Browsing by Subject "Proliferation"

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Glucocorticoid-induziertes Wachstum von Tumorzellen
systematische Quantifizierung, Signalmechanismen und Inhibition
(2010) Gündisch, Sibylle; Jeremias, Irmela
Glucocorticoids (GCs) like Dexamethasone (Dex) are widely used in cancer patients, as cytotoxic drugs in hematopoetic tumors or adjuvants in solid tumors to reduce severe side effects. Nevertheless, GCs are accused to reduce anti-cancer treatment efficiency. Due to preliminary works in our research group the suspicion arose that GCs are able to induce proliferation of tumor cells. The present work provides the first systematic quantification of the proproliferative effects of GCs on tumor cells. Enhanced tumor cell growth was validated by repetitive microscopy, impedance analysis, investigation of DNA synthesis rate, enzymatic activity as well as absolute cell number. It could be proven that 6 out of 10 cell lines from solid tumors showed enhanced proliferation after stimulation with Dex, whereas this phenotype was not limited to one tumour entity or a common origin. In vivo, Dex significantly promoted tumor cell growth in a preclinical mouse model with a lung carcinoma cell line. Furthermore the effect of GCs was detected on 139 primary, patient-derived acute childhood leukemia cells. In 15% GCs were able to increase the in vitro survival of the tumor cells and one sample showed even GC-induced proliferation. Accordingly the anti-apoptotic and pro-proliferative effects of GCs could be proven not only on established solid tumor cell lines but also on primary hematopoetic tumor cells. Knockdown studies in cells of solid tumors showed that GC-induced proliferation was mediated by the glucocorticoid receptor and was further transmitted by the proteinkinases Akt and p38-MAPK. GC-induced proliferation could be prevented by induction of apoptosis which was caused either by clinically applicable substances, as for example Vincristine, or by inducible expression of the pro-apoptotic molecule Caspase-3. To sum up, the present work identified GC-induced proliferation of tumor cells as a new, tumor cell directed side effect of GCs. Of direct translational relevance, our data argue towards a restricted use of GCs during anti-cancer therapy as well as the need for preclinical and clinical studies which demonstrate a more effective and safer application of GCs during anti-cancer therapy.
Improved satellite cell proliferation induced by L-carnosine benefits muscle growth of pigs in part through activation of the Akt/mTOR/S6K signaling pathway
(2022) Liu, Yaojun; Shen, Wenqiang; Liu, Tao; Mosenthin, Rainer; Bao, Yinghui; Chen, Peng; Hao, Wenbo; Zhao, Lihong; Zhang, Jianyun; Ji, Cheng; Ma, Qiugang
(1) Background: L-carnosine (β-alanyl-L-histidine), a natural dipeptide, exists at relatively high concentrations in skeletal muscles, and has been shown to protect cells from adverse conditions due to its antioxidant, anti-aging, anti-glycation, and buffering properties. Satellite cells (SCs), residing on the myofiber surface, are crucial for muscle post-growth and regeneration. However, the effects of L-carnosine on muscle development of pigs in vivo, on proliferation and growth of SCs in vitro, and the relationship between SCs and muscle development have not yet been investigated. (2) Methods: The objective of this study was to assess the effect of dietary L-carnosine on growth performance and longissimus dorsi muscle development of pigs in vivo, and to elaborate its molecular mechanisms in vitro using L-carnosine-treated SCs. (3) Results: It was shown that L-carnosine supplementation (0.2 and 2 mM) increased (p < 0.05) SC proliferation and cell percentage in the synthesis (S) phase and decreased cell percentage in the resting (G0)/first gap (G1)/phase. Moreover, average daily gain (ADG) of pigs fed diets containing 0.1% of L-carnosine was higher (p < 0.05) than that of pigs fed diets without L-carnosine, and the longissimus dorsi muscle weight of pigs assigned to the L-carnosine treatments was 7.95% higher compared to control pigs. Both in the longissimus dorsi muscle and cultured SCs of pigs, the Akt/mTOR/S6K signaling pathway was activated (p < 0.05), suggesting that L-carnosine improved muscle growth and SC proliferation of pigs. (4) Conclusions: Considering the important role of SCs in post-natal muscle growth, there is evidence that L-carnosine may improve muscle growth of pigs through promoting SC proliferation via activating the Akt/mTOR/S6K signaling pathway.