Silodosin inhibits prostate cancer cell growth via ELK1 inactivation and enhances the cytotoxic activity of gemcitabine

Kawahara, Takashi; Aljarah, Ali Kadhim; Shareef, Hasanain Khaleel; Inoue, Satoshi; Ide, Hiroki; Patterson, John M.; Kashiwagi, Eiji; Han, Bin; Li, Yang; Zheng, Yian; Miyamoto, Hiroshi

doi:10.1002/pros.23164

Cited by 21 publications

(21 citation statements)

References 31 publications

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“…Consistent with in vitro and in vivo animal findings in PCa, classical α-antagonists and their analogues appear to have broad activity, exhibiting cytotoxicity in other cancer cell lines including urogenital [44,65,66,67,68,69,70,71,72,73,74], gastrointestinal [73,74,75,76,77], lung [74,78], blood [79], brain [80,81] and thyroid [82]. Importantly, the cytotoxic and anti-proliferative effects are supported by several in vivo mice studies [48,66], suggesting ubiquitous anticancer actions of these drugs.…”

Section: Discussionsupporting

confidence: 58%

The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

Batty

Pugh

Rathinam

et al. 2016

IJMS

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This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects. In vivo data was consistent with in vitro findings as the quinazoline based α-antagonists prevented angiogenesis and decreased tumour mass in mice models of PCa. Mechanistically the cytotoxic and antitumor effects of the α-antagonists appear largely independent of α 1-blockade. The proposed targets include: VEGF, EGFR, HER2/Neu, caspase 8/3, topoisomerase 1 and other mitochondrial apoptotic inducing factors. These cytotoxic effects could not be evaluated in human studies as prospective trial data is lacking. However, retrospective studies show a decreased incidence of PCa in males exposed to α-antagonists. As human data evaluating the use of α-antagonists as treatments are lacking; well designed, prospective clinical trials are needed to conclusively demonstrate the anticancer properties of quinazoline based α-antagonists in PCa and other cancers.

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Section: Discussionsupporting

confidence: 58%

The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

Batty

Pugh

Rathinam

et al. 2016

IJMS

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“…ELK1 regulates various cell processes, including cell proliferation and apoptosis, and can be regulated by miRNAs 42 . ELK1 and pELK-1 expression have been positively associated with several types of cancer, including breast cancer, colonic adenocarcinoma, and prostate cancer 43 – 45 . MiR-150 could regulate ELK1 expression, and ELK1 knockdown could abolish the anti-apoptotic effect of the inhibitor miR-150 in endothelial cells 42 .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-139-3p regulates osteoblast differentiation and apoptosis by targeting ELK1 and interacting with long noncoding RNA ODSM

Wang

et al. 2018

Cell Death Dis

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Recent studies have confirmed that microRNAs and lncRNAs can affect bone cell differentiation and bone formation. In this study, miR-139-3p was upregulated in the femurs of hindlimb unloading mice and MC3T3-E1 cells under simulated microgravity; this effect was related to osteoblast differentiation and apoptosis. Silencing miR-139-3p attenuated the suppression of differentiation and the promotion of MC3T3-E1 cell apoptosis induced by simulated microgravity. ELK1 is a target of miR-139-3p and is essential for miR-139-3p to regulate osteoblast differentiation and apoptosis. An osteoblast differentiation-related lncRNA that could interact with miR-139-3p (lncRNA ODSM) was identified in MC3T3-E1 cells under simulated microgravity. Further investigations demonstrated that lncRNA ODSM could promote MC3T3-E1 cell differentiation. Therefore, this research was the first to reveal the critical role of the lncRNA ODSM/miR-139-3p/ELK1 pathway in osteoblasts, and these findings suggest the potential value of miR-139-3p in osteoporosis diagnosis and therapy.

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“…Studies have demonstrated that Elk1 plays an important role in cancer progression. Kawahara et al found that Elk1 is induced in prostate cancer and promotes tumor development, whereas Elk1 inhibition suppresses tumor growth (44). Additionally, Elk1 is upregulated and promotes cell proliferation in bladder cancer and non-small cell lung cancer (NSCLC) (10).…”

Section: Discussionmentioning

confidence: 99%

Suppression of Elk1 inhibits thyroid cancer progression by mediating PTEN expression

Kong

Yin

et al. 2018

Oncol Rep

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ETS‑domain containing protein (Elk1) is reported to be a member of the ETS oncogene family, and promotes tumorigenesis in cancer such as bladder, prostate and ovarian. Nevertheless, the role of Elk1 in thyroid cancer progression remains unclear. In the present study, we aimed to investigate the role and underlying molecular mechanism of Elk1 in thyroid cancer. The results indicated that Elk1 was significantly upregulated in thyroid cancer tissues and cells. We found that loss of Elk1 function obviously induced the expression of early growth response‑1 (Egr‑1) and PTEN, promoted apoptosis and constrained the proliferation of thyroid cancer cells. Furthermore, Egr‑1 inhibition obviously abrogated the induction of PTEN induced by Elk1 reduction. Moreover, Egr‑1 suppression prevented the promotion of apoptosis and the inhibition of cell proliferation caused by Elk1 reduction. In conclusion, Elk1 inhibition induced thyroid cancer cell apoptosis and restrained their proliferation by regulating Egr‑1/PTEN, indicating a potential role for Elk1 in thyroid cancer treatment.

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Silodosin inhibits prostate cancer cell growth via ELK1 inactivation and enhances the cytotoxic activity of gemcitabine

Cited by 21 publications

References 31 publications

The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

MicroRNA-139-3p regulates osteoblast differentiation and apoptosis by targeting ELK1 and interacting with long noncoding RNA ODSM

Suppression of Elk1 inhibits thyroid cancer progression by mediating PTEN expression

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