Cynaropicrin, a sesquiterpene lactone, triggers apoptotic cell death in triple negative breast cancer cells.

BACKGROUND: Breast cancer is the most common cancer in the world. Cynaropicrin is a natural sesquiterpene lactone with potential anticancer effects. The present study was conducted to evaluate the effect of cynaropicrin on proliferation and apoptosis in breast cancer cells. METHODS: MDA-MB-231 and MCF-7 cell lines were treated with increasing concentrations of cynaropicrin. The viability of both cell lines was measured using MTT assay. Flowcytometry was used to detect apoptotic cells. The expression levels of apoptosis-related genes were determined using quantitative polymerase chain reaction. The protein expression of apoptosis markers was determined by western blotting. RESULTS: Cynaropicrin significantly diminished the proliferation of MDA-MB-231 and MCF-7 cell lines in a dose-dependent manner. Flowcytometry data uncovered that cynaropicrin augmented early and late apoptosis in MDA-MB-231 cells. Real time-PCR and western blotting results also confirmed the upregulation of pro-apoptotic Bax, caspase-3, -8, and 9 as well as downregulated level of anti-apoptotic marker Bcl-2. Cynaropicrin also remarkably increased the activity of caspase-3, -8, and 9 in MDA-MB-231 cells. However, cynaropicrin neither promoted apoptosis in MCF-7 cells nor altered the expression levels and activity of above mentioned apoptotic markers. CONCLUSION: The present data indicated anti-proliferative properties of cynaropicrin against breast cancer and highlighted apoptosis-inducing effects of this sesquiterpene on triple negative breast cancer (TNBC) cells. These data may suggest cynaropicrin as a potential anti-TNBC agent to tackle therapy resistance in this type of breast cancer.

Experimental evidence of the neurotoxic effect of monosodium glutamate in adult female Sprague Dawley rats: The potential protective role of Zingiber officinale Rosc. rhizomes.

Strategies to prevent the health abnormalities associated with the extensive use of MSG (monosodium glutamate) as a flavoring booster are badly needed. The current study was conducted to investigate oxidative stress, inflammation, and abnormal lipid profile as the main risk factors of neurotoxicity in MSG-exposed female albino rats. Besides, the effect of concurrent consumption of Zingiber officinale rhizomes powder was studied at low doses. Twenty rats (total) were split into 4 separate groups. The 1st group was a negative control group (without any treatment), while the others received 6 mg MSG/kg. The 2nd group was left untreated, whereas the 3rd and 4th groups were given a regular laboratory diet that included ginger rhizome powder supplements (GRP, 0.5 & 1%, respectively) for six weeks. In brain tissue homogenates, exposure to MSG caused a significant depletion of gamma-aminobutyric acid (GABA) and total protein levels, while triglycerides and cholesterol contents were significantly elevated. Moreover, a noteworthy upsurge in oxidative load and inflammation markers was also noticed associated with a marked reduction of antioxidant levels, which histopathological staining verified further. The rat diet formulated with GRP, with a dose-dependent effect, resulted in increased GABA and total protein contents and attenuated inflammation, oxidative stress, abnormal lipid profile, and marked histological changes in cerebral cortical neurons of MSG-administered animals. Therefore, this study reveals that GRP shields rats against the neurotoxicity that MSG causes. The anti-inflammatory as well as antioxidant, and lipid-normalizing properties of rhizomes of ginger may be accountable for their observed neuroprotective action.

CDC2-like (CLK) protein kinase inhibition as a novel targeted therapeutic strategy in prostate cancer.

Dysregulation of alternative splicing is a feature of cancer, both in aetiology and progression. It occurs because of mutations in splice sites or sites that regulate splicing, or because of the altered expression and activity of splice factors and of splice factor kinases that regulate splice factor activity. Recently the CDC2-like kinases (CLKs) have attracted attention due to their increasing involvement in cancer. We measured the effect of the CLK inhibitor, the benzothiazole TG003, on two prostate cancer cell lines. TG003 reduced cell proliferation and increased apoptosis in PC3 and DU145 cells. Conversely, the overexpression of CLK1 in PC3 cells prevented TG003 from reducing cell proliferation. TG003 slowed scratch closure and reduced cell migration and invasion in a transwell assay. TG003 decisively inhibited the growth of a PC3 cell line xenograft in nude mice. We performed a transcriptomic analysis of cells treated with TG003. We report widespread and consistent changes in alternative splicing of cancer-associated genes including CENPE, ESCO2, CKAP2, MELK, ASPH and CD164 in both HeLa and PC3 cells. Together these findings suggest that targeting CLKs will provide novel therapeutic opportunities in prostate cancer.