Cancer has become a major public health problem worldwide and the number of deaths due to this disease is increasing almost exponentially. In the constant search for new treatments, natural products of plant origin have provided a variety of new compounds to be explored as antitumor agents. Tabernaemontana catharinensis is a medicinal plant that produces alkaloids with expressive antitumor activity, such as heyneanine, coronaridine and voacangine. The aim of present study was firstly to screen the cytotoxic activity of the indole alkaloids heyneanine, coronaridine and voacangine against HeLa (human cervix tumor), 3T3 (normal mouse embryo fibroblasts), Hep-2 (human laryngeal epithelial carcinoma) and B-16 (murine skin) cell lines by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide); and secondly to analyze the apoptotic activity, cell membrane damage and genotoxicity of the compound that showed the best cytotoxic activity against the tumor cell lines tested. Coronaridine was the one that exhibited greater cytotoxic activity in the laryngeal carcinoma cell line Hep-2 (IC50 = 54.47 µg/mL) than the other alkaloids tested (voacangine IC50 = 159.33 µg/mL, and heyneanine IC50 = 689.45 µg/mL). Coronaridine induced apoptosis in cell lines 3T3 and Hep-2, even at high concentrations. The evaluation of genotoxicity by comet assay showed further that coronaridine caused minimal DNA damage in the Hep-2 tumor cell line, and the LDH test showed that it did not affect the plasma membrane. These results suggest that further investigation of coronaridine as an antitumor agent has merit.

The brown seaweed Fucus vesiculosus (Fucales, Fucaceae) was screened for its protective activity using doxorubicin-induced DNA damage in human lymphocytes. In this study, we assessed the genotoxic and antigenotoxic potential of three different concentrations (0.25, 0.5 and 1.0 mg mL-1) of F. vesiculosus aqueous extract using the chromosome aberration and Comet assays. Treatment of human lymphocyte cultures with 0.25, 0.5 and 1.0 mg mL-1 F. vesiculosus aqueous extract had no effect on the chromosome aberration frequency or on the extent of DNA damage detected by the Comet assay. The antigenotoxic effects of the extract were tested in human lymphocyte cultures treated with 15 µg mL-1 of doxorubicin, either alone or combined with the different concentrations of the extract, which was added to the cultures before, simultaneously with or after the doxorubicin. Only when lymphocytes were pre-treated with extract there was a reduction in doxorubicin-induced chromosome aberrations and DNA damage as detected by the Comet assay. These results demonstrate that F. vesiculosus aqueous extract is not genotoxic in cultured human lymphocytes and indicate that when added to lymphocyte cultures before doxorubicin it has antigenotoxic activity against doxorubicin-induced DNA damage.

The effects of H2O2, Fe2+ and Fe3+ on curcumin-induced clastogenicity were evaluated in CHO cells. Curcumin combined with H2O2 did not increase the chromosomal aberrations more than expected based on a simple additive effect. In contrast, the combination of curcumin-Fe significantly decreased the total number of chromosomal aberrations and the number of abnormal metaphases. The clastogenicity of curcumin may be related to its pro-oxidant properties and its ability to generate free radicals.

The base analogue 2-chlorodeoxyadenosine (2-CdA) used for therapy in chronic resistant and advanced lymphoproliferative disorders, is cytotoxic for both dividing and non-dividing lymphocytes. The present work evaluated the clastogenic potential of this drug in vitro in human lymphocytes in culture and in vivo in BALB/c mice bone marrow cells. In human lymphocytes, the clastogenic effect of 2-CdA was studied in G1, S and G2 phases of the cell cycle, using three different concentrations (10, 20 and 40 mug/mL). The endpoints analyzed included mitotic index (MI), proliferation index (PI), sister chromatid exchange (SCE), and chromosomal aberration (CA). Statistical analysis by a variance (ANOVA) test showed a significant increase (p < 0.05) in CA frequencies for cells treated during the S phase, but the MI did not vary. The concentrations tested did not produce a significant increase in the mean frequency of SCEs, nor did they change the cell PI in the G1 and S phases. The concentrations in vivo tested were 0.25, 0.375 and 0.5 mg/kg body weight. In this assay, alterations in CA frequencies and MI were not observed at the dose levels tested. Therefore, the results indicate a clastogenic effect of 2-CdA in human lymphocyte cultures.

Existe considerável interesse na identificação de componentes da dieta que têm a capacidade de proteger contra as aberrações cromossômicas induzidas pelos agentes antitumorais. Os ácidos graxos e seus constituintes são capazes de atuar como seqüestradores de radicais livres. Na presente investigação, as células da medula óssea dos animais tratados simultaneamente com o óleo de oliva (10 ml/kg de peso corporal) e doxorubicina (DXR; 90 mg/kg de peso corporal) apresentaram uma significativa redução no total de aberrações cromossômicas e metáfases alteradas induzidas pela DXR.

There is considerable interest in identifying dietary compounds which have the capacity to protect against chromosomal aberrations induced by antitumor agents. Fatty acids and their constituents are able to act as free radical scavengers. Doxorubicin (DXR) is an important chemotherapeutic agent, that also induces chromosome aberrations. Rat bone marrow cells treated simultaneously with olive oil (10 ml/kg body weight) and DXR (90 mg/kg body weight) developed significantly fewer chromosomal aberrations and abnormal metaphases than those treated with DXR alone.