[PMID]: | 29381751 |
[Au] Autor: | Chea C; Miyauchi M; Inubushi T; Febriyanti Ayuningtyas N; Subarnbhesaj A; Nguyen PT; Shrestha M; Haing S; Ohta K; Takata T |
[Ad] Endereço: | Department of Oral & Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. |
[Ti] Título: | Molecular mechanism of inhibitory effects of bovine lactoferrin on the growth of oral squamous cell carcinoma. |
[So] Source: | PLoS One;13(1):e0191683, 2018. |
[Is] ISSN: | 1932-6203 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | BACKGROUND: Lactoferrin (LF), a member of the transferrin family, recently has been demonstrated to have anticancer effects on various cancers including oral squamous cell carcinoma (OSCC). However, little is known about the underlying mechanisms of its effects on OSCC. Therefore, we aimed to investigate the mechanism of the suppressive effects of bovine LF (bLF) on the growth of OSCC cells. METHODS: In the current study, HSC2, HSC3, HSC4 and normal human oral keratinocytes (RT7) cell lines were tested with bLF 1, 10, and 100 µg/ml. The effects and detail mechanisms of bLF on proliferation and apoptosis of cells were investigated using flow cytometry and western blotting. RESULTS: We found that bLF (1, 10, and 100 µg/ml) induced activation of p53, a tumor suppressor gene, is associated with the induction of cell cycle arrest in G1/S phase and apoptosis in OSCC. Moreover, bLF downregulated the phosphorylation of Akt and activated suppressor of cytokine signaling 3 (SOCS3), thereby attenuating multiple signaling pathways including mTOR/S6K and JAK/STAT3. Interestingly, we revealed that bLF exerted its effect selectively against HSC3 but not on RT7 via different effects on the phosphorylation status of NF-κB and Akt. CONCLUSION: This is the first report showing that bLF selectively suppresses proliferation through mTOR/S6K and JAK/STAT3 pathways and induction of apoptosis in OSCC. This study provides important new findings, which might be useful in the prevention and treatment of OSCC. |
[Mh] Termos MeSH primário: |
Carcinoma de Células Escamosas/patologia Lactoferrina/farmacologia Neoplasias Bucais/patologia
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[Mh] Termos MeSH secundário: |
Animais Bovinos Ciclo Celular/efeitos dos fármacos Linhagem Celular Transformada Proliferação Celular/efeitos dos fármacos Seres Humanos
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| EC 3.4.21.- (Lactoferrin) |
[Em] Mês de entrada: | 1803 |
[Cu] Atualização por classe: | 180309 |
[Lr] Data última revisão:
| 180309 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 180131 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1371/journal.pone.0191683 |
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