scholarly journals Role of Resveratrol as Radiosensitizer by Targeting Cancer Stem Cells in Radioresistant Prostate Cancer Cells (PC-3)

2021 ◽  
Vol 22 (12) ◽  
pp. 3823-3837
Author(s):  
Sanaa A El-Benhawy ◽  
Mohmed I Morsi ◽  
Enayat I Fahmy ◽  
Moustafa A Soula ◽  
Fatma Al Khalil ◽  
...  
2020 ◽  
Author(s):  
Rodrigo Peña-Hernández ◽  
Rossana Aprigliano ◽  
Sandra Frommel ◽  
Karolina Pietrzak ◽  
Seraina Steiger ◽  
...  

AbstractProstate cancer (PCa) is one of the most prevalent cancers in men. Cancer stem cells are thought to be associated with PCa relapse and represent a target against metastatic PCa. Here we show that BAZ2A (also known as TIP5), a factor previously implicated in aggressive PCa, is required for the dedifferentiation of PCa cells into a cancer stem-like state. We found that BAZ2A genomic occupancy in PCa cells coincides with H3K14ac enriched chromatin regions. This association is mediated by BAZ2A bromodomain (BAZ2A-BRD) that specifically binds to H3K14ac. In PCa cells, BAZ2A-BRD is required for the interaction with a class of inactive enhancers that are marked by H3K14ac and represses transcription of genes implicated in developmental and differentiation processes that are frequently silenced in aggressive and dedifferentiated PCa. BAZ2A-mediated repression of these genes is also linked to the histone acetyltransferase EP300 that acetylates H3K14ac. Mutations of BAZ2A-BRD or treatment with chemical probes that abrogate BAZ2A-BRD association with H3K14ac impair the dedifferentiation of PCa cells into a stem-like state. Furthermore, pharmacological inactivation of BAZ2A-BRD impairs the oncogenic transformation mediated by Pten-loss in prostate organoids. Our findings indicate a role of BAZ2A-BRD in PCa stem cell features and suggest potential epigenetic-reader therapeutic strategies to target BAZ2A in aggressive PCa.


2019 ◽  
Vol 60 (3) ◽  
pp. 298-307 ◽  
Author(s):  
Ryo Saga ◽  
Yusuke Matsuya ◽  
Rei Takahashi ◽  
Kazuki Hasegawa ◽  
Hiroyuki Date ◽  
...  

BMC Cancer ◽  
2013 ◽  
Vol 13 (1) ◽  
Author(s):  
Xinlan Fan ◽  
Xu Chen ◽  
Weixi Deng ◽  
Guangzheng Zhong ◽  
Qingqing Cai ◽  
...  

Author(s):  
Guanqun Ju ◽  
Yingjian Zhu ◽  
Tao Du ◽  
Wanli Cao ◽  
Jianhai Lin ◽  
...  

Prostate cancer is one of the most severe male malignant tumors, which ranks second in mortality rate among all tumors. Traditional methods of treatment for prostate cancer produce obvious side effects and a high recurrence rate. Cancer stem cells are considered to be a group of cells that determine the proliferation, metastasis, and drug resistance of tumor. Prostate cancer therapy based on microRNAs and prostate cancer stem cells (PCSCs) has been a research hot spot in this field. Previous studies have reported that miR-197 plays an important role in the occurrence and development of prostate cancer, but the molecular mechanism of miR-197 on the development of prostate cancer has not been reported yet. In this study, we verified that miR-197 is significantly overexpressed in prostate cancer tissues and prostate cancer cells. Then, we verified that miR-197 expression affects the proliferation, invasion, and metastasis of prostate cancer cells by regulating integrin subunit alpha V (ITGAV) expression through STAT5 pathway, and the results indicated that the miR-197 inhibitor can be a prostate cancer suppressor. Then we synthesized the AbCD133@GNR@MSNs@miR-197 inhibitor drug carrier, in which 35.42 μg of the miR-197 inhibitor could be loaded in 1 mg of AbCD133@GNR@MSNs. The AbCD133@GNR@MSNs@miR-197 inhibitor demonstrated good photothermal properties and photothermal controlled-release properties. The modified CD133 antibodies on the surface of the nano drug carrier helped more drug carriers to enter the PCSCs. The pharmacodynamic effects of the AbCD133@GNR@MSNs@miR-197 inhibitor on PCSCs in vivo and in vitro were studied under near-infrared radiation. The results showed that the AbCD133@GNR@MSNs@miR-197 inhibitor prepared in this study could not only significantly suppress the development of PCSCs through ITGAV/STAT5 pathway but also significantly suppress the growth of PCSC solid tumors. In short, our study verified that miR-197 regulates the development of PCSCs through STAT5 pathway by targeting ITGAV, and the AbCD133@MSNs@GNR@miR-197 inhibitor could be a potential suppressor used in prostate cancer treatment. In short, our study found that miR-197 affected the development of prostate cancer by regulating ITGAV. The AbCD133@GNR@MSNs@miR-197 inhibitor prepared in this study could suppress the development and growth of PCSCs in vitro and in solid tumors not only by targeting the ITGAV but also through photothermal therapy. Our study not only provides a theoretical basis for the clinical treatment of prostate cancer but also provides a research scheme of drug loading and microRNA-based photothermal controlled therapy for prostate cancer.


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