Resveratrol induced premature senescence and inhibited epithelial-mesenchymal transition of cancer cells via induction of tumor suppressor Rad9

Chen, Kuan‐Yu; Chen, Chao-Chung; Chang, Yi-Chien; Chang, Ming-Chung

doi:10.1371/journal.pone.0219317

Cited by 30 publications

(20 citation statements)

References 47 publications

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“…In many tumors, they are lost or inactivated due to mutation(s), making proteins less effective at controlling cell growth and/or repair. In lung cancer, several tumor suppressor function as biomarkers for metastasis and prognosis, such as Rb, P53, PTEN 33, KAI1/CD82 34, PARK2 35 and Rad9 36. A number of studies have also identified aberrant microRNA expression in cancer.…”

Section: Discussionmentioning

confidence: 99%

βKlotho is identified as a target for theranostics in non-small cell lung cancer

Fan

et al. 2019

Theranostics

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Non-small cell lung cancer (NSCLC) remains a great challenge, calling for the identification of novel molecular targets with diagnostic/therapeutic value. Here, we sought to characterize the expression of βKlotho and its anti-tumor roles in NSCLC.Methods: The expression of βKlotho was examined in NSCLC cells and tissues by western blot, qRT-PCR and immunohistochemistry staining respectively. Biological roles of βKlotho were revealed by a series of functional in vitro and in vivo studies. Serum βKlotho concentrations of patients were measured using specific ELISA methods.Results: Serum βKlotho concentrations of NSCLC patients were significantly lower than the control group. Moreover, βKlotho expression was negatively associated with lymph node metastasis, overall survival and progression-free survival. Overexpression of βKlotho or exogenous βKlotho administration inhibited the proliferation and migration of NSCLC cells, accompanied by induction of apoptosis, G1 to S phase arrest, and inactivation of ERK1/2, AKT and STAT3 signaling. Furthermore, βKlotho overexpression inhibited NSCLC tumor growth in vivo.Conclusions: βKlotho serves as a novel target for theranostics in NSCLC, which has potential clinical applications in the future.

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Section: Discussionmentioning

confidence: 99%

βKlotho is identified as a target for theranostics in non-small cell lung cancer

Fan

et al. 2019

Theranostics

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“…By down-regulation of the snail signaling pathway, resveratrol reduces EMT to inhibit the invasion of colon cancer cells [63]. It is worth mentioning that resveratrol activates tumor suppressor Rad9 to induce premature senescence in lung and breast cancer cells [64]. Another published article also demonstrates the capability of resveratrol in the regulation of epigenetic factors [65].…”

Section: Resveratrol In the Treatment Of Cancermentioning

confidence: 97%

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

et al. 2020

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Mitochondria are intracellular organelles with two distinct membranes, known as an outer mitochondrial membrane and inner cell membrane. Originally, mitochondria have been derived from bacteria. The main function of mitochondria is the production of ATP. However, this important organelle indirectly protects cells by consuming oxygen in the route of energy generation. It has been found that mitochondria are actively involved in the induction of the intrinsic pathways of apoptosis. So, there have been efforts to sustain mitochondrial homeostasis and inhibit its dysfunction. Notably, due to the potential role of mitochondria in the stimulation of apoptosis, this organelle is a promising target in cancer therapy. Resveratrol is a non-flavonoid polyphenol that exhibits significant pharmacological effects such as antioxidant, anti-diabetic, anti-inflammatory and anti-tumor. The anti-tumor activity of resveratrol may be a consequence of its effect on mitochondria. Multiple studies have investigated the relationship between resveratrol and mitochondria, and it has been demonstrated that resveratrol is able to significantly enhance the concentration of reactive oxygen species, leading to the mitochondrial dysfunction and consequently, apoptosis induction. A number of signaling pathways such as sirtuin and NF-κB may contribute to the mitochondrial-mediated apoptosis by resveratrol. Besides, resveratrol shifts cellular metabolism from glycolysis into mitochondrial respiration to induce cellular death in cancer cells. In the present review, we discuss the possible interactions between resveratrol and mitochondria, and its potential application in cancer therapy.

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“…Thus, cells with a mesenchymal phenotype characterized by a lower proliferation index are less sensitive to the cytotoxic effect of chemotherapy compared to those with an epithelial phenotype [ 75 , 106 , 192 , 193 ]. In addition, several recent studies have demonstrated the direct effect of EMT on the well-known mechanisms of tumor cell tolerance to massive DNA damage associated with DNA repair [ 194 , 195 , 196 ], cell-cycle control [ 197 , 198 , 199 ], inactivation of reactive oxygen species [ 200 , 201 ], and autophagy [ 202 ]. Thus, the molecular mechanisms behind the development of resistance to chemotherapy are diverse and, for many types of cancer, mediated by the launch of EMT; however, their relationship remains poorly understood.…”

Section: Emt and Resistance To Antitumor Therapy: Role In The Formatimentioning

confidence: 99%

Epithelial–mesenchymal transition: role in cancer progression and the perspectives of antitumor treatment

et al. 2020

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About 90% of all malignant tumors are of epithelial nature. The epithelial tissue is characterized by a close interconnection between cells through cellcell interactions, as well as a tight connection with the basement membrane, which is responsible for cell polarity. These interactions strictly determine the location of epithelial cells within the body and are seemingly in conflict with the metastatic potential that many cancers possess (the main criteria for highly malignant tumors). Tumor dissemination into vital organs is one of the primary causes of death in patients with cancer. Tumor dissemination is based on the so-called epithelialmesenchymal transition (EMT), a process when epithelial cells are transformed into mesenchymal cells possessing high mobility and migration potential. More and more studies elucidating the role of the EMT in metastasis and other aspects of tumor progression are published each year, thus forming a promising field of cancer research. In this review, we examine the most recent data on the intracellular and extracellular molecular mechanisms that activate EMT and the role they play in various aspects of tumor progression, such as metastasis, apoptotic resistance, and immune evasion, aspects that have usually been attributed exclusively to cancer stem cells (CSCs). In conclusion, we provide a detailed review of the approved and promising drugs for cancer therapy that target the components of the EMT signaling pathways.

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Resveratrol induced premature senescence and inhibited epithelial-mesenchymal transition of cancer cells via induction of tumor suppressor Rad9

Cited by 30 publications

References 47 publications

βKlotho is identified as a target for theranostics in non-small cell lung cancer

βKlotho is identified as a target for theranostics in non-small cell lung cancer

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

Epithelial–mesenchymal transition: role in cancer progression and the perspectives of antitumor treatment

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