Epigallocatechin gallate suppresses premature senescence of preadipocytes by inhibition of PI3K/Akt/mTOR pathway and induces senescent cell death by regulation of Bax/Bcl-2 pathway

Kumar, Ravi; Sharma, Anamika; Kumari, Amita; Gulati, Ashu; Padwad, Yogendra; Sharma, Rohit

doi:10.1007/s10522-018-9785-1

Cited by 92 publications

(52 citation statements)

References 36 publications

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“…In accordance with that, we conducted Western blot to assess whether the AKT/mTOR signaling pathway is involved in the regulation of ESCO2 in RCC progression and the results concluded our hypothesis. In addition, p53 has been reported as a major tumor suppressor, cooperating with the AKT/mTOR pathway . The exertion of ESCO2 functions relied on the protein‐protein bindings, such as p53 and SMC3 .…”

Section: Discussionmentioning

confidence: 99%

Establishment of cohesion 1 homolog 2 facilitates cell aggressive behaviors and induces poor prognosis in renal cell carcinoma

Wang

Liu

2020

Clinical Laboratory Analysis

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Background and aims Establishment of cohesion 1 homolog 2 (ESCO2) has been identified as an essential factor for cohesion in cell cycle in human multiple cancers. Nonetheless, its functional implication on prognosis and cellular behaviors of renal cell carcinoma (RCC) is rarely elucidated. We performed this study to detect the effects of ESCO2 in RCC progression. Methods We accessed The Cancer Genome Atlas (TCGA) database to evaluate the ESCO2 expression levels in tumor tissues, including 32 normal tissues and 289 tumor tissues. Quantitative real‐time PCR and Western blot were implemented for expression detection. After ESCO2 knockdown using siRNAs interference, functional experiments were conducted to explore the role of ESCO2, such as cell proliferation analysis and colony formation assay. Transwell assays for migration and invasion was also performed. Results In this study, ESCO2 was significantly increased in RCC tissues and cell lines. The RCC patients with high expression of ESCO2 were susceptible to unfavorable prognosis, and its expression has a marked association with clinical features containing age, gender, pathologic stage, and so on. Furthermore, knockdown of ESCO2 inhibited cell growth, invasion, and migration. Mechanistically, phosphorylation protein kinase B (AKT) and mammalian target of rapamycin (mTOR), proliferating cell nuclear antigen (PCNA), and p53 were all down‐regulated due to the ESCO2 inhibition. Conclusions Therefore, our results raised the possibility that ESCO2 may act as a promising option for tumor therapeutic interference by exhibiting enhanced selectivity over conventional chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Establishment of cohesion 1 homolog 2 facilitates cell aggressive behaviors and induces poor prognosis in renal cell carcinoma

Wang

Liu

2020

Clinical Laboratory Analysis

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“…Piperlongumine -Radiation-induced senescent astrocytes in vivo -Radiation-induced cognitive dysfunction mouse model [205] -SMARCB1 downregulation-induced senescent A375 melanoma cells -Therapy-induced A549 or H358 lung cancer cells [145] -Radiation-induced, replication exhausted and Ras-induced senescent WI38 fibroblasts [206] Curcumin -Patient-derived senescent intervertebral disc cells [207] -Radiation-induced, oncogene-induced and replication-exhausted senescent WI38 fibroblasts [208] Fisetin -Replication-exhausted senescent Ercc1−/− MEFs -Therapy-induced senescent IMR90 senescent cells -Progeroid Ercc1 −/∆ mice and aged C57BL/6 mouse models -Murine and human-derived senescent adipose tissue [209] -Senescent human umbilical vein endothelial cells [210] Metformin -Murine olfactory ensheathing cells ex vivo [211] Panobinostat -Therapy-induced senescent A549 lung and FaDu head and neck cancer cells [212] 17-DMAG -Oxidative-stress-induce primary Ercc1 −/− -progeroid Ercc1 −/∆ mouse model [213] Torin 1 -Murine senescent hepatocytes ex vivo [214] Epigallocatechin gallate (EGCG) -Senescent 3T3-L1 preadipocytes [215] Bafilomycin A1 -Therapy-induced HCT116 colorectal cancer cells [158] Azithromycin and roxithromycin -Therapy-induced senescent MRC-5 and BJ human fibroblasts [216] Fenofibrate -Senescent T/C28a2 human chondrocytes [217] Cardiac glycosides -Therapy-induced senescent A549 lung cancer cells and SK-MEL-103 melanoma cells in vitro and in vivo [218,219] Several natural and synthetic compounds have been tested for their senescence-eliminating effects in a variety of disease models. The table summarizes the primary current preclinical evidence demonstrating the senolytic agent and the experimental model used.…”

Section: Senolytic Model/cell Line Referencementioning

confidence: 99%

“…The use of rapamycin, which is also an autophagy inducer, has been established as a potent inhibitor of SASP via interfering with mTOR regulation of protein synthesis [136,138]. In addition, a recent report revealed that the phytochemical, epigallocatechin gallate (EGCG), can selectively eliminate senescent 3T3-L1 preadipocytes by downregulating PI3K/Akt/mTOR and AMPK pathways, which are important signaling pathways involved in autophagy induction and regulation, and interfering with the antiapoptotic activity of Bcl-2 [215]. Finally, consistent with the other observations, interference with mTOR function also attenuated SASP [215].…”

Section: Autophagy Modulatorsmentioning

confidence: 99%

Therapy-Induced Senescence: An “Old” Friend Becomes the Enemy

Saleh

Bloukh

Carpenter

et al. 2020

Cancers

194

150

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For the past two decades, cellular senescence has been recognized as a central component of the tumor cell response to chemotherapy and radiation. Traditionally, this form of senescence, termed Therapy-Induced Senescence (TIS), was linked to extensive nuclear damage precipitated by classical genotoxic chemotherapy. However, a number of other forms of therapy have also been shown to induce senescence in tumor cells independently of direct genomic damage. This review attempts to provide a comprehensive summary of both conventional and targeted anticancer therapeutics that have been shown to induce senescence in vitro and in vivo. Still, the utility of promoting senescence as a therapeutic endpoint remains under debate. Since senescence represents a durable form of growth arrest, it might be argued that senescence is a desirable outcome of cancer therapy. However, accumulating evidence suggesting that cells have the capacity to escape from TIS would support an alternative conclusion, that senescence provides an avenue whereby tumor cells can evade the potentially lethal action of anticancer drugs, allowing the cells to enter a temporary state of dormancy that eventually facilitates disease recurrence, often in a more aggressive state. Furthermore, TIS is now strongly connected to tumor cell remodeling, potentially to tumor dormancy, acquiring more ominous malignant phenotypes and accounts for several untoward adverse effects of cancer therapy. Here, we argue that senescence represents a barrier to effective anticancer treatment, and discuss the emerging efforts to identify and exploit agents with senolytic properties as a strategy for elimination of the persistent residual surviving tumor cell population, with the goal of mitigating the tumor-promoting influence of the senescent cells and to thereby reduce the likelihood of cancer relapse.

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“…EGCG was found to suppress premature senescence in preadipocytes, with treated cells showing significant downregulation of ROS, SASP and p53 mediated cell cycle arrest, in addition to the suppression of the anti-apoptotic protein BCL-2 and an increase in cell death (Kumar et al, 2018). This suggests that EGCG could have senolytic properties.…”

Section: Green Tea Catechinsmentioning

confidence: 93%

An Appraisal on the Value of Using Nutraceutical Based Senolytics and Senostatics in Aging

Kaur

Macip

Stover

2020

Front. Cell Dev. Biol.

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The average human life expectancy has increased globally, and continues to rise, owing to the substantive progress made in healthcare, medicine, sanitation, housing and education. This ultimately enriches society with a greater proportion of elderly people. Sustaining a healthy aged population is key to diminish the societal and economic impact of age-related infirmities. This is especially challenging because tissue function, and thus wellbeing, naturally progressively decline as humans age. With age increasing the risk of developing diseases, one of the therapeutic options is to interfere with the molecular and cellular pathways involved in age-related tissue dysfunction, which is in part caused by the accumulation of senescent cells. One strategy to prevent this could be using drugs that selectively kill these cells (senolytics). In parallel, some compounds have been identified that prevent or slow down the progression of senescence or some of its features (senostatics). Senolytic and senostatic therapies have been shown to be efficient in vivo, but they also have unwanted dose-dependent side effects, including toxicity. Important advances might be made using bioactive compounds from plants and foods (nutraceuticals) if, as is proposed, they offer similar effectiveness with fewer side effects. The focus of this review is on the use of nutraceuticals in interfering with cellular senescence.

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Epigallocatechin gallate suppresses premature senescence of preadipocytes by inhibition of PI3K/Akt/mTOR pathway and induces senescent cell death by regulation of Bax/Bcl-2 pathway

Cited by 92 publications

References 36 publications

Establishment of cohesion 1 homolog 2 facilitates cell aggressive behaviors and induces poor prognosis in renal cell carcinoma

Establishment of cohesion 1 homolog 2 facilitates cell aggressive behaviors and induces poor prognosis in renal cell carcinoma

Therapy-Induced Senescence: An “Old” Friend Becomes the Enemy

An Appraisal on the Value of Using Nutraceutical Based Senolytics and Senostatics in Aging

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