Abstract
Purpose: To investigate the anti-proliferative potential of quinolinol-platinum (II) complex {QN-Pt (II)} in laryngeal cancer cells.Methods: The inhibitory potential of QN-Pt (II) on the proliferation of laryngeal cancer cells was determined using 2H-tetrazolium, 2-(4,5-dimethyl-2-thiazolyl)-3,5-diphenyl bromide (MTT) and colony formation assays. Inhibition of cell migration was determined using wound-healing assay, while changes in LC3-II and p62 expressions were assessed by western blotting.Results: QN-Pt (II) inhibited the viability of TU212 and M4e laryngeal cancer cells in the concentration range of 2 to 10 μM (p < 0.05). Moreover, it suppressed the colony formation potential and migration of TU212 and M4e cells. The QN-Pt (II) treatment increased the proportion of TU212 and M4e cells in G1/G0 phase of the cell cycle, but decreased the cell proportion in S and G2/M phase (p < 0.05). Treatment with 10 μM QN-Pt (II) increased the expression of LC3-II, but downregulated P62 expression in TU212 and M4e cells. The expression of Yes-associated protein was inhibited in TU212 and M4e cells on treatment with QN-Pt (II). However, transfection of YAP-cDNA into TU212 and M4e cells reversed the inhibitory effect of QN-Pt (II) on cell proliferation (p < 0.05). Moreover, YAP-cDNA transfection suppressed LC3II expression, inhibited YAP phosphorylation and promoted P62 expression in QN-Pt (II)-treated TU212 and M4e cells (p < 0.05).Conclusion: QN-Pt (II) suppresses laryngeal cancer cell viability via arrest of cell cycle and activation of apoptosis. Moreover, QN-Pt (II) targets Yes-associated protein in laryngeal cancer cells. Thus, QN-Pt (II) is a potential therapeutic agent for laryngeal cancer.
 Keywords: Laryngeal cancer, YAP-protein, Apoptosis, Phosphorylation, Therapeutic agent
Highlights
Laryngeal cancer comprises squamous cell carcinomas which originate from the skin of the larynx [1]
Treatment of TU212 and M4e cancer cells with QN-Pt (II) in the concentration range of 1-10 μM suppressed their viability without affecting normal HBe cells (Figure 1 A)
The colony-forming potential of TU212 and M4e cells were reduced on treatment with QN-Pt (II), when compared to control (Figure 1 C)
Summary
Laryngeal cancer comprises squamous cell carcinomas which originate from the skin of the larynx [1]. The TU212, M4e and HBe cells were seeded in 96-well plates at a density of 2 x 105 cells per well, and cultured for 24 h. The cells were seeded in 6-well plates at a density of 1 x 105 cells per well, and treated with 8 and 10 μM QN-Pt (II) for 48 h. They were stained with crystal violet dye (Beyotime Institute) for 45 min at room temperature, and the stained cells were observed under optical light microscope (IX70; Olympus Corporation) for colony formation. The scratched cells were cleared by washing the dishes with PBS to remove any cell debris This was followed by addition of serumfree medium. The cells were separately treated with 8 or 10 μM QN-Pt (II) for 48 h
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