A Novel Natural Product, KL-21, Inhibits Proliferation and Induces Apoptosis in Chronic Lymphocytic Leukemia Cells

Abstract

Objective:The aims of this study were to examine the cytotoxic and apoptotic effects of KL-21, a novel plant product (produced by Naturin Natural Products, İzmir, Turkey), on 232B4 chronic lymphocytic leukemia (CLL) cells and to determine the cytotoxic effects on healthy BEAS-2B human bronchial epithelial cells.Materials and Methods:The cytotoxic effect of KL-21 was determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using the caspase-3 colorimetric assay. Changes in mitochondrial membrane potential were determined using the JC-1 dye-based method. Annexin V-FITC/PI double staining was performed to measure the apoptotic cell population. Effects of KL-21 on cell cycle profiles of CLL cells were investigated by flow cytometry.Results:We detected time- and concentration-dependent increases in the cytotoxic effect of KL-21 on 232B4 CLL cells. However, we also showed that, especially at higher concentrations, KL-21 was less cytotoxic towards BEAS-2B healthy cells than towards CLL cells. Annexin-V/PI double staining results showed that the apoptotic cell population increased in 232B4 cells. Increasing concentrations of KL-21 increased caspase-3 enzyme activity and induced loss of mitochondrial membrane potential. KL-21 administration resulted in small increases in the percentage of the cells in the G0/G1 phase while it decreased the S phase cell population up to 1 mg/mL. At the highest concentration, most of the cells accumulated in the G0/G1 phase.Conclusion:KL-21 has a growth-inhibitory effect on 232B4 CLL cells. KL-21 causes apoptosis and cell cycle arrest at G0/G1.

Medicinal Plants from Near East for Cancer Therapy

“…KL-21, a commercial Turkish product contains extracts from Achillea millefolium , Acorus calamus , Cichorium endivia , C. longa , Equisetum arvense , Fumaria officinalis , Juniperus communis , Hypericum perforatum , Lavandula stoechas , Melissa officinalis , N. sativa , Peganum harmala , Rosmarinus officinalis , Silybum marianum , Solidago virgaurea , Taraxacum officinale , Thymus vulgaris , U. dioica , Valeriana officinalis , Viscum album , and Zingiber officinale. KL-21 decreased the viability of 232B4 chronic lymphocytic leukemia cells in a dose- and time-dependent manner, while it did not affect the viability of normal BEAS-2B epithelial cells up to 100 μg/mL ( Gökbulut et al, 2015 ).…”

“…The commercial natural product preparation KL-21 exhibited cytotoxic activity against chronic lymphocytic leukemia cells. The ability of KL-21 to induce apoptosis was correlated with the activation of a mitochondrial/caspase-3-dependent pathway and the inhibition of cell cycle progression through the G0/G1 phase ( Gökbulut et al, 2015 ).…”