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

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.

Phytochemicals for the Prevention and Treatment of Renal Cell Carcinoma: Preclinical and Clinical Evidence and Molecular Mechanisms

“…Praeruptorin B (Figure 2), a naturally derived compound found in Peucedanum praeruptorum, Saposhnikovia divaricata, and Angelica cincta plants commonly used in Chinese medicine, is known to exhibit potent antitumor properties [176]. Praeruptorin B displayed cytotoxic effects against 786-O and ACHN RCC cell lines as observed by Lin et al [177]. Praeruptorin B was found to potently inhibit migration and invasion of the RCC cells, as evidenced by decreased production of cathepsin C (CTSC) and cathepsin V (CTSV) proteins, proteases that regulate cancer cell invasion extracellularly.…”

Construction and Validation of a Necroptosis-Related Signature Associated With the Immune Microenvironment in Liver Hepatocellular Carcinoma

“…Musculin antisense RNA 1 (MSC-AS1) is a lncRNA, which interacts largely with miRNAs and acts as an oncogene in several cancers ( Li et al, 2021 ; Liu et al, 2021 ; Ma et al, 2021 ; Zhao et al, 2021 ). Cathepsin V (CTSV/CTSL2) is a proteolytic enzyme that degrades the extracellular matrix promoting tumor metastasis and invasion ( Lin et al, 2020 ; Toss et al, 2020 ; Wang et al, 2020 ). Bone morphogenetic protein 6 (BMP6) is involved in growth, differentiation, and apoptosis and is an important regulator of tumors and the tumor microenvironment ( Liu et al, 2014 ; Seo et al, 2019 ; Stieglitz et al, 2019 ; García Muro et al, 2021 ).…”

A Review on Anomalin: A Natural Bioactive Pyranocoumarin from the Past to the Future

“…[91] Pyranocoumarins are also an important group of coumarins with their biological activities, as antiinflammatory, chemoprotective, anticancer, anti-asthma, neuroprotective, anti-HIV effects. [31,[92][93][94][95] The angular-type dihydropyranocoumarins with ester groups at positions C-3' and C-4' might have hopeful therapeutic potential as anti-inflammatory agents. [96] Khellactones also exhibited spasmolytic action, and the most popular ones as visnadin, dihydrosamidin, pteryxin have found implementation in the treatment of some cardiovascular diseases, as well as suksdorfin and samidin [60] Tetracycline pyranocoumarins show significantly anti-HIV activity.…”

“…Pyranocoumarins are also an important group of coumarins with their biological activities, as anti‐inflammatory, chemoprotective, anticancer, anti‐asthma, neuroprotective, anti‐HIV effects [31,92–95] . The angular‐type dihydropyranocoumarins with ester groups at positions C‐3′ and C‐4′ might have hopeful therapeutic potential as anti‐inflammatory agents [96] .…”