p-hydroxycinnamaldehyde and Head-and-Neck-Neoplasms

Few studies have examined the effect of 2'-hydroxycinnamaldehyde (HCA) on head and neck squamous cell carcinoma (HNSCC) cell invasion. This study examined the role of BMP7 on the anti-migration and anti-invasion activity of HCA using HNSCC cells.. Matrigel invasion and wound healing assays were conducted to investigate cell migration or invasion. BMP7 overexpression vector or siRNA mixture was used for transient regulation of gene expression.. HCA attenuated HNSCC cell migration and spheroids Matrigel invasion without cytotoxicity. mRNA and protein expression of BMP7 increased with HCA treatment. Exogenous BMP7 overexpression without HCA treatment attenuated Matrigel invasion of cells. Furthermore, suppression of BMP7 by siRNA alleviated the inhibitory effect of HCA on the invasion of Matrigel by the cell, indicating that BMP7 is responsible for the anti-migration effect of HCA in HNSCC cells.. HCA treatment led to a remarkable up-regulation of BMP7, which resulted in the attenuation of HNSCC cell invasion.

Topics: Apoptosis; Bone Morphogenetic Protein 7; Carcinoma, Squamous Cell; Cell Movement; Cell Proliferation; Cinnamates; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Neoplasm Invasiveness; Tumor Cells, Cultured

Cinnamaldehyde has been shown to effectively induce apoptosis in a number of human cancer cells. In the present study, cinnamaldehyde derivative-induced apoptosis and its signaling pathways were assessed in p53-wild (SGT) and p53-mutant (YD-10B) human head and neck cancer cells. The cinnamaldehyde derivatives, 2'-hydroxycinnamaldehyde (HCA) and 2'-benzoyloxycinnamaldehyde (BCA), exhibited powerful anti-proliferative effects on SGT and YD-10B cells. The apoptotic effect induced by HCA or BCA was supported by caspase-3, -7, -9 and PARP activation, and confirmed by Annexin V-FITC/PI double staining. HCA induced the expression of p21 in both SGT and YD-10B cells. Furthermore, HCA induced the level of pro-apoptotic Bak1 expression while decreasing the level of anti-apoptotic Bcl-2 in both cell lines, suggesting that HCA induced the cell death pathway in a p53-independent manner. HCA also induced the expression of LC3B in SGT and YD-10B cells. Following pre-incubation with the autophagy inhibitor 3-MA, HCA-induced apoptosis was largely increased in SGT cells, while inhibited in YD-10B cells, suggesting that autophagy may actively contribute to HCA-induced apoptosis. Taken together, these observations suggest that HCA may be an effective therapeutic agent in the treatment of head and neck cancer regardless of p53 status.

Topics: Annexin A5; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cinnamates; Head and Neck Neoplasms; Humans; Reactive Oxygen Species; Signal Transduction