A preclinical survey on the efficacy of lactandrate in the treatment of colon carcinoma.

Abstract

PURPOSE:

There has been a recent and dramatic increase in the pace of drug development for colorectal cancer which holds promise to further improve curative therapy. We tested lactandrate, an alkylating ester of D-lactam androsterone, for antineoplastic activity against colon adenocarcinoma in vitro and in vivo.

MATERIALS AND METHODS:

The cytostatic and cytotoxic activity of lactandrate were evaluated in vitro against 9 human colon adenocarcinoma cell lines. The in vitro testing was performed with the sulforhodamine B (SRB) colorimetric assay and the mean concentrations of each drug that generated 50% (GI50) or total (100%) growth inhibition (TGI), as well as the drug concentrations that produced cytotoxicity against 50% of the cultured cells (IC50) were calculated. The in vivo antitumour effect was determined against two rodent colon carcinomas, the Colon 26 and the relatively chemoresistant Colon 38 carcinoma, as well as against the human xenograft CX-1 colon carcinoma.

RESULTS:

Lactandrate displayed a satisfactory activity against the 9 human colon cancer cell lines, inducing significant growth inhibition and cytotoxicity. Lactandrate induced antiproliferative activity against colon cancer cell lines linearly correlated with the carcinoembryonic antigen (CEA) production. There was a non-linear polynomial correlation between CEA production and the cytotoxic effect of lactandrate. The more differentiated cell lines DLD-1 and HCC2998 appeared more resistant to the cytostatic effect of lactandrate. In vivo, the compound produced a significant antitumour activity against Colon 26 and Colon 38, as well as a moderate antitumour effect against CX-1 colon carcinoma.

CONCLUSION:

Preclinical research supports the high in vitro and in vivo antitumour potential of lactandrate against colon carcinoma. Therefore, lactandrate represents an important candidate drug for further clinical development.

• Authors: D T P Trafalis, G D Geromichalos, N Bountouroglou, D Koumbi, M Kontos, D Sougias, P Dalezis, P Karamanakos, A Papageorgiou, C Camoutsis, A E Athanassiou
• Journal: Journal of B.U.ON. : official journal of the Balkan Union of Oncology (J BUON) 2005 Apr-Jun Vol. 10 Issue 2 Pg. 227-34 ISSN: 1107-0625 [Print] Cyprus
• PMID: 17343334 (Publication Type: Journal Article)