Human Beta-Defensin-1, -2, and -3 Exhibit Opposite Effects on Oral Squamous Cell Carcinoma Cell Proliferation

Winter, Jochen; Pantelis, A.; Reich, Rudolf; Martini, M.; Kraus, Dominik; Jepsen, Soeren; Allam, Jean‐Pierre; Novak, Natalija; Wenghoefer, Matthias

doi:10.3109/07357907.2010.543210

Cited by 60 publications

(63 citation statements)

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“…The inconsistency between our findings compared to those from previous investigations reporting that tumors overexpressing hBD3 or Defb14 showed enhanced solidtumor growth remains unclear (14,15,27). This may have occurred because of differences in the concentration of hBD3 and Defb14 used, although the concentration of 20 μg/ml defensin used in our study was not excessively higher than that at which antimicrobial activity was observed (10).…”

Section: Figure 3 Time Dependency Of Cellular Damage Induced By Humacontrasting

confidence: 56%

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In Vitro and In Vivo Anticancer Activity of Human β-Defensin-3 and Its Mouse Homolog

Hanaoka

Yamaguchi

Yamamoto

et al. 2016

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Abstract. Background Antimicrobial peptides have emerged as a part of the host defense mechanism in both animals and plants (1, 2). Specifically, defensins and cathelicidins are antimicrobial peptides found in humans (3). In the defensin family, there are α-defensin and β-defensin subfamilies, which conserve three specific disulfide pairings. These are produced by leukocytes and various types of epithelial cells constitutively, or in response to microbial signals and inflammatory cytokines (4-6).Human β-defensin-3 (hBD3) was first isolated from human skin (7) and its expression was detected in many tissues, including airway epithelial cells (8,9). In contrast to other defensin isoforms, the prominent features of hBD3 antimicrobial activity are its salt-independency and its broad antimicrobial spectrum (7, 10, 11).While antimicrobial peptides have attracted attention as potential molecules to treat cancer (12), previous observations on the anticancer effects of hBD3 have not been consistent. Some studies hypothesized that hBD3 can be oncogenic because hBD3 is frequently overexpressed in oral squamous cell carcinomas (13-15). Winter et al. indicated that hBD3 inhibited colon cancer-cell migration, although not cell proliferation (16). Moreover, Phan et al. indicated that hBD3 exhibits anticancer effects on various tumor cells through cell permeabilization (17).Here, we investigated the anticancer activities of various isoforms of β-defensin on lung cancer cells, and confirmed that this anticancer activity is also seen in animal models of cancer. Materials and MethodsReagents. Synthetic hBD1, hBD2, hBD3 and human neutrophil peptide-1 (HNP1) peptides were purchased from the PEPTIDE institute (Minoh, Japan), and were dissolved in 0.001% acetic acid to give a final concentration of 2 mg/ml.We predicted the mature Defb14 peptide spanning 45 COOHterminal amino acids as a mouse homolog of hBD3, identical to the predicted mature peptide of Defb14 from a previous report (18). At the Peptide Institute (Minoh, Japan), we chemically synthesized mature Defb14 peptide (19,20). The synthetic peptide was airoxidized to form three disulfide bonds. The material was eluted as a 5999 *These Authors contributed equally to this study.Correspondence to: Yasuhiro Yamaguchi, Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. Tel: +81 358008652, Fax: +81 358006530, e-mail: yamayasu-tky@umin.ac.jp Key Words: Antimicrobial peptide, cytotoxicity, membrane damage. ANTICANCER RESEARCH 36: 5999-6004 (2016) single peak on reverse-phase high-performance liquid chromatography and confirmed by mass spectroscopy. It was lyophilized and dissolved in 0.001% acetic acid to give a final concentration of 2 mg/ml.Cell culture. A549 human lung carcinoma cells were obtained from the Cell Resource Center for Biomedical Research, Tohoku University (Sendai-shi, Japan). Lewis lung carcinoma (LLC) cells were obtained from RIKEN BRC (Tsukuba-shi, Japan). The cells were routine...

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Section: Figure 3 Time Dependency Of Cellular Damage Induced By Humacontrasting

confidence: 56%

“…Some studies hypothesized that hBD3 can be oncogenic because hBD3 is frequently overexpressed in oral squamous cell carcinomas (13)(14)(15). Winter et al indicated that hBD3 inhibited colon cancer-cell migration, although not cell proliferation (16).…”

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confidence: 99%

In Vitro and In Vivo Anticancer Activity of Human β-Defensin-3 and Its Mouse Homolog

Hanaoka

Yamaguchi

Yamamoto

et al. 2016

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“…Additionally, hBD-2 has a strong impact on the maturation of premature osteoblasts [15]. Furthermore, hBD-1, -2, and -3 have been demonstrated to stimulate the proliferation of tumor cells in vitro [16] (Figure 4). Apart from that, the gene products of human β-defensins cross-regulate their own gene expression [15,16].…”

Section: Tissue Reorganization and Wound Healingmentioning

confidence: 99%

“…Recently, it has been demonstrated that human β-defensins are involved in bisphosphonate-associated osteochemonecrosis of the jawbone [13]. Furthermore, these antimicrobial peptides are able to affect their own genes-either directly or indirectly by modulating gene activity and secretion of cytokines, which in consequence leads to feedback mechanisms on defensin genes [4,[14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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Human Defensins: Potential Tools for Clinical Applications

Winter

Wenghoefer

2012

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As components of the innate immune system, antimicrobial peptides in the form of human defensins play an important role in host defense by serving as the epithelial layer’s biochemical barrier against local infections. Recent studies have shown these molecules to have far more additional cellular functions besides their antimicrobial activity. Defensins play a role in cell division, attraction and maturation of immune cells, differentiation and reorganization of epithelial tissues, wound healing and tumor suppression. This multitude of function makes human defensins appear to be excellent tools for therapeutic approaches. These antimicrobial peptides may be used directly as a remedy against bacterial and viral infections. Furthermore, the application of human defensins can be used to promote wound healing and epithelial reorganization. In particular, human β-defensins have a strong impact on osteoblast proliferation and differentiation. Human β-defensins have already been applied as a vaccination against HIV-1. Another potentially useful characteristic of defensins is their suitability as diagnostic markers in cancer therapy. In particular, α-defensins have already been used for this purpose. Human α-defensin-3, for example, has been described as a tumor marker for lymphocytes. High gene expression levels of α-defensin-3 and -4 have been detected in benign oral neoplasia, α-defensin-6 is considered to be a tumor marker for colon cancer.

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Distinct pattern of chromosomal alterations and pathways in tongue and cheek squamous cell carcinoma

et al. 2013

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Background The purpose of this study was to investigate the cause of behavioral difference between tongue and cheek squamous cell carcinomas (SCCs) by verifying the copy number alterations (CNAs). Methods Array comparative genomic hybridization (aCGH) was used to profile unique deletions and amplifications that are involved with tongue and cheek SCC, respectively. This was followed by pathway analysis relating to CNA genes from both sites. Results The most frequently amplified regions in tongue SCC were 4p16.3, 11q13.4, and 13q34; whereas the most frequently deleted region was 19p12. For cheek SCC, the most frequently amplified region was identified on chromosome 9p24.1‐9p23; whereas the most common deleted region was located on chromosome 8p23.1. Further analysis revealed that the most significant unique pathway related to tongue and cheek SCCs was the cytoskeleton remodeling and immune response effect on the macrophage differentiation pathway. Conclusion This study has showed the different genetic profiles and biological pathways between tongue and cheek SCCs. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1268–1278, 2014

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Human Beta-Defensin-1, -2, and -3 Exhibit Opposite Effects on Oral Squamous Cell Carcinoma Cell Proliferation

Cited by 60 publications

References 19 publications

In Vitro and In Vivo Anticancer Activity of Human β-Defensin-3 and Its Mouse Homolog

In Vitro and In Vivo Anticancer Activity of Human β-Defensin-3 and Its Mouse Homolog

Human Defensins: Potential Tools for Clinical Applications

Distinct pattern of chromosomal alterations and pathways in tongue and cheek squamous cell carcinoma

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