Abstract
Spider venom has been found to show its anticancer activity in a variety of human malignancies, including lung cancer. In this study, we investigated the anti-cancer peptide toxin LVTX-8, with linear amphipathic alpha-helical conformation, designed and synthesized from the cDNA library of spider Lycosa vittata. Multiple cellular methods, such as CCK-8 assay, flow cytometry, colony formation assay, Transwell invasion and migration assay, were performed to detect peptide-induced cell growth inhibition and anti-metastasis in lung cancer cells. Our results demonstrated that LVTX-8 displayed strong cytotoxicity and anti-metastasis towards lung cancer in vitro. Furthermore, LVTX-8 could suppress the growth and metastasis of lung cancer cells (A549 and H460) in nude mouse models. Transcriptomics, integrated with multiple bioinformatics analysis, suggested that the molecular basis of the LVTX-8-mediated inhibition of cancer cell growth and metastasis manifested in two aspects: Firstly, it could restrain the activity of cancer cell division and migration through the functional pathways, including “p53 hypoxia pathway” and “integrin signaling”. Secondly, it could regulate the expression level of apoptotic-related proteins, which may account for programmed apoptosis of cancer cells. Taken together, as an anticancer peptide with high efficiency and acceptable specificity, LVTX-8 may become a potential precursor of a therapeutic agent for lung cancer in the future.
Highlights
Lung cancer is the leading cause of cancer-related mortality worldwide [1]
LVTX-8 could impair cell invasion ability in both cell models in a dose-dependent manner (Figure 3B,D). These results clearly demonstrated that LVTX-8 inhibited cancer cell growth, and possessed an anti-metastasis function in lung cancer cells at a concentration below the IC50
Some peptides derived from spider venom are potential candidates for anti-cancer therapy, including lung cancer
Summary
Lung cancer is the leading cause of cancer-related mortality worldwide [1]. The prognosis of lung cancer is poor and always misleading, due to the deficiency of symptoms in the early stage [2].The development of distant metastases accompanied by generalized symptoms in multiple organsToxins 2020, 12, 367; doi:10.3390/toxins12060367 www.mdpi.com/journal/toxinsToxins 2020, 12, 367 is the final stage of lung cancer progression [3]. The prognosis of lung cancer is poor and always misleading, due to the deficiency of symptoms in the early stage [2]. There is an urgent need to search for new therapeutic agents for lung cancer therapy. From spiders, insects, snakes and scorpions, is a valuable source for the development of anti-cancer drugs [4,5,6,7]. Multiple spider venom components show potential therapeutic activity against cancer, including lung cancer [8,9,10]. Naturally occurring anticancer peptides (ACPs), and the corresponding information of sequence structure, provide significant references for the creation of new ACPs in therapeutic applications [11,12]. Multiple bioinformatics tools and combinatorial libraries have been used for the de novo minimalist design of amphipathic peptides, and template modifications can benefit the identification of new ACP sequences [13,14]
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