Differentiation of B16-BL6 Melanoma Cells into Microtubule-Associated Protein 2-Positive Cells after Treatment with the Histone Deacetylase Inhibitors Butyrate and Trichostatin A

Abstract

Inhibition of histone deacetylase (HDAC) modulates the expression of many genes and induces cell cycle arrest, apoptosis, and differentiation in several cancer cell lines. Melanoma is a malignant phase of cutaneous melanocytes originally derived from the neural crest and is highly metastatic. A therapeutic agent capable of inducing differentiation of metastatic melanoma cells into a nonmalignant stage would be useful to prevent metastasis. We examined whether HDAC inhibitors can induce differentiation of the murine melanoma cell line B16-BL6 into neural-type cells in vitro. A morphologic change accompanied by extended dendrites was induced in melanoma cells after treatment with the HDAC inhibitors butyrate and trichostatin A (TSA). The altered morphology was similar to that of neural cells. Many of the extended dendrites fused with other dendrites of neighboring cells and had synapse-like knobs on their dendrites. These dendrites showed positive labeling with anti-α/β-tubulin and anti-L1 cell adhesion molecule (L1CAM) antibodies but were seldom stained with phalloidin, suggesting that the neural cell-related proteins were major components of the extended dendrites but that actin stress fibers were not. Furthermore, the mature neuron-specific

Targeted Tumor Therapy Remixed—An Update on the Use of Small-Molecule Drugs in Combination Therapies

“…In addition, decitabine is tested in combination with BRAFi and MEKi to measure the time to progression under this combination (NCT01876641). Similarly, HDACi have been shown to promote MAP2 expression and induce benign neuron-like differentiation in a metastatic melanoma mouse cell line in vitro [ 90 ]. HDAC inhibitors also inhibit the growth of uveal melanoma cells both in vitro and in vivo, and other problem melanoma types (see Section 3.4 ).…”

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

“…There are also evidences that the short-chain fatty acids, including sodium butyrate and valproic acid, could inhibit the proliferation of melanoma cells both in in vitro (e.g., A2058 [ 27 ], B16 cell lines [ 28 ]) and in vivo experiments [ 28 – 29 ] or could abrogate the anticancer drug resistance as they are co-administrated with other chemotherapeutics [ 29 – 30 ]. Nevertheless, there is some controversy about the effects of short-chain fatty acids on the metastatic ability of melanoma cells, since both pro-invasive [ 31 ] and anti-invasive [ 29 , 32 ] activities have been described.…”

Differentiation of Neonatal Human-Induced Pluripotent Stem Cells to Prostate Epithelial Cells: A Model to Study Prostate Cancer Development

“…Additionally, histone deacetylase (HDAC) inhibitors have been shown to activate MAP2 expression and induce benign neuron-like differentiation in a metastatic melanoma mouse cell line [57]. HDAC inhibitors also inhibit the growth of uveal melanoma cells both in vitro and in vivo Figure 1.…”