Analgesic-antitumor peptide inhibits the migration and invasion of HepG2 cells by an upregulated VGSC β1 subunit

Abstract

Analgesic-antitumor peptide (AGAP), one of the scorpion toxin polypeptides, has been shown to have an antitumor activity. Recombinant AGAP (rAGAP) was shown to affect the migration and invasion of HepG2 cells via a voltage-gated sodium channel (VGSC) β1 subunit. The VGSC β1 subunit was validated as a cell adhesion molecule (CAM) in human hepatocellular carcinoma (HCC) cell lines. rAGAP suppresses the migration and invasion of HepG2 cells but has no significant effect of human liver HL7702 cells without β1 subunit expression. rAGAP inhibits the migration and invasion of the cells when the VGSC β1 subunit is overexpressed in HL7702 cells. To explain these findings, VGSC β1 subunit messenger RNA (mRNA) and protein levels were measured. The β1 subunit protein level was upregulated in a dose-dependent manner following treatment with rAGAP while there was no significant change in the mRNA level, so rAGAP might be an active component of the VGSC β1 subunit.

Scorpion Venom Analgesic Peptide, BmK AGAP Inhibits Stemness, and Epithelial-Mesenchymal Transition by Down-Regulating PTX3 in Breast Cancer

“…Studies have reported that BmK AGAP inhibited proliferation, migration and induced apoptosis in SW480 and SHG-44 cancer cells (40, 44). It was also reported that the analgesic peptide inhibited the migration and invasion of HepG2 cells (45). In the present study, we employed MCF-7, a differentiated breast cancer cell line that express estrogen receptor, and MDA-MB-231, a poorly differentiated triple- negative breast cancer cell line, as models and found that the scorpion analgesic peptide BmK AGAP, could effectively inhibit breast cancer cell stemness and epithelial-mesenchymal transition both in vitro and in vivo .…”

“…Zhao et al reported that BmK AGAP inhibits Nav 1.5 in SHG-14 cells and down-regulates p-AKT, pp-38, p-Erk1/2, and p-c-Jun, which gradually decreased the expression of NF-κB (40). Guo et al also reported that the analgesic peptide up-regulated the VGSC β1 subunit to inhibit migration and invasion of HepG2 cells (45). In this present study, the role of rBmK AGAP on the expression of Nav 1.5, PTX3, and TNF-α as well as NF-κB signal transduction, were further investigated to illustrate the potential molecular mechanism.…”

Monitoring the Early Antiproliferative Effect of the Analgesic–Antitumor Peptide, BmK AGAP on Breast Cancer Using Intravoxel Incoherent Motion With a Reduced Distribution of Four b-Values

“…Many studies reported some physiological effects of the Chinese scorpion BmK venom known for its antiepileptic, analgesic, and, recently, antitumor properties. The use of this Chinese scorpion BmK venom revealed apoptogenic, immunosuppressive, and antiproliferative properties and demonstrated the potential of the cocktail for cancer-related diseases (Zhao et al, 2011; Li et al, 2014; Al-Asmari et al, 2016, 2018; Guo et al, 2016; Liu et al, 2017). The antitumor effect of the BmK venom was later accredited to an analgesic peptide called BmK AGAP and others (Zhao et al, 2011; Guo et al, 2016).…”

Voltage‐gated sodium channels β3 subunit promotes tumorigenesis in hepatocellular carcinoma by facilitating p53 degradation

“…VGSCs are aberrantly expressed in tumors and play an important role in tumor growth and metastasis . β1 subunit has been reported in carcinoma cell lines derived from breast cancer , cervical cancer , and hepatocellular carcinoma , and it has a role in tumor growth and metastasis. β2 in prostate cancer cells increases adhesion, process outgrowth, migration, and invasion .…”