tretinoin and Squamous-Cell-Carcinoma-of-Head-and-Neck

Topics: Animals; B7-H1 Antigen; Carcinoma, Squamous Cell; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Mice; Mice, Inbred C3H; Mouth Neoplasms; Nanoparticles; Polyethylene Glycols; Squamous Cell Carcinoma of Head and Neck; Tretinoin; Tumor Microenvironment

There are limited studies on the effects of drugs that modulate epigenetic regulation for head and neck squamous cell carcinoma (HNSCC). This study determined the effect of valproic acid (VPA) on HNSCC.. Growth inhibition effects of VPA alone or in combination with 5-aza-2'deoxycytidine (5-aza-dC) or all-trans retinoic acid (ATRA) was evaluated with MTT and clonogenic assays on 5 HNSCC cell lines. The mechanism of growth inhibition was investigated by looking at markers of terminal differentiation and senescence.. Growth inhibition profiles of HNSCC cell lines varied in response to VPA. Inhibition of clonogenic survival in response to VPA was associated with an upregulation of p21, expression of terminal differentiation markers, and cellular senescence. Notably, a combination treatment of 5-Aza-dC-VPA-ATRA enhanced growth inhibition in cells resistant to VPA.. VPA is a potent inhibitor of proliferation in some HNSCC cell lines, and may be used to treat HNSCC.

Topics: Antineoplastic Agents; Azacitidine; Carcinoma, Squamous Cell; Cell Culture Techniques; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Cellular Senescence; Decitabine; Head and Neck Neoplasms; Histone Deacetylase Inhibitors; Humans; Squamous Cell Carcinoma of Head and Neck; Tretinoin; Valproic Acid

Differentiation therapy is a novel approach to eradicate cancer stem cells (CSCs), including head and neck squamous carcinoma CSC (HNSC CSC). All-trans-retinoic acid (ATRA) is a potent differentiating agent. We studied the anti-tumour effect of ATRA on HNSC CSC. HNSC CSCs were differentiated by ATRA in a serum-free conditioned medium. The effect of differentiation on tumour growth was assessed in vitro and in vivo, and chemosensitisation was examined using a colorimetric viability assay. In addition, the involvement of Wnt/β-catenin signalling as an underlying mechanism of the anti-tumour effect of retinoic acid (RA) on HNSC CSCs was assessed. ATRA suppressed the expression of the stem cell markers Oct4, Sox2, Nestin and CD44 in HNSC CSCs and inhibited the proliferation of HNSC CSCs in vitro and in vivo. Furthermore, ATRA treatment augmented the chemosensitising effects of cisplatin. The anti-tumour effects of ATRA may be associated with down-regulation of Wnt/β-catenin signalling. In conclusion, ATRA may be potentially valuable in treatment of HNSC CSC, especially in combination with cisplatin.

Topics: Animals; Antineoplastic Agents; beta Catenin; Carcinoma, Squamous Cell; Cell Proliferation; Cisplatin; Female; Head and Neck Neoplasms; Humans; Mice; Mice, Inbred BALB C; Neoplastic Stem Cells; Squamous Cell Carcinoma of Head and Neck; Tretinoin; Wnt Signaling Pathway