The Novel Synthetic Triterpene Methyl 3β-<i>O</i>-[4-(2-Aminoethylamino)-4-oxo-butyryl]olean-12-ene-28-oate Inhibits Breast Tumor Cell Growth <i>in</i> <i>Vitro</i> and <i>in</i> <i>Vivo</i>

• DOI: 10.1248/cpb.c20-00353
• Publication Date: 2020-09-30T22:18:37Z
• Authors: Bin Feng; Chunhui Zhao; Jiaqi Li; Jiawen Yu; Yang Zhang; Xiyue Zhang; Tian Tian; Longxuan Zhao
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Caspase 3; Cytochromes c; Mice, Nude; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Triterpenes; 3. Good health; 03 medical and health sciences; Proto-Oncogene Proteins c-bcl-2; A549 Cells; MCF-7 Cells; Ursolic Acid; Animals; Humans; Female; Drug Screening Assays, Antitumor; Oleanolic Acid; Cell Proliferation; HeLa Cells; bcl-2-Associated X Protein

Oleanolic and ursolic acids were used as lead compounds to synthesize a series of pentacyclic triterpenoid derivatives bearing ethylenediamine, butanediamine, or hexanediamine groups at the C-3 position. The potential antiproliferative activity of these compounds was examined in A549 (human non-small cell lung cancer cells), MCF-7 (human breast cancer cells), and HeLa (human cervical carcinoma cells) cells. Methyl 3β-O-[4-(2-aminoethylamino)-4-oxo-butyryl]olean-12-ene-28-oate (DABO-Me) was identified as a promising antiproliferative agent in vitro and in vivo. DABO-Me strongly suppressed the proliferation of A549, MCF-7, and HeLa cells (IC50 = 4-7 µM). In MCF-7 cells, DABO-Me upregulated the pro-apoptotic protein Bax, downregulated the anti-apoptotic protein Bcl-2, promoted the release of cytochrome c, and activated caspase-3/9. Transwell and flow cytometry assays showed that DABO-Me inhibited MCF-7 cell proliferation, migration, and invasion, and induced apoptosis and S phase arrest. In vitro and in vivo experiments indicated that DABO-Me inhibited MCF-7 cell proliferation and suppressed tumor growth. Taken together, these results indicate that DABO-Me could be developed as an effective antitumor drug.