Olean-12-Eno[2,3-c] [1,2,5]Oxadiazol-28-Oic Acid (OEOA) Induces G1 Cell Cycle Arrest and Differentiation in Human Leukemia Cell Lines

Abstract

Oleanolic acid (3β-hydroxy-olea-12-en-28-oic acid) is a natural pentacyclic triterpenoic acid found in many fruits, herbs and medicinal plants. In the past decade, increasing evidence has suggested that oleanolic acid exhibits inhibitory activities against different types of cancer including skin cancer and colon cancer, but not leukemia. We report here that a derivative of oleanolic acid, olean-12-eno[2,3-c] [1], [2], [5]oxadiazol-28-oic acid (designated OEOA) effectively blocks the proliferation of human leukemia cells. OEOA significantly reduces cell proliferation without inducing cell death in three types of leukemia cell lines, including K562, HEL and Jurket. Moreover, exposure of K562 cells to OEOA results in G1 cell cycle arrest, with a concomitant induction of cyclin-dependent kinase inhibitor p27 and downregulation of cyclins and Cdks that are essential for cell cycle progression. Interestingly, OEOA also enhances erythroid differentiation in K562 cells through suppressing the expression of Bcr-Abl and phosphorylation of Erk1/2. These findings identify a novel chemical entity for further development as therapeutics against leukemia.

Oleanolic acid derivative SZC014 inhibit cell proliferation and induce apoptosis of human breast cancer cells in a ROS-dependent way

“…OA and its derivatives have been shown to exhibit an inhibitory effect on tumor growth in vivo and induce apoptosis in human breast cancer cells [21,22]. The present study demonstrated that SZC014, a novel derivative of OA with improved stability and water solubility, effectively inhibited breast cancer cells growth and enhanced apoptosis induction dose-dependently, as compared with OA.…”

LukS-PV, a component of Panton-Valentine leukocidin, exerts potent activity against acute myeloid leukemia in vitro and in vivo

“…Investigators have continued to search for and develop drugs that are more selective for effective treatment of leukemia (Döhner et al, 2010;Dores et al, 2012). Among these strategies, apoptosis and differentiation-based targeted therapies have become a research hotspot Gao et al, 2012;Ng et al, 2013;Zhang et al, 2012).…”

Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: Preclinical and clinical evidence

“…Olean-12-Eno[2,3-c] [1,2,5] oxadiazol-28-oic acid (OEOA), synthetic derivative of OA, induced G 1 cell cycle arrest as well as differentiation in human leukemia cell lines, K562, HEL and JURKAT [62]. Three new active oleanolic vinyl bornates inhibited the growth of leukemia cells (Jurkat and K562) and Burkitt’s lymphoma cells (Jijoye) without concomitant inhibition of non-tumoral human fibroblasts [63].…”