Trichostatin A potentiates genistein-induced apoptosis and reverses EMT in HEp2 cells

Abstract

Genistein and trichostatin A (TSA) are two chemotherapeutic compounds with antitumor effects in different types of cancer cell. However, the effects of genistein and TSA on the HEp-2 laryngeal cancer cell line remain to be fully elucidated. In the present study, it was found that genistein and TSA inhibited cell growth and cell migration, and promoted apoptosis in the HEp-2 laryngeal cancer cell line. The HEp-2 cells were treated with genistein, TSA or the two compounds in combination. Cell proliferation and apoptosis were measured using an MTT assay, Annexin V/propidium iodide staining and a TUNEL assay. Cell invasion was determined using a Matrigel-based Transwell assay. Western blotting was used to examine the activation of the Akt pathway and the expression levels of pro-or anti-apoptotic proteins. Treatment with either genistein or TSA alone mildly inhibited cell viability, growth and invasion, and induced the apoptosis of the laryngeal cancer cells, whereas more marked effects were observed in the cells treated with the combination of the two compounds. In addition, genistein reversed endothelial growth factor-induced epithelial-mesenchymal transition (EMT) in the HEp-2 cells, the effect of which were was further increased by joint application with TSA. Treatment of the HEp-2 cells with genistein and TSA led to a significant reduction in the phosphorylation of Akt and activation of its downstream target, and resulted in peroxisome proliferator-activated receptor-γ cleavage, increased expression of B cell lymphoma-2 (Bcl-2)-associated X protein and reduced the expression of Bcl-2. In conclusion, the present study demonstrated that, with the involvement of TSA, genistein exhibited substantial advantages in inhibiting laryngeal carcinoma cell growth, invasion and EMT, and induced apoptosis, compared with genistein treatment alone, which occurred through the regulation of Akt activation and the apoptotic pathway.

Matrine inhibits the invasive and migratory properties of human hepatocellular carcinoma by regulating epithelial‑mesenchymal transition

“…In addition, loss of PTEN function is the most commonly known genetic alteration in the PI3-kinase cascade and is commonly associated with B-Raf proto-oncogene mutations ( 45 ). Furthermore, in line with recent findings, their results revealed that HCC cells with downregulated p-Akt, p27 and pS6 expression exhibited decreased invasion and metastasis ( 46 ). In addition, the induction of EMT by transforming growth factor (TGF)-β is implicated in hepatocarcinogenesis and HCC metastasis.…”

Recent progress on the effects of microRNAs and natural products on tumor epithelial–mesenchymal transition

“…In laryngeal carcinoma HEP-2 cells, genistein showed inhibitory effects on EMT, and significantly reduced cell invasion and migration in vitro. 107 The genistein treatment regimen produced the same findings in ASPC-1 pancreatic cancer cells, and mainly promoted miR-200b expression inhibited by the Notch-1 signaling pathway. 108 Nevertheless, it can downregulate miR-223 expression in GR pancreatic cancer cells and this process can reverse EMT in GR cells, sharing the same effect with miR-223 inhibitor.…”

Phytoestrogens for Cancer Prevention and Treatment

“…This compound can inhibit histone deacetylases in mammalian cells. The combination of TSA with genistein significantly reduces the viability of Hep-2 laryngeal cancer cells [131] and A549 lung cancer cells [132].…”