BPB Reports

Paper Details

BPB Reports
Vol. 3 No. 2 p.56-59 2020
Report
(–)-Isostemonamine Can Enhance the Anti-Proliferative Activity of Trichostatin A Against Human Breast Cancer MDA-MB-231 Cells
  • Shuso Takeda (Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU))
Masayo Hirao-Suzuki 1) , Shuso Takeda 1) , Takayuki Iwata 2) , Satoshi Fujita 2) , Taishi Tomiyama 2) , Masufumi Takiguchi 1) , Akihisa Toda 3) , Mitsuru Shindo 2)
1) Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU) , 2) Institute for Materials Chemistry and Engineering, Kyushu University , 3) Department of Hygienic Chemistry, Daiichi University of Pharmacy
Received: January 06, 2020;   Accepted: February 13, 2020;   Released: March 12, 2020
Keywords: (–)-isostemonamine, trichostatin A, MDA-MB-231 cells, Stemona alkaloid
Abstracts

Recent findings established (–)-isostemonamine as an anti-proliferator for estrogen receptor α-negative human breast cancer cells, MDA-MB-231, known to grow/divide at an aggressive rate. However, ST-4, a thioamide derivative of (–)-isostemonamine, is believed to not affect the viability of these cells. Epigenetic changes, such as DNA methylation and histone modification, are involved in the progression of many cancers, including breast cancer. In the present study, we investigated whether ST-4 and its related compounds (ST-3 and ST-5) can potentiate the anti-proliferative activity of the established epigenetic modifiers, 5-aza-2’-deoxycytidine (5-aza-dC; a DNA methyltransferase 1 inhibitor), trichostatin A (TSA; a class I/II histone deacetylase inhibitor), and etoposide (a DNA topoisomerase IIα inhibitor). Data obtained from this study demonstrate that, among the studied compounds, ST-4 displays the strongest enhancement of the anti-proliferative activity of TSA, against MDA-MB-231 cells (IC20 of TSA = 14 ± 3.4 nM versus that of TSA/ST-4 combination = 7.8 ± 1.1 nM). However, this effect was not observed at higher concentrations of above 25 nM of TSA, at which the IC50 values of TSA with or without ST-4 were not significantly different (30 ± 4.4 nM versus 28 ± 1.4 nM, respectively). Results from the study suggest that combining ST-4 with established anti-cancer agents could potentiate the latter’s anti-proliferative activity, thereby potentially minimizing the concentration of these agents needed for optimal clinical efficacy and safety.