p-hydroxycinnamaldehyde and Carcinoma--Squamous-Cell

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

p-Hydroxylcinnamaldehyde (CMSP) has been identified as an inhibitor of the growth of various cancer cells. However, its function in oesophageal squamous cell carcinoma (ESCC) and the underlying mechanism remain unclear. The aim of the present study was to characterize the differentiation effects of CMSP, as well as its mechanism in the differentiation of ESCC Kyse30 and TE-13 cells. The function of CMSP in the viability, colony formation, migration and invasion of Kyse30 and TE-13 cells was determined by MTS, colony-formation, wound healing and transwell assays. Western blotting and pull-down assays were used to investigate the effect of CMSP on the expression level of malignant markers of ESCC, as well as the activity of MAPKs, RhoA and GTP-RhoA in Kyse30 and TE-13 cells. We found that CMSP could inhibit proliferation and migration and induce Kyse30 and TE-13 cell differentiation, characterized by dendrite-like outgrowth, decreased expression of tumour-associated antigens, as well as the decreased expression of malignant markers. Furthermore, increased cAMP, p-P38 and decreased activities of ERK, JNK and GTP-RhoA, were detected after treatment with CMSP. These results indicated that CMSP induced the differentiation of Kyse30 and TE-13 cells through mediating the cAMP-RhoA-MAPK axis, which might provide new potential strategies for ESCC treatment.

Topics: Acrolein; Animals; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Cinnamates; Cyclic AMP; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagus; Humans; MAP Kinase Signaling System; Medicine, Chinese Traditional; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; rhoA GTP-Binding Protein

The Pim-1 kinase regulates cell survival, proliferation, and differentiation and is overexpressed frequently in many malignancies, including leukemia and skin cancer. In this study, we used kinase profiling analysis to demonstrate that 2'-hydroxycinnamicaldehyde (2'-HCA), a compound found in cinnamon, specifically inhibits Pim-1 activity. Cocrystallography studies determined the hydrogen bonding pattern between 2'-HCA and Pim-1. Notably, 2'-HCA binding altered the apo kinase structure in a manner that shielded the ligand from solvent, thereby acting as a gatekeeper loop. Biologically, 2'-HCA inhibited the growth of human erythroleukemia or squamous epidermoid carcinoma cells by inducing apoptosis. The compound was also effective as a chemopreventive agent against EGF-mediated neoplastic transformation. Finally, 2'-HCA potently suppressed the growth of mouse xenografts representing human leukemia or skin cancer. Overall, our results offered preclinical proof of concept for 2'-HCA as a potent anticancer principle arising from direct targeting of the Pim-1 kinase.

Topics: Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Cinnamates; Female; Humans; Keratinocytes; Leukemia, Erythroblastic, Acute; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Models, Molecular; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-pim-1; Random Allocation; Skin Neoplasms; Xenograft Model Antitumor Assays

2'-Hydroxycinnamaldehyde (HCA) exerts antitumor activity against several human cancer cell lines. However, its antitumor activity in oral cancer has not been demonstrated.. The antitumor activity of HCA was assessed in oral cancer cell lines and in a rat oral tumor model.. Cell cycle analysis confirmed that HCA showed anti-proliferative activity via cell cycle arrest at the G(2)/M-phase and increased the number of cells in the sub-G(1) (apoptotic cells) phase in SCC-15 and HEp-2 oral cancer cells. Additionally, direct injection of HCA into an RK3E-ras-Fluc-induced tumor significantly inhibited growth of the tumor mass. Histological analysis showed that HCA decreased tumor cell proliferation and induced apoptosis in a rat tumor model.. Taken together, these observations suggest the potential value of HCA as a candidate for the treatment of oral cancer.

Topics: Animals; Antineoplastic Agents; Apoptosis; Blotting, Western; Carcinoma, Squamous Cell; Cell Cycle; Cell Proliferation; Cinnamates; Humans; Immunoenzyme Techniques; In Vitro Techniques; Male; Mouth Neoplasms; Rats; Rats, Sprague-Dawley; Xenograft Model Antitumor Assays