Anti-tumor Efficacy and Safety of Zeylenone on Acute T Lymphoblastic Leukemia
10.13422/j.cnki.syfjx.20201129
- VernacularTitle:山椒子烯酮对急性T淋巴细胞白血病的抗肿瘤药效及安全性评价
- Author:
Fei-fei WANG
1
;
Shu-xian YANG
2
;
Li-wu HUANG
3
;
Min PANG
2
;
Yu SHAN
2
;
Xiao-qin HU
1
;
Li-yong LI
2
;
Li CAO
2
Author Information
1. College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530001, China
2. Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences ＆ Peking Union Medical College, Beijing 100193, China
3. The Renmin University Hospital, Beijing 100872, China
- Publication Type:Research Article
- Keywords:
acute T lymphocytic leukemia;
zeylenone;
cell apoptosis;
anti-tumor;
Molt-4 cell
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2020;26(11):100-106
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the anti-tumor efficacy, mechanism and safety of zeylenone on acute T lymphocytic leukemia. Method:In vitro, Molt-4 cells were treated with various concentrations of zeylenone (0.2, 0.4, 0.8, 1.6, 3.2 μmol·L-1) for 48 h, and the cell viability was measured with cell counting kit-8 (CCK-8) assay. nonobese diabetic-severce combined immunodeficient mice（NOD/SCID） mice were randomly divided into six groups: normal group, model group, vincristine group (1 mg·kg-1), low-dose zeylenone group (12.5 mg·kg-1), medium-dose zeylenone group (25 mg·kg-1), high-dose zeylenone group (50 mg·kg-1). With the exception of normal group, mice were pre-irradiated with 60Co and inoculated subcutaneously with Molt-4 cells to establish the Molt-4 xenograft model. Then NOD/SCID mice were sacrificed after 13 days of administration. The tumor inhibition rates, relative tumor growth rates and organ indexes were calculated. Hematoxylin and eosin (HE) staining was used to observe the pathological changes of liver and spleen tissues in mice. The expressions of phosphorylation signal transducer and activator of transcription (p-STAT3), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and cysteine aspartate-specific protease-3 (Caspase-3) were detected in tumor tissues by Western blot. Result:In vitro, zeylenone had an obvious inhibitory effect on Molt-4 cells. IC50 values of zeylenone was 1.49 μmol·L-1. In vivo, compared with the model group, medium and high-dose zeylenone groups had significant tumor inhibition effects, with the inhibition rates of 50.24% and 60.75%, respectively (P<0.01). Additionally, liver and spleen injuries were slight in the above mentioned two groups compared with the vincristine group, indicating that zeylenone was safe. Western blot analysis showed that medium and high-dose zeylenone groups showed significant declines in proteins p-STAT3, Caspase-3 and Bcl-2, and marked increases in pro-apoptotic protein Bax compared with the model group (P<0.05, P<0.01). Conclusion:zeylenone could obviously inhibit the proliferation and induce the apoptosis of Molt-4 cells; and its mechanism may be related to the down-regulation of p-STAT3, Caspase-3, Bcl-2 and the up-regulation of Bax expressions. In addition, zeylenone had less damage to liver and spleen, and was safer than vincristine.
