression of cathepsin C (CTSC)/cathepsin V (CTSV) and suppressing the epidermal growth factor receptor (EGFR)–mitogen-activated protein kinase kinase (MEK)–extracellular signal-regulated kinases (ERK) signaling pathway
These results demonstrated that Pra-B has an inhibitory effect on 786-O and ACHN cell migration and invasion capacities

Summary

Introduction

Kidney cancer accounts for approximately 3% of adult malignancies, and yearly kidney cancer incidence rates are increasing in more developed regions of the world [1]. Many studies have indicated that angular-type pyranocoumarins and furanocoumarins are major constituents of dried roots of P. praeruptorum [4], and pharmacological studies have shown that these compounds may possess a wide variety of activities, such as anti-inflammatory [5], antiasthma [6], and neuroprotective [7]. Praeruptorin A (Pra-A) is reported to exert a protective effect on osteoporosis through inhibiting the p38/AKT/c-Fos/NAFTc1 pathway [8]. Pra-C was observed to mitigate cardiac damage and have a clear effect on blood pressure in spontaneously hypertensive rats, suggesting its potential as a novel drug for the treatment and prevention of cardiovascular diseases [9]. Another study demonstrated that praeruptorins enhanced the sensitivity of doxorubicin, paclitaxel, and vincristine in cancer cells [12], suggesting a potential anticancer effect. The effects and molecular mechanisms of the antitumor effect of Pra-B on RCC have far not been clarified

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Conclusion