Gleditsia sinensis fruit extract is a potential chemotherapeutic agent in chronic and acute myelogenous leukemia.
The anti-leukemia activity of the saponin rich Gleditsia sinensis Lam. fruit extract (GSE) was investigated on cancer cell lines and bone marrow cells obtained from consented patients with chronic myelogenous leukemia (CML) and acute myelogenous leukemia (AML) during presentation. The growth inhibitory activity of the extract was determined by [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] (MTS) assay. Colony formation assay was performed to investigate the regeneration potential. Cellular morphology change was studied. Apoptosis was demonstrated by DNA electrophoresis, reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry. The mean concentration to inhibit the cell growth by 50% (MTS50) was 18+/-1.6 micro g/ml for K562 CML cell line and 12+/-1.3 micro g/ml for HL-60 acute promyelocytic leukemia cell line. Patient samples showed a mean MTS50 of 13-28 micro g/ml. Non-malignant hematological disorder bone marrow samples showed a mean MTS50 from 45 to 53 micro g/ml. Loss of regeneration property after treatment with GSE of these two cancer cell lines were confirmed by colony formation assay. GSE was able to induce cell shrinkage in K-562. DNA laddering was observed by incubating the leukemia cells with GSE. RT-PCR demonstrated that the pro-apoptic gene bax was induced while the anti-apoptic gene bcl-2 and cell cycle active gene PCNA were reduced. Flow cytometric analysis showed that the apoptotic effect of GSE on leukemia cell line was time- and dose-dependent. Thus GSE might be potentially used as a chemotherapeutic drug to treat patients with acute and chronic myelogenous leukemia.
Chow
Larry Ming Cheung
LM
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China. bclchow@polyu.edu.hk
Chui
Chung Hin
CH
Tang
Johnny Cheuk On
JC
Teo
Ivy Tuang Ngo
IT
Lau
Fung Yi
FY
Cheng
Gregory Yin Ming
GY
Wong
Raymond Siu Ming
RS
Leung
Thomas Wai Tong
TW
Lai
Ka Bik
KB
Yau
Mabel Yin Chun
MY
Gou
Dean
D
Chan
Albert Sun Chi
AS
D000328:Adult; D001853:Bone Marrow / Q000378:metabolism; D016923:Cell Death; D002455:Cell Division; D003114:Colony-Forming Units Assay; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D016193:G1 Phase; D031501:Gleditsia; D018922:HL-60 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008956:Models, Chemical; D008517:Phytotherapy; D010936:Plant Extracts / Q000378:metabolism*; D028321:Plant Preparations / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D010936:Plant Extracts; D028321:Plant Preparations