RETRACTED: A Novel Triterpenoid Isolated from the Root Bark of Ailanthus excelsa Roxb (Tree of Heaven), AECHL-1 as a Potential Anti-Cancer Agent (Retracted Article)

被引:35
作者
Lavhale, Manish S.
Kumar, Santosh
Mishra, Shri Hari
Sitasawad, Sandhya L.
机构
[1] Pharmacy Department, Faculty of Technology and Engineering, The M. S. University of Baroda, Vadodara, Gujarat
[2] National Centre for Cell Science, NCCS Complex, University of Pune Campus, Ganeshkhind, Pune, Maharashtra
关键词
NECROSIS-FACTOR-ALPHA; INHIBITOR; CANCER; PHOSPHORYLATION; DERIVATIVES; DESIGN;
D O I
10.1371/journal.pone.0005365
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: We report here the isolation and characterization of a new compound Ailanthus excelsa chloroform extract-1 (AECHL-1) (C29H36O10; molecular weight 543.8) from the root bark of Ailanthus excelsa Roxb. The compound possesses anticancer activity against a variety of cancer cell lines of different origin. Principal Findings: AECHL-1 treatment for 12 to 48 hr inhibited cell proliferation and induced death in B16F10, MDA-MB-231, MCF-7, and PC3 cells with minimum growth inhibition in normal HEK 293. The antitumor effect of AECHL-1 was comparable with that of the conventional antitumor drugs paclitaxel and cisplatin. AECHL-1-induced growth inhibition was associated with S/G(2)-M arrests in MDA-MB-231, MCF-7, and PC3 cells and a G(1) arrest in B16F10 cells. We observed microtubule disruption in MCF-7 cells treated with AECHL-1 in vitro. Compared with control, subcutaneous injection of AECHL-1 to the sites of tumor of mouse melanoma B16F10 implanted in C57BL/6 mice and human breast cancer MCF-7 cells in athymic nude mice resulted in significant decrease in tumor volume. In B16F10 tumors, AECHL-1 at 50 mu g/mouse/day dose for 15 days resulted in increased expression of tumor suppressor proteins P53/p21, reduction in the expression of the oncogene c-Myc, and downregulation of cyclin D1 and cdk4. Additionally, AECHL-1 treatment resulted in the phosphorylation of p53 at serine 15 in B16F10 tumors, which seems to exhibit p53-dependent growth inhibitory responses. Conclusions: The present data demonstrate the activity of a triterpenoid AECHL-1 which possess a broad spectrum of activity against cancer cells. We propose here that AECHL-1 is a futuristic anti-cancer drug whose therapeutic potential needs to be widely explored for chemotherapy against cancer.
引用
收藏
页数:11
相关论文
共 32 条
[1]   The discovery and development of cisplatin [J].
Alderden, RA ;
Hall, MD ;
Hambley, TW .
JOURNAL OF CHEMICAL EDUCATION, 2006, 83 (05) :728-734
[2]  
[Anonymous], CANC FACTS FIG
[3]   Platinum-intercalator conjugates: From DNA-targeted cisplatin derivatives to adenine binding complexes as potential modulators of gene regulation [J].
Baruah, H ;
Barry, CG ;
Bierbach, U .
CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2004, 4 (15) :1537-1549
[4]   CELLULAR ONCOGENES AND RETROVIRUSES [J].
BISHOP, JM .
ANNUAL REVIEW OF BIOCHEMISTRY, 1983, 52 :301-354
[5]  
Brady H, 2002, CANCER RES, V62, P1439
[6]   Tannins and human health: A review [J].
Chung, KT ;
Wong, TY ;
Wei, CI ;
Huang, YW ;
Lin, Y .
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION, 1998, 38 (06) :421-464
[7]  
CORDELL GA, 1978, LLOYDIA, V41, P166
[8]  
CRAGG GM, 2004, ENCY LIFE SUPPORT SY
[9]   Pharmacological activities of natural triterpenoids and their therapeutic implications [J].
Dzubak, Petr ;
Hajduch, Marian ;
Vydra, David ;
Hustova, Alica ;
Kvasnica, Miroslav ;
Biedermann, David ;
Markova, Lenka ;
Urban, Milan ;
Sarek, Jan .
NATURAL PRODUCT REPORTS, 2006, 23 (03) :394-411
[10]  
Ferlay J., 2001, GLOBOCAN 2000 CANC I