Abstract
BackgroundLactoferrin (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.MethodsIn 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.ResultsWe 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.ConclusionThis 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.
Highlights
Anti-cancer drugs derived from natural compounds are highly safe for the treatment of cancers
We found that bovine LF (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 oral squamous cell carcinoma (OSCC)
BLF downregulated the phosphorylation of Akt and activated suppressor of cytokine signaling 3 (SOCS3), thereby attenuating multiple signaling pathways including mammalian target of rapamycin (mTOR)/S6 kinase (S6K) and JAK/STAT3
Summary
Anti-cancer drugs derived from natural compounds are highly safe for the treatment of cancers. Lactoferrin (LF), an 80-kDa member of the transferrin family of iron binding glycoproteins [1], is naturally produced by epithelial cells [2] and found in external secretions mainly in milk [3]. For many years, LF and its derivatives have been proposed for cancer therapy due to their multiple tumor-targeting and high cytological effects on cancer cells [11,12,13]. Inhibition of cell cycle progression in cancer cells is one of the main mechanisms by which LF may inhibit cancer growth. 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). We aimed to investigate the mechanism of the suppressive effects of bovine LF (bLF) on the growth of OSCC cells
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