Non-cell-autonomous Effects of Autophagy Inhibition in Tumor Cells Promote Growth of Drug-resistant Cells.

Autophagy, the mechanism by which cells deliver material to the lysosome, has been associated with resistance to anticancer drugs, leading autophagy inhibition to be widely studied as a potential chemosensitization strategy for cancer cells. This strategy is based on the idea that inhibition of autophagy will increase drug sensitivity and kill more cancer cells. Here we report an unintended negative effect of this strategy.

Effects of Autoclaving Soy-Free and Soy-Containing Diets for Laboratory Rats on Protein and Energy Values Determined In Vitro and In Vivo.

Autoclaving diminishes the nutritional value of rat diets, depending on the duration and temperature of the process and the type of dietary protein. We evaluated in vivo and in vitro the effects of autoclaving on the protein and energy values of soy-free and soy-containing rat diets. The true digestibility and biological value of the dietary protein were determined in a 10-d experiment involving 28-d-old Wistar Crl:WI(Han) male rats fed casein- or soy-containing diet that was autoclaved for 20 min at 121 °C (T1), 10 min at 134 °C (T2), or not autoclaved (T0).

Growth performance and physiological parameters of conventional and specified pathogen-free rats fed autoclaved diets with different protein sources.

The effects of feeding autoclaved commercial SSNIFF (SN) diet and diets containing soya bean (S) and casein (C) to growing conventional (CON) and specified pathogen-free (SPF) rats were determined. Diets S, C and SN, autoclaved at 121 °C during 20 min (T1), at 134 °C during 10 min (T2) and non-autoclaved (T0), were fed during four weeks, each to 8 CON males and 8 females of mean initial body weight 56 g, kept individually. Diets S, C and SN, autoclaved at T1, were fed during two months, each to 20 SPF males and 20 females of mean initial body weight 58 g, kept in group of 5 animals per cage.

Regulation of autophagy and chloroquine sensitivity by oncogenic RAS in vitro is context-dependent.

Chloroquine (CQ) is an antimalarial drug and late-stage inhibitor of autophagy currently FDA-approved for use in the treatment of rheumatoid arthritis and other autoimmune diseases. Based primarily on its ability to inhibit autophagy, CQ and its derivative, hydroxychloroquine, are currently being investigated as primary or adjuvant therapy in multiple clinical trials for cancer treatment. Oncogenic RAS has previously been shown to regulate autophagic flux, and cancers with high incidence of RAS mutations, such as pancreatic cancer, have been described in the literature as being particularly susceptible to CQ treatment, leading to the hypothesis that oncogenic RAS makes cancer cells dependent on autophagy.

Autophagy controls the kinetics and extent of mitochondrial apoptosis by regulating PUMA levels.

Macroautophagy is thought to protect against apoptosis; however, underlying mechanisms are poorly understood. We examined how autophagy affects canonical death receptor-induced mitochondrial outer membrane permeabilization (MOMP) and apoptosis. MOMP occurs at variable times in a population of cells, and this is delayed by autophagy.