Anticancer effects of amooranin in human colon carcinoma cell line in vitro and in nude mice xenografts

Abstract

Amooranin (AMR), a natural triterpenoid drug isolated and characterized from Amoora rohituka stem bark, is cytotoxic to SW620 human colon carcinoma cell line with an IC 50 value of 2.9 lg/ml. This novel compound caused depolarization of mitochondrial membrane and decrease of membrane potential, indicating initial signal of apoptosis induction. The percentage of cells with decreased mitochondrial potential ranged from 7.4% at 1 lg/ml to 60.5% at 100 lg/ml AMR. Flow cytometric analysis of apoptosis using Annexin-V-FITC staining showed that the percentage of apoptotic cells ranged from 7.5% at 1 lg/ml to 59.2% at 100 lg/ml AMR. AMR-induced apoptosis was accompanied by redistribution of cytochrome c from mitochondria to cytosol as well as down regulation of Bcl-2 and Bcl-X L proteins in a dose-dependent manner. SW620 human colon carcinoma xenograft mice treated with AMR showed significant reduction in tumor growth rates compared to saline-and doxorubicin-treated groups. The reduction in tumor growth rate was better in xenografts treated with 2 mg/kg AMR than 5 and 10 mg/kg treated mice. The analysis of global gene expression changes induced by AMR in xenograft tumors by microarray hybridization revealed that several genes involved in energy pathways, transport, apoptosis, immune response, nucleic acid metabolism, protein metabolism, cell growth and/or maintenance, signal transduction and cell communication, were affected by this natural cancer drug. These results suggest that the anticancer properties of AMR in SW620 human colon carcinoma cell line are mediated through its effects on functional genomics, targeting the apoptotic process. ' 2006 Wiley-Liss, Inc.

Anti-cancer potential of South Asian plants

“…Organic solvent extracts of A. rohituka bark have been reported to have significant anti-tumor activity against DLA and EAC in mice, and further its selective cytotoxic activity against breast cancer cell line MCF-7 and DLA cells 22,23 . Amooranin, a triterpenic acid extracted from the bark of A. rohituka trees, has significant anti-cancer potential against N-nitrosomethyl ureainduced mammary adenocarcinoma in rats and SW620 human colon carcinoma xenograft in mice 24 . The cytotoxicity of Amooranin against a panel of cancerous cell line including human mammary carcinoma MCF-7, breast carcinoma MDA-468, multi-drug resistant breast carcinoma MCF-7/TH, multidrug-resistant leukemia (CEM/VLB), colon carcinoma (SW620/Ad-300) provides an insight to the possible mode action of A. rohituka.…”

Projection of Exposure and Efficacious Dose Prior to First-in-Human Studies: How Successful Have We Been?

“…Animal disease models are commonly used in many therapeutic areas, as part of target validation, which allows one to study drug behavior in vivo. In oncology, for example, nude mice transplanted with human xenografts are routinely used to assess the in vivo efficacy of anti-tumor agents (12,13). In immunology, rodents with arthritis, induced by agents such as collagen or adjuvant, are also common (14)(15)(16).…”

Determination of Antineoplastic Activity of Rohituka, Aphanamixis Polystachya (Wall) RN Parker in Hela Cells: Correlation with Clonogenicity and DNA Damage

“…The reports regarding the cytotoxic effect of APE in vitro are unavailable. However, triterpenoid amooranin present in Aphanamixis polystachya has been reported to be cytotoxic to HeLa, MCF-7 and SW620 human colon carcinoma cells in vitro [37,38]. The alcoholic extract of the stem bark of Aphanamixis polystachya (AP) showed cytotoxic activity on Ehrlich ascites carcinoma cells in vivo [15].…”

“…The observed antineoplastic action of APE may be due to inhibition of NF-κB, and COX-II. Amooranin has been found to suppress NF-κB, and COX-II activation [38,57]. The suppression of topoisomerase II activity by APE is also not ruled out as it produced micronuclei efficiently.…”