Citral is a New Inducer of Caspase-3 in Tumor Cell Lines

Abstract

Citral, 3,7-dimethyl-2,6-octadien-1-al, a key component of the lemon-scented essential oils extracted from several herbal plants such as lemon grass (Cymbopogon citratus), melissa (Melissa officinalis), verbena (Verbena officinalis) is used as a food additive and as a fragrance in cosmetics. In this study, we investigated the anti-cancer potential of citral and its mode of action. Concentrations of 44.5 muM, comparable to the concentration of citral in a cup of tea prepared from 1 g of lemon grass, induced apoptosis in several hematopoietic cancer cell lines. Apoptosis was accompanied by DNA fragmentation and caspase-3 catalytic activity induction. Citral activity (22.25 microM) was compared to a reference compound like staurosporine (0.7 microM), in respect to DNA fragmentation and caspase-3 enzymatic activity. The apoptotic effect of citral depended on the alpha,beta-unsaturated aldehyde group.

The in vitro study of apoptosis in NB4 cell induced by citral

“…We also detected the activation of caspase-3, which further confirmed results of Wright-Giemsa staining and DNA electrophoresis. Nativ Dudai et al (2005) reported that citral had an anticancer effect on several hematopoietic cell lines, such as U937, HL60, RL12 and BS-24-1, via induction of apoptosis and activation of caspase-3, which agrees with our results.…”

“…It has been demonstrated to be an effective antifungal agent (Mendonca Ade et al 2009;Luo et al 2004). In recent years, it was reported that citral had an antiproliferative effect in certain tumor cell lines and could be a potential anticancer drug (Chaouki et al 2009;Dudai et al 2005). The main goal of the present study was to evaluate the anti-proliferative effect of citral on the NB4 cell line and to understand mechanisms involved in this effect well.…”

“…In recent years, several studies reported that citral was capable of inducing apoptosis in certain tumor cell lines, such as MCF-7, U937 and HL60. (Chaouki et al 2009;Dudai et al 2005). The aim of our study was to investigate the apoptotic effect of citral on the acute promyelocytic leukemia cell line NB4 and the mechanism involved in this effect.…”

Citral and carvone chemotypes from the essential oils of Colombian Lippia alba (Mill.) N.E. Brown: composition, cytotoxicity and antifungal activity

“…Furthermore, 45 µg/mL citral, through caspase 3 activation, induces apoptosis of human (U397, HL60) and mouse (RL-12, BS-24-1) leukaemic cells. In contrast, its derivates, citronellal, citronellol and a product of its metabolism, geraniol, have no effect on the survival of leukaemic cells (Dudai et al 2005), similar to what was observed in this study in HeLa cells.…”

“…According to the National Cancer Institute (USA), the threshold of significance for crude extracts is inhibitory concentration 50 (IC 50 ) < 30 µg/mL (Hennebelle et al 2008) and therefore the citral chemotype was not cytotoxic on Vero non-tumoural cells. Previous studies have shown the cytotoxic activity of citral on tumoural cells (Dudai et al 2005). Citral effectively inhibits the growth of a mouse leukaemia cell line (BS-24-1), with a CC 50 value of 47 µg/mL, but is ineffective on normal spleen cells.…”