Sabutoclax, a Mcl-1 Antagonist, Inhibits Tumorigenesis in Transgenic Mouse and Human Xenograft Models of Prostate Cancer

ABSTRACT Prostate cancer (PCa) is one of the important factors of cancer deaths especially in the western countries. Hispidulin (4′,5,7-trihydroxy-6-methoxyflavone) is a phenolic flavonoid compound proved to possess anticancer properties, but its effects on PCa are left to be released. The aims of this study were to investigate the effects and the relative mechanisms of Hispidulin on PCa development. Hispidulin administration inhibited proliferation, invasion, and migration, while accelerated apoptosis in Du145 and VCaP cells, which was accompanied by PPARγ activation and autophagy enhancement. The beneficial effects of Hispidulin could be diminished by PPARγ inhibition. Besides, Hispidulin administration suppressed PCa tumorigenicity in Xenograft models, indicating the anticancer properties in vivo. Therefore, our work revealed that the anticancer properties of Hispidulin might be conferred by its activation on PPARγ and autophagy.

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Characterization of tumor‐associated macrophages in prostate cancer transgenic mouse models

The Prostate ◽

10.1002/pros.24139 ◽

2021 ◽

Author(s):

Amber E. Groot ◽

Kayla V. Myers ◽

Timothy E. G. Krueger ◽

Ashley L. Kiemen ◽

Natalia H. Nagy ◽

...

Keyword(s):

Prostate Cancer ◽

Transgenic Mouse ◽

Mouse Models ◽

Transgenic Mouse Models ◽

Tumor Associated Macrophages

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Dandelion Root and Lemongrass Extracts Induce Apoptosis, Enhance Chemotherapeutic Efficacy, and Reduce Tumour Xenograft Growth In Vivo in Prostate Cancer

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/2951428 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Christopher Nguyen ◽

Ali Mehaidli ◽

Kiruthika Baskaran ◽

Sahibjot Grewal ◽

Alaina Pupulin ◽

...

Keyword(s):

Prostate Cancer ◽

Root Extract ◽

Natural Health Products ◽

Anticancer Efficacy ◽

Adjuvant Therapies ◽

Anticancer Effects ◽

Health Products ◽

Xenograft Models ◽

Pharmaceutical Uses

Many conventional chemotherapies have indicated side effects due to a lack of treatment specificity and are thus not suitable for long-term usage. Natural health products are well-tolerated and safe for consumption, and some have pharmaceutical uses particularly for their anticancer effects. We have previously reported the anticancer efficacy of dandelion (Taraxacum officinale) root and lemongrass (Cymbopogon citratus) extracts. However, their efficacy on prostate cancer and their interactions with standard chemotherapeutics have not been studied to determine if they will be suitable for adjuvant therapies. If successful, these extracts could potentially be used in conjunction with chemotherapeutics to minimize the risk of drug-related toxicity and enhance the efficacy of the treatment. We have demonstrated that both dandelion root extract (DRE) and lemongrass extract (LGE) exhibit selective anticancer activity. Importantly, DRE and LGE addition to the chemotherapeutics taxol and mitoxantrone was determined to enhance the induction of apoptosis when compared to individual chemotherapy treatment alone. Further, DRE and LGE were able to significantly reduce the tumour burden in prostate cancer xenograft models when administered orally, while also being well-tolerated. Thus, the implementation of these well-tolerated extracts in adjuvant therapies could be a selective and efficacious approach to prostate cancer treatment.

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The intriguing role of fibroblasts and c-Jun in the chemo-preventive and therapeutic effect of finasteride on xenograft models of prostate cancer

Asian Journal of Andrology ◽

10.4103/1008-682x.167714 ◽

2015 ◽

Vol 0 (0) ◽

pp. 0

Author(s):

Yi-Nong Niu ◽

Kai Wang ◽

Song Jin ◽

Dong-Dong Fan ◽

Ming-Shuai Wang ◽

...

Keyword(s):

Prostate Cancer ◽

Therapeutic Effect ◽

Xenograft Models

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A Transgenic Mouse Prostate Cancer Model

Toxicologic Pathology ◽

10.1177/019262339602400414 ◽

1996 ◽

Vol 24 (4) ◽

pp. 502-504 ◽

Cited By ~ 76

Author(s):

J.R. Gingrich ◽

N.M. Greenberg

Keyword(s):

Prostate Cancer ◽

Transgenic Mouse ◽

Cancer Model ◽

Mouse Prostate ◽

Prostate Cancer Model

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68Ga-labeled ODAP-Urea-based PSMA Agents in Prostate Cancer: First-in-human Imaging of an Optimized Agent

10.21203/rs.3.rs-364739/v1 ◽

2021 ◽

Author(s):

Xiaojiang Duan ◽

Zhen Cao ◽

Hua Zhu ◽

Chen Liu ◽

Xiaojun Zhang ◽

...

Keyword(s):

Prostate Cancer ◽

Human Study ◽

Radiochemical Yield ◽

Cell Uptake ◽

Normal Organ ◽

Promising Target ◽

Pharmacokinetic Properties ◽

Xenograft Models ◽

Specific Membrane ◽

Yield And Purity

Abstract Purpose: Prostate-specific membrane antigen (PSMA) is a promising target for prostate cancer imaging and therapy. The most commonly used scaffold incorporates a glutamate-urea (Glu-Urea) function. We recently developed oxalyldiaminopropionic acid-urea (ODAP-Urea) PSMA ligands in an attempt to improve upon the pharmacokinetic properties of existing agents. Here we report the synthesis of an optimized 68 Ga-labeled ODAP-Urea-based ligand, [ 68 Ga]Ga-P 137 , and first-in-human results. Methods: Twelve ODAP-Urea-based ligands were synthesized and radiolabeled with 68 Ga in high radiochemical yield and purity. Their PSMA inhibitory capacities were determined using the NAALADase assay. Radioligands were evaluated in mice bearing 22Rv1 prostate tumors by microPET. Lead compound [ 68 Ga]Ga-P 137 was evaluated for stability, cell uptake and biodistribution. PET imaging of [ 68 Ga]Ga-P 137 was performed in three patients head-to-head compared to [ 68 Ga]Ga-PSMA-617. Results : Ligands were synthesized in 11.1%-44.4% yield and >95% purity. They have high affinity to PSMA( K i of 0.13 NM to 5.47 nM). [ 68 Ga]Ga-P 137 was stable and hydrophilic. [ 68 Ga]Ga-P 137 showed higher uptake than [ 68 Ga]Ga-PSMA-617 in tumor-bearing mice at 6.43 ± 0.98 %ID/g vs 3.41 ± 1.31 %ID/g at 60 min post-injection. In humans studies, the normal organ biodistribution of [ 68 Ga]Ga-P 137 was grossly equivalent to that of [ 68 Ga]Ga-PSMA-617 except for within the urinary tract, in which [ 68 Ga]Ga-P 137 demonstrated lower uptake. Conclusion: The optimized ODAP-Urea-based ligand [ 68 Ga]Ga-P 137 can image PSMA in xenograft models and humans, with lower bladder accumulation to the Glu-Urea-based agent, [ 68 Ga]Ga-PSMA-617, in a preliminary, first-in-human study.

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Prostate cancer xenograft models

Prostate and Renal Cancer, Benign Prostatic Hyperplasia, Erectile Dysfunction and Basic Research ◽

10.3109/9780203010778-24 ◽

2003 ◽

pp. 236-245

Keyword(s):

Prostate Cancer ◽

Xenograft Models

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Small-molecule inhibitor targeting orphan nuclear receptor COUP-TFII for prostate cancer treatment

Science Advances ◽

10.1126/sciadv.aaz8031 ◽

2020 ◽

Vol 6 (18) ◽

pp. eaaz8031 ◽

Cited By ~ 1

Author(s):

Leiming Wang ◽

Chiang-Min Cheng ◽

Jun Qin ◽

Mafei Xu ◽

Chung-Yang Kao ◽

...

Keyword(s):

Prostate Cancer ◽

Nuclear Receptor ◽

High Throughput Screening ◽

Target Gene ◽

Target Genes ◽

Orphan Nuclear Receptor ◽

Prostate Cancer Treatment ◽

Molecule Inhibitor ◽

Transcription Regulators ◽

Xenograft Models

The orphan nuclear receptor COUP-TFII is expressed at a low level in adult tissues, but its expression is increased and shown to promote progression of multiple diseases, including prostate cancer, heart failure, and muscular dystrophy. Suppression of COUP-TFII slows disease progression, making it an intriguing therapeutic target. Here, we identified a potent and specific COUP-TFII inhibitor through high-throughput screening. The inhibitor specifically suppressed COUP-TFII activity to regulate its target genes. Mechanistically, the inhibitor directly bound to the COUP-TFII ligand-binding domain and disrupted COUP-TFII interaction with transcription regulators, including FOXA1, thus repressing COUP-TFII activity on target gene regulation. Through blocking COUP-TFII’s oncogenic activity in prostate cancer, the inhibitor efficiently exerted a potent antitumor effect in xenograft mouse models and patient-derived xenograft models. Our study identified a potent and specific COUP-TFII inhibitor that may be useful for the treatment of prostate cancer and possibly other diseases.

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