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.
Highlights
Leukemia is a malignant disease which broadly covers a number of cancers of the blood, bone marrow, and lymphoid systems
Based on how the disease develops and the blood cells affected, they are categorized into four main types, i.e. acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelocytic leukemia (AML), and chronic myelocytic leukemia (CML) [1,2,3,4]
A slight inhibition on the cell growth of a human hepatocellular liver carcinoma, HepG2, was observed at 10 mM (Fig. 2E). These results suggest the selectivity of OEOA to leukemia cells
Summary
Leukemia is a malignant disease which broadly covers a number of cancers of the blood, bone marrow, and lymphoid systems. Based on how the disease develops (acute or chronic) and the blood cells affected (lymphocytes or myelocytes), they are categorized into four main types, i.e. acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelocytic leukemia (AML), and chronic myelocytic leukemia (CML) [1,2,3,4]. While leukemia affects both adults and children of both genders with most cases (.90%) diagnosed in adults, leukemia is the most common form of cancer in children and adolescents, accounting for about one third of cancers in individuals aged under 20. We report the characterization of an OA derivative, olean-12-eno[2,3-c] [1,2,5]oxadiazol-28oic acid (OEOA), which displays anti-leukemia properties
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