Tributyrin induces differentiation, growth arrest and apoptosis in androgen-sensitive and androgen-resistant human prostate cancer cell lines

Abstract

Progression to androgen independence remains the main problem that impacts on survival and quality of life in prostate cancer patients. We have investigated the potency of tributyrin, an orally available prodrug of butyrate, to induce growth arrest, differentiation and apoptosis in LNCaP, PC‐3 and TSU‐PR1 human prostate cancer cell lines. Cells were treated with 0.1 to 5 mM tributyrin or sodium butyrate. Growth inhibition, cell cycle arrest and apoptosis induction was assessed using standard methods. Both agents induced a more differentiated, fibroblast‐like phenotype in androgen‐sensitive as well as androgen‐resistant cell lines. Expression of prostate‐specific antigen was increased in LNCaP cells by tributyrin as a indicator of differentiation. The IC50 for sodium butyrate was 2.5 mM in PC‐3 and TSU‐PR1 cells. LNCaP cells exhibited <50% growth inhibition at 5 mM sodium butyrate. However, the IC50 for tributyrin was 0.8 mM in PC‐3 cells, 1.2 mM in TSU‐PR1 cells and 3.1 mM in LNCaP cells. Flow cytometry revealed a strong G1‐arrest after exposure to tributyrin or sodium butyrate. Both agents resulted in a strong increase of apoptosis rates compared with mock‐treated cells. Overall, tributyrin had a 2.5‐ to 3‐fold growth inhibitory and apoptosis‐inducing potency compared with equimolar concentrations of sodium butyrate. Our results demonstrate that tributyrin is more potent than butyrate in regard to cell growth inhibition and apoptosis induction at pharmacologically relevant concentrations. Hence, tributyrin may be a promising candidate for clinical protocols in prostate cancer. Int. J. Cancer 88:245–251, 2000. © 2000 Wiley‐Liss, Inc.

Postbiotics, Metabolic Signaling, and Cancer

“…Tributyrin, a triacylglycerol containing three molecules of butyrate, was tested as a postbiotic agent to avoid the disgusting odor and short half-life of free butyrate. Several in vitro studies on different cancer cell lines showed that tributyrin induces apoptosis at millimolar levels [82][83][84][85][86][87][88]. More importantly, the treatment with tributyrin also induced apoptosis in some in vivo studies.…”

Far-infrared rays control prostate cancer cells in vitro and in vivo

“…For determining cell proliferation, viable cell numbers were counted using the Cell Proliferation Kit II (Roche Diagnostics, Mannheim, Germany) based on the XTT assay 21 .…”

The roles and applications of short-chain fatty acids derived from microbial fermentation of dietary fibers in human cancer

“…Researchers tried to use prodrugs of SCFAs [Trybutirin ( 101 ), phenylbutyrate ( 102 ), and pivaloyloxymethyl butyrate (Pivanex, AN-9) ( 103 , 104 )] and explore their effects on tumors [leukemia ( 102 ), non-small cell lung cancer ( 104 ), and prostate cancer ( 105 )]. These prodrugs had not only similar effects as butyrate in inducing apoptosis ( 101 ) and anti-angiogenesis effects ( 106 ) but also longer half-life and higher stable plasma concentrations ( 107 ). Notably, the doses were still insufficient to exert consistent anti-tumor effects ( 108 ).…”