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

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.

Targeting AMPK signaling in combating ovarian cancers: opportunities and challenges

“…Triterpenoids from a wide range of botanicals have already been confirmed to possess antiproliferative [174][175][176] and anti-invasive [177,178] features. More than 50 triterpenoids have been extracted from bitter melon; however, their biological functions have yet to be investigated in detail.…”

Simaroubaceae family: botany, chemical composition and biological activities

“…AECHL-1, a quassinoid isolated from Ailanthus excelsa, inhibited the growth of melanoma, prostate cancer, carcinoma and mammary adenocarcinoma cell lines. This last molecule has been proved to be more potent than paclitaxel and cisplatine, drugs commonly used in therapeutic (Lavhale et al, 2009). Quassimarin, isolated from Quassia amara, showed activity against lymphocytic leukemia in rats, and carcinoma nasopharynx cells in human (Kupchan and Streelman, 1976).…”

Kuguacin J, a Triterpenoid from Momordica charantia Linn: A Comprehensive Review of Anticarcinogenic Properties

“…Recently, several triterpenoids from various plants have been reported to feature antiproliferative [51][52][53] and anti-invasive [54,55] bioactive components. More than 50 triterpenoids have been isolated from bitter melon, but their biological activities have yet to be explored in detail.…”