Dual Akt and Bcl-2 inhibition induces cell-type specific modulation of apoptotic and autophagic signaling in castration resistant prostate cancer cell lines.

Background: Cancer cell survival depends on the cross-regulation between apoptosis and autophagy which share common signaling pathways including PI3K/Akt/mTOR and Bcl-2. The aim of this study was to elucidate the modulation patterns between apoptosis and autophagy following dual inhibition by Akt inhibitor erufosine and Bcl-2 inhibitor ABT-737 in castration-resistant prostate cancer (CRPC) cell lines, PC-3 (Bax+) and DU-145 (Bax-).

Methods And Results: Cell cycle progression, apoptotic and autophagic signaling were examined by flow cytometry, multi-caspase assay, Hoechst staining, acridine orange staining of acidic vesicular organelles (AVOs), qRT-PCR and Western Blot.

Multiple Facets of Autophagy and the Emerging Role of Alkylphosphocholines as Autophagy Modulators.

Autophagy is a highly conserved multistep process and functions as passage for degrading and recycling protein aggregates and defective organelles in eukaryotic cells. Based on the nature of these materials, their size and degradation rate, four types of autophagy have been described, chaperone mediated autophagy, microautophagy, macroautophagy, and selective autophagy. One of the major regulators of this process is mTOR, which inhibits the downstream pathway of autophagy following the activation of its complex 1 (mTORC1).

ABT-737 and erufosine combination against castration-resistant prostate cancer: a promising but cell-type specific response associated with the modulation of anti-apoptotic signaling.

A deeper understanding of the molecular basis of castration-resistant prostate cancer (CRPC) paved the way for the rational design and development of targeted therapies, which yielded promising preclinical results. However, translation of these potentially promising agents into clinics has usually failed, partly because of tumor heterogeneity. In this study, anticancer activities of the Bcl-2 inhibitor ABT-737 and the Akt-inhibitor erufosine (ErPC3) alone and in combination were compared between CRPC (PC-3 and DU-145) and healthy (PNT-1A) cell lines.

Alkylphospholipids are Signal Transduction Modulators with Potential for Anticancer Therapy.

Background: Alkylphospholipids (APLs) are synthetically derived from cell membrane components, which they target and thus modify cellular signalling and cause diverse effects. This study reviews the mechanism of action of anticancer, antiprotozoal, antibacterial and antiviral activities of ALPs, as well as their clinical use.

Methods: A literature search was used as the basis of this review.

Statin-induced calcific Achilles tendinopathy in rats: comparison of biomechanical and histopathological effects of simvastatin, atorvastatin and rosuvastatin.

Purpose: Accumulating clinical evidence indicates the risk of tendinopathy and spontaneous and/or simultaneous tendon ruptures associated with statin use. This experimental study was designed to evaluate and compare the biomechanical and histopathological effects of the three most commonly prescribed statins (simvastatin, atorvastatin and rosuvastatin) on the Achilles tendon in rats.

Methods: Statins were administered by gavage to rats at daily doses of 20 and 40 mg/kg for 3 weeks.

SIBLINGs and SPARC families: their emerging roles in pancreatic cancer.

Pancreatic cancer has a considerably poor prognosis with a 5-year survival probability of less than 5% when all stages are combined. Pancreatic cancer is characterized by its dense stroma, which is involved in the critical interplay with the tumor cells throughout tumor progression and furthermore, creates a barrier restricting efficient penetration of therapeutics. Alterations in a large number of genes are reflected by a limited number of signaling pathways, which are potential targets.

Differential effects of erufosine on proliferation, wound healing and apoptosis in colorectal cancer cell lines.

The alkylphosphocholine, erucylphospho-N,N, N-trimethylpropanolamine (erufosine), has demonstrated anticancer effects in various cell lines, including leukemia, multiple myeloma, bladder, breast and oral squamous cell carcinoma cells. The purpose of the present study was to investigate its antiproliferative, antimigratory and pro-apoptotic effects in colorectal cancer cell lines, SW480 and CC531. The antiproliferative effect was determined by (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) (MTT) dye reduction assay following exposure to erufosine (3.

Fluoroquinolone-induced tendinopathy: etiology and preventive measures.

Tendinopathy is a serious health problem and its etiology is not fully elucidated. Among intrinsic and extrinsic predisposing factors of tendinopathy, the impact of therapeutic agents, especially fluoroquinolone (FQ) group antibiotics, is recently being recognized. FQs are potent bactericidal agents widely used in various infectious diseases, including community acquired pneumonia and bronchitis, chronic osteomyelitis, traveler's diarrhea, typhoid fever, shigellosis, chronic bacterial prostatitis, uncomplicated cervical and urethral gonorrhea and prophylaxis of anthrax.

Oral toxicity of pefloxacin, norfloxacin, ofloxacin and ciprofloxacin: comparison of biomechanical and histopathological effects on Achilles tendon in rats.

Four fluoroquinolones (pefloxacin, norfloxacin, ofloxacin and ciprofloxacin) were compared according to their biomechanical and histopathological effects on rat Achilles tendon. Wistar rats were divided into one untreated control and four treatment groups in parallel. Pefloxacin mesylate dihydrate (40 mg/kg), norfloxacin (40 mg/kg), ofloxacin (20 mg/kg) and ciprofloxacin (50 mg/kg) were administered by gavage twice daily for three consecutive weeks.