A Novel Triterpenoid Isolated from the Root Bark of Ailanthus
excelsa Roxb (Tree of Heaven), AECHL-1 as a Potential Anti-Cancer
Agent |
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Authors: | Manish S Lavhale Santosh Kumar Shri Hari Mishra Sandhya L Sitasawad |
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Institution: | 1. Pharmacy Department, Faculty of Technology and Engineering, The M. S.
University of Baroda, Vadodara, Gujarat, India.; 2. National Centre for Cell Science, NCCS Complex, University of Pune
Campus, Ganeshkhind, Pune, Maharashtra, India.;Cleveland Clinic, United States of America |
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Abstract: | BackgroundWe 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 anti-cancer activity against a variety of cancer cell lines of
different origin.Principal FindingsAECHL-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/G2-M
arrests in MDA-MB-231, MCF-7, and PC3 cells and a G1 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
µg/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.ConclusionsThe 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. |
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