Abstract
Oral squamous cell carcinoma is the fifth most common epithelial cancer in the world, and its current clinical treatment has both low efficiency and poor selectivity. Cationic amphipathic peptides have been proposed as new drugs for the treatment of different types of cancer. The main goal of the present work was to determine the potential of LfcinB(20–25)4, a tetrameric peptide based on the core sequence RRWQWR of bovine lactoferricin LfcinB(20–25), for the treatment of OSCC. In brief, OSCC was induced in the buccal pouch of hamsters by applying 7,12-Dimethylbenz(a)anthracene, and tumors were treated with one of the following peptides: LfcinB(20–25)4, LfcinB(20–25), or vehicle (control). Lesions were macroscopically evaluated every two days and both histological and serum IgG assessments were conducted after 5 weeks. The size of the tumors treated with LfcinB(20–25)4 and LfcinB(20–25) was smaller than that of the control group (46.16±4.41 and 33.92±2.74 mm3 versus 88.77±10.61 mm3, respectively). Also, LfcinB(20–25)4 caused acellularity in the parenchymal tumor compared with LfcinB(20–25) and vehicle treatments. Furthermore, our results demonstrated that both LfcinB(20–25)4 and LfcinB(20–25) induced higher degree of apoptosis relative to the untreated tumors (75–86% vs 8%, respectively). Moreover, although the lowest inflammatory response was achieved when LfcinB(20–25)4 was used, this peptide appeared to induce higher levels of IgG antibodies relative to the vehicle and LfcinB(20–25). In addition the cellular damage and selectivity of the LfcinB(20–25)4 peptide was evaluated in vitro. These assays showed that LfcinB(20–25)4 triggers a selective necrotic effect in the carcinoma cell line. Cumulatively, these data indicate that LfcinB(20–25)4 could be considered as a new therapeutic agent for the treatment of OSCC.
Highlights
Oral squamous cell carcinoma (OSCC), one of the ten most common cancers in the world, has a delayed clinical detection and poor prognosis [1]
Tetrameric peptide derived from bovine lactoferricin as treatment for oral squamous cell carcinoma a recipient of scholarships from COLCIENCIAS for doctorates in Colombia (Grant 511-2010)
Tetrameric peptide derived from bovine lactoferricin as treatment for oral squamous cell carcinoma and LfcinB(20–25)4 at 200 and 300 μg/mL were reduced and stiff, showing traits of necrosis in the tumor
Summary
Oral squamous cell carcinoma (OSCC), one of the ten most common cancers in the world, has a delayed clinical detection and poor prognosis [1]. Several studies have described their selectivity and cytotoxic activity in a wide range of tumors using different in vitro and in vivo cancer models [6,7,8,9,10] These studies indicate that CAPs are likely to trigger fewer side effects [11,12,13,14,15,16] as well as induce immunogenic cell death, which in turn prevents cancer recurrence [10, 17, 18] and represents a significant advance towards more efficient cancer treatments. Additional studies have revealed that the high content of cationic and hydrophobic amino acids in CAPs, such as arginine and tryptophan, are critical for their antitumoral selective activity [19] These peptides are prone to interaction with anionic cell membrane surfaces [20], which are characteristic of cancer cells: they have more anionic molecules on the surface than non-cancerous cells. Regarding CAPs, their anticancer mechanism of action is suggested to be the induction of cell necrosis (via cell membrane lysis) or cell apoptosis (via slight damage to the plasma membrane or the mitochondrial lytic effect), which depend on the peptide concentration [23, 24]
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