Resveratrol delays replicative senescence of human mesothelial cells via mobilization of antioxidative and DNA repair mechanisms

Mikuła-Pietrasik, Justyna; Kuczmarska, Angelika; Rubiś, Błażej; Filas, Violetta; Murias, Marek; Zieliński, Paweł; Piwocka, Katarzyna; Książek, Krzysztof

doi:10.1016/j.freeradbiomed.2012.03.014

Cited by 50 publications

(36 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Resveratrol is also reported as a promising molecule for lifespan extension in multiple model organisms, health promotion and disease amelioration in mammals through activation of SIRT1 signaling 63. In addition, resveratrol also delays cell replicative senescence and promotes the osteogenesis of MSCs 64, 65. Quercetin is a well-known ROS scavenger and a regulator of stem cell function 66, 67.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Treatment Improves Mesenchymal Stem Cells Therapy by Preserving Stemness during Long-term In Vitro Expansion

et al. 2016

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of MSCs, resulting in failure of MSCs therapy. Here, we report a melatonin-based strategy to improve cell therapy of in vitro cultured MSCs. Among four small molecules with anti-aging and stem cell-protection properties (rapamycin, resveratrol, quercetin and melatonin), colony forming, proliferation, and osteogenic differentiation assay showed that melatonin was the most efficient to preserve self-renewal and differentiation properties of rat bone marrow MSCs (BMMSCs) after long-term passaging. Functional assays confirmed melatonin treatment did not affect the colony forming, proliferation and osteogenic differentiation of BMMSCs cultured for 1 or 4 passages, but largely prevented the decline of self-renew and differentiation capacity of BMMSCs cultured for 15 passages in vitro. Furthermore, heterotopic osteogenesis assay, critical size calvarial defects repair assay, osteoporosis treatment and experimental colitis therapy assay strongly certified that melatonin preserved the therapeutic effect of long-term passaged BMMSCs on bone regeneration and immunotherapy in vivo. Mechanistically, melatonin functioned by activating antioxidant defense system, inhibiting the pathway of cell senescence, and preserving the expression of gene governing the stemness. Taken together, our findings showed that melatonin treatment efficiently prevented the dysfunction and therapeutic failure of BMMSCs after long-term passaging, providing a practical strategy to improve the application of BMMSCs in tissue engineering and cytotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Melatonin Treatment Improves Mesenchymal Stem Cells Therapy by Preserving Stemness during Long-term In Vitro Expansion

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Altogether, our data show that blocking telomerase activity can be used as an effective way to induce death of breast cancer cells. We analyzed the telomere length (according to a protocol previously described in [36 ] and we observed that TERT siRNA treatment did not provoke significant telomere length change after 72 h of exposure (however, slight but not significant shortening was observed, data not shown). Thus, it may be that treatment of cancer patients with telomerase inhibitors does not have to be a long-term treatment and does not have to depend directly on replicative senescence and telomere length.…”

Section: Discussionmentioning

confidence: 99%

Telomerase downregulation induces proapoptotic genes expression and initializes breast cancer cells apoptosis followed by DNA fragmentation in a cell type dependent manner

et al. 2013

View full text Add to dashboard Cite

The aim of the study was to analyze the consequence of silencing genes coding for the key subunits of the telomerase complex, i.e. TERT, TERC and TP1 in human breast cancer MCF7 and MDA-MB-231cells. The transfection was performed using Lipofectamine2000 and pooled siRNAs. The cytotoxic and/or antiproliferative effect of siRNA was measured by the SRB assay, the cell cycle was analysed by flow cytometry and DNA fragmentation by TUNEL analysis. Telomerase activity was assessed by TRAP, followed by PAGE and ELISA assays. Telomerase downregulation was also assessed using qPCR in order to estimate the changes in the expression profile of genes engaged in apoptosis. It was revealed that treatment of breast cancer cells with different siRNAs (100 nM) resulted in a cell type and time-dependent effects. The downregulation of telomerase subunits was followed by reduction of telomerase activity down to almost 60 % compared to control cells. However, a significant effect was only observed when the TERT subunit was downregulated. Its silencing resulted in a significant (p < 0.05) increase of apoptosis (over 10 % in MCF7 and about 5 % in MDA-MB-231 cells, corresponding to the Annexin V assay) and DNA fragmentation (almost 30 % in MCF7 and over 25 % in MDA-MB-231 cells). Interestingly, also several proapoptotic genes were induced after the downregulation of the key telomerase subunit, including Bax, Bik or caspase-1 and caspase-14, as well as NGFR and TNFSF10 which were upregulated twice and more.

show abstract

“…The radioactivity that was released was measured in a beta liquid scintillation counter (LKB Wallac, Turku, Finland). The results were expressed as counts per minute (cpm) [10]. In some experiments, cancer cell proliferation was examined in response to exogenous recombinant GRO-1, IL-6 and IL-8 or in the presence of specific neutralizing antibodies against these agents.…”

Section: Adhesion and Proliferation Measurementsmentioning

confidence: 99%

Peritoneal mesothelium promotes the progression of ovarian cancer cells in vitro and in a mice xenograft model in vivo

et al. 2014

Self Cite

View full text Add to dashboard Cite

Resveratrol delays replicative senescence of human mesothelial cells via mobilization of antioxidative and DNA repair mechanisms

Cited by 50 publications

References 45 publications

Melatonin Treatment Improves Mesenchymal Stem Cells Therapy by Preserving Stemness during Long-term In Vitro Expansion

Melatonin Treatment Improves Mesenchymal Stem Cells Therapy by Preserving Stemness during Long-term In Vitro Expansion

Telomerase downregulation induces proapoptotic genes expression and initializes breast cancer cells apoptosis followed by DNA fragmentation in a cell type dependent manner

Peritoneal mesothelium promotes the progression of ovarian cancer cells in vitro and in a mice xenograft model in vivo

Contact Info

Product

Resources

About