Antiproliferative Effect of Phenylbutyrate in AsPC-1 Pancreatic Cancer Cell Line

ABSTRACT

PURPOSE: Phenylbutyrate is an effective redifferentiating agent in several human cancers. Recently phenylbutyrate has been reported to inhibit histone deacetylase activity. We investigated the effects of sodium 4-henylbutyrate (Na-4-PB) on cell proliferation in a human pancreatic cancer cell line. METHODS: A human pancreatic cancer cell line, Aspc-1 was purchased from Korean Cell Line Bank. Antiproliferative effects of sodium 4-phenylbutyrate were measured by MTT assay and their mechanisms were evaluated by apoptosis assay and cell cycle analysis. RESULTS: After 3 days of treatment with Na-4-PB at the concentration of 2.5, 5, 7.5, and 10 mM, relative growth inhibition compared to control was 21.3+/-8.3% (mean+/-SD), 37.8+/-2.3%, 46.7+/-0.5%, and 56.7+/-1.7% respectively (p < 0.05). Antiproliferative effect of Na-4-PB was also time-dependent. Combination treatment with Na-4-PB and troglitazone, a PPARg agonist, increased antiproliferative effects but was not synergistic. After 48 hour treatment with Na-4-PB, early apoptotic cell population in control, 2.5, and 5 mM of Na-4-PB was 29.6%, 44.2%, and 65.9%, respectively. After 24 hour treatment with Na-4- PB, G0/G1 phase population in control, 2.5, and 5 mM of Na-4-PB was 55.0%, 67.4%, and 65.8%, respectively. CONCLUSION: Na-4-PB inhibited pancreatic cancer cell proliferation by inducing apoptosis and cell cycle arrest at G0/G1 phase in time- and dose-dependent manner. Combination treatment with Na-4-PB and other chemotherapeutic agents such as troglitazone, a PPARg agonist, can enhance antiproliferative effects. Na-4-PB might be a promising potential therapeutic agent for patients with pancreatic cancer.