Last update 01 Nov 2024

STAT x AR x PARP

Last update 01 Nov 2024

Basic Info

Related Targets

STATARPARP

Drugs associated with STAT x AR x PARP

XNTR-936

Target

AR x PARP x STAT

Mechanism

AR antagonists [+2]

Active Org.

Xennials Therapeutics, Inc.

Originator Org.

Xennials Therapeutics, Inc.

Active Indication

Neoplasms [+2]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with STAT x AR x PARP

100 Translational Medicine associated with STAT x AR x PARP

0 Patents (Medical) associated with STAT x AR x PARP

Literatures (Medical) associated with STAT x AR x PARP

01 Feb 2024·Phytotherapy Research

The microRNA‐193a‐5p induced ROS production and disturbed colocalization between STAT3 and androgen receptor play critical roles in cornin induced apoptosis

Article

Author: Choi, Jhin-Baek ; Khil, Jae-Ho ; Shim, Bum-Sang ; Sim, Deok Yong ; Park, Ji Eon ; Park, Su-Yeon ; Ko, Hwan-Joo ; Lee, Hyo-Jung ; Kim, Bonglee ; Ahn, Chi-Hoon ; Kim, Sung-Hoon

AbstractThough cornin is known to induce angiogenic, cardioprotective, and apoptotic effects, the apoptotic mechanism of this iridoid monoglucoside is not fully understood in prostate cancer cells to date. To elucidate the antitumor mechanism of cornin, cytotoxicity assay, cell cycle analysis, Western blotting, RT‐qPCR, RNA interference, immunofluorescence, immunoprecipitation, reactive oxygen species (ROS) measurement, and inhibitor assay were applied in this work. Cornin exerted cytotoxicity, increased sub‐G1 population, and cleaved PARP and caspase3 in LNCaP cells more than in DU145 cells. Consistently, cornin suppressed phosphorylation of signal transducer and activator of transcription 3 (STAT3) and disrupted the colocalization of STAT3 and androgen receptor (AR) in LNCaP and DU145 cells, along with suppression of AR, prostate‐specific antigen (PSA), and 5α‐reductase in LNCaP cells. Furthermore, cornin increased ROS production and the level of miR‐193a‐5p, while ROS inhibitor N‐acetylcysteine disturbed the ability of cornin to attenuate the expression of AR, p‐STAT3, PSA, pro‐PARP, and pro‐caspase3 in LNCaP cells. Notably, miR‐193a‐5p mimics the enhanced apoptotic effect of cornin, while miR‐193a‐5p inhibitor reverses the ability of cornin to abrogate AR, PSA, and STAT3 in LNCaP cells. Our findings suggest that ROS production and the disturbed crosstalk between STAT3 and AR by microRNA‐193a‐5p are critically involved in the apoptotic effect of cornin in prostate cancer cells.

01 Oct 2018·Journal of Cellular PhysiologyQ2 · BIOLOGY

Interleukin‐6 induced overexpression of valosin‐containing protein (VCP)/p97 is associated with androgen‐independent prostate cancer (AIPC) progression

Q2 · BIOLOGY

Article

Author: Reddy Kami Reddy, Karthik ; Ummanni, Ramesh ; Dasari, Chandrashekhar ; Bhukya, Supriya ; Duscharla, Divya

Though Androgen deprivation therapy (ADT) is effective initially, numerous patients become resistant to it and develop castration resistant PCa (CRPC). Cytokines promotes ligand independent activation of AR. Interleukin‐6 (IL‐6) levels are elevated in CRPC patients and regulate AR activity. However, progression to CRPC is not fully understood. In this study, we analyzed differential protein expression in LNCaP cells treated with IL‐6 using proteomics. Results revealed altered expression of 27 proteins and Valosin‐containing protein (VCP)/p97 plays a predominant role in co‐regulation of altered proteins. Interestingly, IL‐6 induced VCP expression through Pim‐1 via STAT3 is AR independent there by suggesting a role for VCP in CRPC. Transfection of LNCaP cells for VCP overexpression showed an increased cell proliferation, migration, and invasion where as its inhibition by NMS‐873 showed the reverse effect causing cell death. Mechanistic studies demonstrate that cell death occurs due to apoptosis by endoplasmic reticulum (ER) stress, elevated cell cycle inhibitors p21, p27kip1, and active PARP and reduced Bcl‐2. VCP promotes cell invasion and migration by altering E‐cadherin and Vimentin levels inversely triggering EMT of PCa cells. VCP immunostaining revealed no staining in BPH but strong staining in PCa. This study determines VCP may play an important role in progression to CRPC and it can be a favorable target with to develop new therapies to treat ADT resistant prostate cancer.

18 Aug 2017·Nutrition and CancerQ4 · MEDICINE

Hydroxytyrosol Induces Apoptosis and Cell Cycle Arrest and Suppresses Multiple Oncogenic Signaling Pathways in Prostate Cancer Cells

Q4 · MEDICINE

Article

Author: Khan, Mohammad Aslam ; Singh, Ajay Partap ; Zubair, Haseeb ; Ahmad, Aamir ; Bhardwaj, Arun ; Patel, Girijesh Kumar ; Singh, Seema ; Srivastava, Sanjeev Kumar

SCOPEHydroxytyrosol (HT), a polyphenol from olives, is a potential anticancer agent. This study was designed to evaluate the anticancer activity of HT against prostate cancer cells, and the mechanism thereof.METHODS AND RESULTSTreatment of LNCaP and C4-2 prostate cancer cells with HT resulted in a dose-dependent inhibition of proliferation. This was in contrast to HT's ineffectiveness against normal prostate epithelial cells RWPE1 and PWLE2, suggesting cancer-cell-specific effect. HT induced G1/S cell cycle arrest, with inhibition of cyclins D1/E and cdk2/4 and induction of inhibitory p21/p27. HT also induced apoptosis, as confirmed by flow cytometry, caspase activation, PARP cleavage, and BAX/Bcl-2 ratio. It inhibited the phosphorylation of Akt/STAT3, and induced cytoplasmic retention of NF-κB, which may explain its observed effects. Finally, HT inhibited androgen receptor (AR) expression and the secretion of AR-responsive prostate-specific antigen.CONCLUSIONCastration-resistant prostate cancers retain AR signaling and are often marked by activated Akt, NF-κB, and STAT3 signaling. Our results establish a pleiotropic activity of HT against these oncogenic signaling pathways. Combined with its nontoxic effects against normal cells, our results support further testing of HT for prostate cancer therapy.

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