Investigational New Drugs 18: 221–230, 2000. © 2000 Kluwer Academic Publishers. Printed in the Netherlands. 221 Studies on the cytotoxic, biochemical and anti-carcinogenic potentials of ninhydrin on Ehrlich ascites carcinoma cell-bearing Swiss albino mice S. Qureshi, O.A. Al-Shabanah, A.M. Al-Bekairi, M.M. Al-Harbi, N.M. Al-Gharably & M. Raza Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia Key words: Ehrlich ascites, ninhydrin, cytotoxicity, biochemical changes, anticarcinogenicity Summary Ninhydrin (2,2-dihydroxy-1, 3-indane dione) was evaluated for its antitumor and cytotoxic properties in Ehrlich as- cites carcinoma cell (EAC Cell)-bearing mice. The rationale behind this study has been mainly the literature reports of its characteristic interference with DNA synthesis and calcium homeostasis. Antitumor activity was evaluated from the total count and viability of EAC cells in addition to their nucleic acid, protein, non-protein sulfhydryls (NP-SH) and malondialdehyde (MDA) contents. The EAC cell-bearing animals were also observed for the effect on their survival and body weight variations. In addition, the tumors grown at the site of injection were evaluated for histopathological changes. Ninhydrin treatments (5, 10 and 20 mg/kg/day) abate the increase in body weight and advanced the duration of survival in EAC cell-bearing mice. The results on histopathological investigations show retardation in tumor growth, decreased frequency of mitotic figures and hair follicles and an increased necrosis in the tumor by ninhydrin treatment. Our results on cytotoxicity, which demonstrated compression in the number of EAC cells and their viability substantiate these data. The results of biochemical studies on EAC cells exhibit a reduction in the levels of DNA, RNA, proteins and NP-SH with a subsequent increase in the concentrations of MDA after ninhydrin treatment. Inhibition in tumor growth was dose dependently significant with the same dose regimen. The observed cytotoxic and antitumor activity of ninhydrin was comparable to cyclophosphamide. The possible mode of action of ninhydrin-induced cytotoxic and antitumor activity appear to be due to its interference with mitochondrial function resulting in inhibition of DNA synthesis, an effect that is being investigated further. Figure 1. Introduction Ninhydrin (2,2-dihydroxy-1, 3-indane dione; CAS No. 485-47-2) is an important laboratory reagent, widely used to unmask the free amino acids, carboxyl groups in peptides and in the detection of some ba- sic drugs or their metabolites by certain specialized procedures. Chemical structure of ninhydrin (Figure 1) shows it to be a carbonyl compound with reactive keto groups responsible for hydrogen accepting property [1]. On the other hand because of its potential to generate hydroxyl radicals, ninhydrin has been described as an oxidant. Most of the free radical producing com- pounds are well known for their carcinogenic, cyto- toxic and/or anti-cancer properties [2,3,4]. However, despite the oxidant nature of ninhydrin, there is a paucity of literature on its carcinogenic and cyto- toxic potentials. In an earlier study [5] ninhydrin has been reported as a strong promoter of stage I skin tumor-induced by 7,12-dimethyl benz-anthracene that declined to function as a stage II or complete tumor promoter. Furthermore, it was not found to alter the activity of ornithine decarboxylase. Reports in liter- ature reveal that ninhydrin inhibit citric acid cycle