TNF-α exerts cytotoxic effects on multidrug resistant breast cancer MCF-7/MX cells via a non-apoptotic death pathway.

Tumor necrosis factor-α (TNF-α) is a cytokine involved in the various physiopathological processes such as autoimmune disorders and inflammation related diseases. Some multidrug resistant (MDR) cancer cell lines including MCF-7/MX are more vulnerable to cytotoxic effects of TNF-α than their parental lines. In this study, breast cancer cell line MCF-7 and its MDR derivative MCF-7/MX were exposed to TNF-α afterward various downstream signaling mediators of TNF-α were analyzed. Although, treatment of MCF-7 cells with TNF-α activated NF-kB and caused RIP1 ubiquitination, TNF-α exposure led to JNK and RIP1 phosphorylation in MCF-7/MX cells. In both cell lines TNF-α did not activate the caspase cascade. Moreover, AnexinV/PI analysis showed that cytotoxic effects of TNF-α on MCF-7/MX is mediated via apoptosis independent mechanisms and inhibition of RIP1 kinase activity using necrostatin-1 revealed that kinase activity of RIP1 plays role in the production of ROS, activation of JNK and cellular death following exposure of MCF-7/MX cells to TNF-α. Overall, it seems that RIP1 ubiquitination and NF-kB activation are prosurvival signaling mediators protecting MCF-7 cells against cytotoxic effects of TNF-α while TNF-α drives MCF-7/MX cells to non-apoptotic cellular death via kinase activity of RIP1, activation of JNK and ROS production.

Evaluation of the Cytotoxic Activity of Crocin and Safranal, Constituents of Saffron, in Oral Squamous Cell Carcinoma (KB Cell Line).

Crocin and safranal are active ingredients in the saffron. Some studies have demonstrated antitumor activities of saffron ingredients. The aim of this study was to evaluate cytotoxic effects of crocin and safranal in oral squamous cell carcinoma (KB cells) and NIH 3T3 cell line as nonmalignant cells. The cells were incubated with crocin and safranal at 37°C for 24, 48, and 72 h, and cell viability was quantitated by MTT assay. Apoptotic cells, cell cycle distribution, and sub-G1 fraction were determined using propidium iodide staining of DNA fragmentation by flow cytometry. Crocin (0.05-4 mM) and safranal (0.2-3.2 mM) significantly inhibited the growth of KB cells (the inhibitory growth effects of all concentrations for both were >50% after 72 h), while they had less inhibitory effects on NIH 3T3 cells viability. The IC50 values of crocin and safranal against NIH 3T3 cells after 72 h were determined as 2.8 and 0.3 mM, respectively. Crocin and safranal induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that apoptotic cell death is involved in the toxicity of crocin and safranal. Apoptotic effects of crocin and safranal in tumor cells were more than normal cells. Neither crocin nor safranal affected the cell cycle progression. Crocin and safranal exerted apoptotic effects in KB cell line.

Protective effects of Scutellaria lindbergii root extract against oxidative-induced cell and DNA damage in mouse fibroblast-like cells.

CONTEXT: Scutellaria lindbergii Rech. f. (Lamiaceae) is an Iranian species of Scutellaria which has been shown to exert antimicrobial, antioxidant and cytotoxic effects. OBJECTIVE: The protective properties of total methanol extract (TME) of S. lindbergii and its fractions (defatted and CH2Cl2) were investigated against cytotoxic and genotoxic effects of H2O2 in NIH 3T3 cell line as non-malignant cells. MATERIALS AND METHODS: The cells were incubated with different concentrations of S. lindbergii root extracts [TME (15-250 µg ml(-)(1)), defatted fraction (15-500 µg ml(-)(1)) and CH2Cl2 fraction (5-40 µg ml(-)(1))] and toxic concentration of H2O2 (200 µM) at 37 °C for 2 h concurrently and Cell viability was quantitated by MTT assay. The antigenotoxic effect of extracts was investigated using comet assay. The cells were incubated with extracts [TME (25-250 µg ml(-)(1)), defatted fraction (25-500 µg ml(-)(1)) and CH2Cl2 fraction (5-40 µg ml(-)(1))] and H2O2 (25 µM) at 4 °C for 20 min, then the comet assay was performed. DNA damage was expressed as percentage tail DNA. RESULTS: Total methanol extract of S. lindbergii and its fractions had a significant inhibitory effect on DNA damage. The IC50 values of TME, defatted fraction and CH2Cl2 fraction against DNA damage were determined as 48, 138 and 8 µg ml(-)(1), respectively. CONCLUSION: S. lindbergii extracts can prevent oxidative DNA damage, which is likely due to its flavonoids and phenolic compounds as antioxidant constituents.