Survivin antagonizes chemotherapy-induced cell death of colorectal cancer cells.

Irinotecan (CPT-11) and oxaliplatin (L-OHP) are among the most frequently used drugs against colorectal tumors. Therefore, it is important to define the molecular mechanisms that these agents modulate in colon cancer cells. Here we demonstrate that CPT-11 stalls such cells in the G/M phase of the cell cycle, induces an accumulation of the tumor suppressor p53, the replicative stress/DNA damage marker γH2AX, phosphorylation of the checkpoint kinases ATM and ATR, and an ATR-dependent accumulation of the pro-survival molecule survivin.

Class I histone deacetylases regulate p53/NF-κB crosstalk in cancer cells.

The transcription factors NF-κB and p53 as well as their crosstalk determine the fate of tumor cells upon therapeutic interventions. Replicative stress and cytokines promote signaling cascades that lead to the co-regulation of p53 and NF-κB. Consequently, nuclear p53/NF-κB signaling complexes activate NF-κB-dependent survival genes.

Survivin and YM155: how faithful is the liaison?

Survivin belongs to the family of apoptosis inhibitors (IAPs), which antagonizes the induction of cell death. Dysregulated expression of IAPs is frequently observed in cancers, and the high levels of survivin in tumors compared to normal adult tissues make it an attractive target for pharmacological interventions. The small imidazolium-based compound YM155 has recently been reported to block the expression of survivin via inhibition of the survivin promoter.

The endogenous melatonin (MT) signal facilitates reentrainment of the circadian system to light-induced phase advances by acting upon MT2 receptors.

The indolamine melatonin is an important rhythmic endocrine signal in the circadian system. Exogenous melatonin can entrain circadian rhythms in physiology and behavior, but the role of endogenous melatonin and the two membrane-bound melatonin receptor types, MT1 and MT2, in reentrainment of daily rhythms to light-induced phase shifts is not understood. The present study analyzed locomotor activity rhythms and clock protein levels in the suprachiasmatic nuclei (SCN) of melatonin-deficient (C57BL/6J) and melatonin-proficient (C3H/HeN) mice, as well as in melatonin-proficient (C3H/HeN) mice with targeted deletion of the MT1, MT2, or both receptors, to determine effects associated with phase delays or phase advances of the light/dark (LD) cycle.