Three-dimensional structure of human cyclooxygenase (hCOX)-1.

The beneficial effects of Cyclooxygenases (COX) inhibitors on human health have been known for thousands of years. Nevertheless, COXs, particularly COX-1, have been linked to a plethora of human diseases such as cancer, heart failure, neurological and neurodegenerative diseases only recently. COXs catalyze the first step in the biosynthesis of prostaglandins (PGs) and are among the most important mediators of inflammation.

UCN-01 enhances cytotoxicity of irinotecan in colorectal cancer stem-like cells by impairing DNA damage response.

Colorectal cancer (CRC) is one of the most common and lethal cancers worldwide. Despite recent progress, the prognosis of advanced stage CRC remains poor, mainly because of cancer recurrence and metastasis. The high morbidity and mortality of CRC has been recently ascribed to a small population of tumor cells that hold the potential of tumor initiation, i.

High nitric oxide production, secondary to inducible nitric oxide synthase expression, is essential for regulation of the tumour-initiating properties of colon cancer stem cells.

Chronic inflammation is a leading cause of neoplastic transformation in many human cancers and especially in colon cancer (CC), in part due to tumour promotion by nitric oxide (NO) generated at inflammatory sites. It has also been suggested that high NO synthesis, secondary to inducible NO synthase (iNOS) expression, is a distinctive feature of cancer stem cells (CSCs), a small subset of tumour cells with self-renewal capacity. In this study we explored the contribution of NO to the development of colon CSC features and evaluated potential strategies to treat CC by modulating NO production.

(1) H NMR spectroscopy of glioblastoma stem-like cells identifies alpha-aminoadipate as a marker of tumor aggressiveness.

Patients suffering from glioblastoma multiforme (GBM) face a poor prognosis with median survival of about 14 months. High recurrence rate and failure of conventional treatments are attributed to the presence of GBM cells with stem-like properties (GSCs). Metabolite profiles of 42 GSC lines established from the tumor tissue of adult GBM patients were screened with (1) H NMR spectroscopy and compared with human neural progenitor cells from human adult olfactory bulb (OB-NPCs) and from the developing human brain (HNPCs).

Blocking p38/ERK crosstalk affects colorectal cancer growth by inducing apoptosis in vitro and in preclinical mouse models.

We recently demonstrated that p38α is required to maintain colorectal cancer (CRC) metabolism, as its inhibition leads to FoxO3A activation, autophagy, cell death, and tumor growth reduction both in vitro and in vivo. Here we show that inhibition of p38α is followed by TRAIL-mediated activation of caspase-8 and FoxO3A-dependent HER3 upregulation with consequent overactivation of the MEK-ERK1/2 survival pathway. p38α and MEK combined inhibition specifically induces apoptosis by enabling TRAIL signaling propagation through t-Bid and caspase-3, and fosters cell death in CRC cells and preclinical mouse models.

p38alpha is required for ovarian cancer cell metabolism and survival.

Introduction: Ovarian cancer is highly sensitive to chemotherapy but also shows a high rate of recurrence and drug resistance. These negative outcomes mostly depend on altered apoptotic pathways, making the design of new therapeutic strategies based on the induction of other types of cell death highly desirable. Several lines of research are now addressing cancer-specific features to specifically target tumor cells, thus reducing adverse effects.