Treatment of Hematological Malignancies with Glycyrrhizic Acid.
The current study examined the effectiveness of glycyrrhizic acid (GA) in reducing cell viability and inducing apoptosis in human chronic myeloid leukemia (CML) in vitro and a mouse lymphoma in vivo. Additionally, we assessed GA as a candidate for combinational therapy in CML along with the current frontline treatment, imatinib (IM). Treatment of K562 CML cells with GA alone resulted in significant induction of apoptosis and loss of cell viability. GA was well tolerated by peripheral blood mononuclear cells (PBMCs) up to 2 mM doses which were subsequently used in combination with IM. Co-treatment of CML with GA and IM greatly enhanced the levels of apoptosis in human CML. The effectiveness of GA was not limited to in vitro studies as treatment of EL-4 lymphoma-bearing mice with GA (50 or 500 mg/kg/day) led to significant dose-related decrease in tumor burden that correlated with a significant increase in the level of apoptotic tumors in vivo. The broad activity of GA against different tumor cell types, its tolerance by PBMCs and synergistic effects when combined with IM suggests that GA may be a viable candidate for combinational treatment strategies in CML and other hematological malignancies.
Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA, U.S.A.
Bryan J
BJ
Hostetler
Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA, U.S.A.
Olga N
ON
Uchakina
Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA, U.S.A.
Hao
H
Ban
Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA, U.S.A. mckallip_r@mercer.edu.
Robert J
RJ
McKallip
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D019695:Glycyrrhizic Acid / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008223:Lymphoma / Q000188:drug therapy*; D051379:Mice; D009368:Neoplasm Transplantation; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D019695:Glycyrrhizic Acid; D000068877:Imatinib Mesylate
Glycyrrhizic acid; apoptosis; chronic myelogenous leukemia; hyaluronic acid