Dolores Jiménez-Farfán

Copper compound induces autophagy and apoptosis of glioma cells by reactive oxygen species and jnk activation

BackgroundGlioblastoma multiforme (GBM) is the most aggressive of the primary brain tumors, with a grim prognosis despite intensive treatment. In the past decades, progress in research has not significantly increased overall survival rate.MethodsThe in vitro antineoplastic effect and mechanism of action of Casiopeina III-ia (Cas III-ia), a copper compound, on rat malignant glioma C6 cells was investigated.ResultsCas III-ia significantly inhibited cell proliferation, inducing autophagy and apoptosis, which correlated with the formation of autophagic vacuoles, overexpression of LC3, Beclin 1, Atg 7, Bax and Bid proteins. A decrease was detected in the mitochondrial membrane potential and in the activity of caspase 3 and 8, together with the generation of intracellular reactive oxygen species (ROS) and increased activity of c-jun NH2-terminal kinase (JNK). The presence of 3-methyladenine (as selective autophagy inhibitor) increased the antineoplastic effect of Cas III-ia, while Z-VAD-FMK only showed partial protection from the antineoplastic effect induced by Cas III-ia, and ROS antioxidants (N-acetylcysteine) decreased apoptosis, autophagy and JNK activity. Moreover, the JNK –specific inhibitor SP600125 prevented Cas III-ia-induced cell death.ConclusionsOur data suggest that Cas III-ia induces cell death by autophagy and apoptosis, in part due to the activation of ROS –dependent JNK signaling. These findings support further studies of Cas III-ia as candidate for treatment of human malignant glioma.

Multiple Molecular and Cellular Mechanisms of Action of Lycopene in Cancer Inhibition

Epidemiological studies suggest that including fruits, vegetables, and whole grains in regular dietary intake might prevent and reverse cellular carcinogenesis, reducing the incidence of primary tumours. Bioactive components present in food can simultaneously modulate more than one carcinogenic process, including cancer metabolism, hormonal balance, transcriptional activity, cell-cycle control, apoptosis, inflammation, angiogenesis and metastasis. Some studies have shown an inverse correlation between a diet rich in fruits, vegetables, and carotenoids and a low incidence of different types of cancer. Lycopene, the predominant carotenoid found in tomatoes, exhibits a high antioxidant capacity and has been shown to prevent cancer, as evidenced by clinical trials and studies in cell culture and animal models. In vitro studies have shown that lycopene treatment can selectively arrest cell growth and induce apoptosis in cancer cells without affecting normal cells. In vivo studies have revealed that lycopene treatment inhibits tumour growth in the liver, lung, prostate, breast, and colon. Clinical studies have shown that lycopene protects against prostate cancer. One of the main challenges in cancer prevention is the integration of new molecular findings into clinical practice. Thus, the identification of molecular biomarkers associated with lycopene levels is essential for improving our understanding of the mechanisms underlying its antineoplastic activity.

In vitro evaluation of apoptotic effect of bis(acetylacetonato-k2 O,O′)(1,10-phenanthroline-k2 N,N′)Zn(II) complex

Phenanthroline derivatives have been reported as potential bioactive compounds because of their ability to interact with DNA. To evaluate the antiproliferative effect of bis(acetylacetonate‐k2 O,O)(1,10‐phenanthroline‐k2 N,N)Zn(II) or Zn(acac)2(phen) complex, the compound was obtained in a simple manner and further characterized to determine crystal structure, thermal behavior, morphology, and spectroscopic properties. The structure of the complex was confirmed by X‐ray single structure as well as by 1H and 13C nuclear magnetic resonance (NMR) in dmso‐d6 (dimethyl sulfoxide) solution and in the solid state by 13C CP/MAS. Although preparation of this compound has been described previously, there are no reports on its biological activity; here, we assessed its antiproliferative effect on fibroblasts, A253, FaDu, Cal‐27, RH‐30, RD, U‐373, C6, A‐549, MDA‐MB‐231, and MCF‐7 cancer cell lines at different doses (50–100 and 150 μg/ml). The cell viability was determined by MTT assay and high activity was observed for the most of the cell lines, and TUNEL results showed the induction of apoptosis.