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

Joseph Alan Bauer,Manish S. Lavhale,Shri Hari Mishra,Sandhya L. Sitasawad,Santosh Kumar

doi:10.1371/journal.pone.0005365

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.

Highlights

According to the World Health Organization based on morbidity, mortality, economic burden, and emotional hardship, cancer may be considered the most onerous health problem afflicting people worldwide [1]
The present data demonstrate the activity of a triterpenoid Ailanthus excelsa chloroform extract-1 (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

Summary

Introduction

According to the World Health Organization based on morbidity, mortality, economic burden, and emotional hardship, cancer may be considered the most onerous health problem afflicting people worldwide [1]. Most of these compounds exhibit cell toxicity and can induce genotoxic, carcinogenic and teratogenic effects in nontumor cells, and some of them failed in earlier clinical studies [4,5] Another most widely used metal-based drug at present against selected types of cancers is cisplatin [6], but use of cisplatin in curative therapy was associated with some serious clinical problems, such as severe normal tissue toxicity and resistance to the treatment [7]. These side effects limit their use as chemotherapeutic agents despite their high efficacy in treating target malignant cells. The compound possesses anticancer activity against a variety of cancer cell lines of different origin

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