Comparative Cytotoxic Activity of Hydroxytyrosol and Its Semisynthetic Lipophilic Derivatives in Prostate Cancer Cells DOI Creative Commons
Antonio J. León‐González, Prudencio Sáez-Martínez, Juan M. Jiménez‐Vacas

et al.

Antioxidants, Journal Year: 2021, Volume and Issue: 10(9), P. 1348 - 1348

Published: Aug. 25, 2021

A high adherence to a Mediterranean diet has been related numerous beneficial effects in human health, including lower incidence and mortality of prostate cancer (PCa). Olive oil is an important source phenolic bioactive compounds, mainly hydroxytyrosol (HT), this diet. Because the growing interest compound its derivatives as chemopreventive agent, we aimed compare vitro effect HT isolated from olive mill wastewaters five semisynthetic alkyl ether, ester, nitro-derivatives against (PCa) cell lines. The proliferation was determined RWPE-1, LNCaP, 22Rv1, PC-3 cells by resazurin assay, migration wound healing tumorsphere colony formation were evaluated. changes key signaling pathways involved carcinogenesis assessed using phosphorylation pathway profiling array Western blotting. Antiproliferative two lipophilic [hydroxytyrosyl acetate (HT-Ac)/ethyl hydroxytyrosyl ether (HT-Et)] significantly higher cancerous 22Rv1 than non-malignant RWPE-1 cells. HT/HT-Ac/HT-Et reduced capacity prostatosphere size whereas only HT-Ac HT-Et these functional parameters PC-3. cytotoxic correlated with modifications pattern proteins, ERK1/2 AKT. Consistently, decreased p-AKT levels In sum, our results suggest that could be considered potential therapeutic tools PCa.

Language: Английский

Current Advances in the Therapeutic Potential of Scutellarin: Novel Applications, Mechanisms, and Future Challenges. DOI Creative Commons
Great Iruoghene Edo, Alice Njolke Mafe, Patrick Othuke Akpoghelie

et al.

Phytomedicine Plus, Journal Year: 2025, Volume and Issue: unknown, P. 100754 - 100754

Published: Jan. 1, 2025

Language: Английский

Citations

2
PTEN‐PI3K pathway alterations in advanced prostate cancer and clinical implications DOI Open Access
Atish D. Choudhury

The Prostate, Journal Year: 2022, Volume and Issue: 82(S1)

Published: June 3, 2022

Abstract Background Despite significant advances in molecular characterization and therapeutic targeting of advanced prostate cancer, it remains the second most common cause cancer death men United States. The PI3K (Phosphatidylinositol 3‐kinase)/AKT (AKT serine/threonine kinase)/mTOR (mammalian target rapamycin) signaling pathway is commonly altered frequently through loss PTEN (Phosphatase Tensin Homolog) tumor suppressor, critical for cell proliferation, migration, survival. Methods This study summarizes PTEN/PI3K pathway, alterations components seen results clinical trials inhibitors reported to date with a focus on more recently studies. It also reviews rationale combination approaches currently under study, including taxanes, immune checkpoint poly (ADP‐ribose) polymerase inhibitors, discusses future directions biomarker testing this pathway. Results Clinical studying pharmacologic PI3K, AKT or mTOR kinases have demonstrated modest activity specific agents, several progress. A key challenge importance PI3K/AKT/mTOR noncancerous tissues, leading predictable but often severe toxicities at doses. Further selective inhibition tumors, development rational combinations, appropriate selection identify tumor‐ patient‐specific vulnerabilities will be required optimize benefit from

Language: Английский

Citations

45
Addressing the Reciprocal Crosstalk between the AR and the PI3K/AKT/mTOR Signaling Pathways for Prostate Cancer Treatment DOI Open Access
Fabio Raith, Daniel H. O’Donovan, Clara Lemos

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2289 - 2289

Published: Jan. 24, 2023

The reduction in androgen synthesis and the blockade of receptor (AR) function by chemical castration AR signaling inhibitors represent main treatment lines for initial stages prostate cancer. Unfortunately, resistance mechanisms ultimately develop due to alterations pathway, such as gene amplification or mutations, also emergence alternative pathways that render tumor less or, more rarely, completely independent activation. An essential oncogenic axis activated cancer is phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target rapamycin (mTOR) evidenced frequent negative regulator phosphatase tensin homolog (PTEN) activating mutations PI3K subunits. Additionally, crosstalk reciprocal feedback loops between PI3K/AKT/mTOR cascade activate pro-survival signals play an role disease recurrence progression have been evidenced. Inhibitors addressing different players pathway evaluated clinic. Only a limited benefit has reported up now associated side effects, so novel combination approaches biomarkers predictive patient response are urgently needed. Here, we reviewed recent data on selective identified, most advanced clinical studies, with focus treatments. A deeper understanding complex molecular involved further guide therapeutic improved outcomes.

Language: Английский

Citations

26
Molecular Mechanisms of Prostate Cancer Development in the Precision Medicine Era: A Comprehensive Review DOI Open Access
Shigekatsu Maekawa, Ryo Takata,

Wataru Obara

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 523 - 523

Published: Jan. 25, 2024

The progression of prostate cancer (PCa) relies on the activation androgen receptor (AR) by androgens. Despite efforts to block this pathway through deprivation therapy, resistance can occur several mechanisms, including abnormal AR, resulting in castration-resistant PCa following introduction treatment. Mutations, amplifications, and splicing variants AR-related genes have garnered attention regard. Furthermore, recent large-scale next-generation sequencing analysis has revealed critical roles AR genes, as well DNA repair, PI3K, cell cycle pathways, onset PCa. Moreover, research epigenomics microRNA increasingly become popular; however, it not translated into development effective therapeutic strategies. Additionally, treatments targeting homologous recombination repair mutations PI3K/Akt been developed are accessible, multiple clinical trials investigated efficacy immune checkpoint inhibitors. In comprehensive review, we outline status genomics briefly explore potential future developments field epigenetic modifications microRNAs.

Language: Английский

Citations

11
PTEN suppresses renal cell carcinoma proliferation and migration via inhibition of the PI3K/AKT pathway DOI Creative Commons

Xu Xu,

Ya‐ling Tang,

Xiaohong Liang

et al.

World Journal of Surgical Oncology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 5, 2025

Renal cell carcinoma (RCC) is a frequent and aggressive type of kidney cancer with limited therapeutic options. Although phosphatase tensin homolog (PTEN) have been recognized as potential tumor suppressor in all kinds cancers, its function RCC remains to be thoroughly elucidated. This article was recruited examine the PTEN's role managing PI3K/AKT pathway impact on proliferation migration. study collected renal adjacent non-cancerous tissue samples from our hospital. HK-2 786-O cells were used, divided into control, vector, oe-PTEN groups. PTEN related protein levels detected using RT-qPCR Western blot. Statistical analyses performed Mann-Whitney U test Kruskal-Wallis H test. Cell viability migration assessed CCK-8 assay wound healing assay. All conducted SPSS 22.0 software, statistical significance defined p < 0.05. results showed that expression significantly increased tissues compared normal (p 0.01). However, mRNA reduced In low expression, further induction overexpression inhibited signaling activity 0.01), accompanied by decreased ability. These indicate pattern complex, but can exert tumor-suppressive effects inhibiting pathway. Our findings demonstrate leads signaling, decreasing highlights critical progression suggests targets for intervention.

Language: Английский

Citations

1
Disassembly of α6β4-mediated hemidesmosomal adhesions promotes tumorigenesis in PTEN-negative prostate cancer by targeting plectin to focal adhesions DOI Creative Commons
Tomasz Wenta, Anette Schmidt, Qin Zhang

et al.

Oncogene, Journal Year: 2022, Volume and Issue: 41(30), P. 3804 - 3820

Published: July 1, 2022

Loss of α6β4-dependent hemidesmosomal adhesions has been observed during prostate cancer progression. However, the significance and underlying mechanisms by which aberrant hemidesmosome assembly may modulate tumorigenesis remain elusive. Using an extensive CRISPR/Cas9-mediated genetic engineering approaches in different cell lines combined with vivo studies mice, bone marrow-on-chip assays bioinformatics, as well histological analysis patient cohorts, we demonstrated that simultaneous loss PTEN induced several tumorigenic properties including proliferation, migration, resistance to anoikis, apoptosis, drug treatment vitro, increased metastatic capacity vivo. These effects were plectin-depended plectin was associated actin-rich upon disruption PTEN-negative cells leading activation EGFR/PI3K/Akt- FAK/Src-pathways. results suggest proteins have diagnostic value helping stratify patients high risk for development aggressive disease highlight actin-associated a potential therapeutic target specifically PTEN/hemidesmosome dual-negative cancer.

Language: Английский

Citations

31
Deregulated microRNAs Involved in Prostate Cancer Aggressiveness and Treatment Resistance Mechanisms DOI Open Access

Himali Gujrati,

Siyoung Ha,

Bi‐Dar Wang

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(12), P. 3140 - 3140

Published: June 10, 2023

Prostate cancer (PCa) is the most frequently diagnosed and second leading cause of deaths among American men. Complex genetic epigenetic mechanisms are involved in development progression PCa. MicroRNAs (miRNAs) short noncoding RNAs that regulate protein expression at post-transcriptional level by targeting mRNAs for degradation or inhibiting translation. In past two decades, field miRNA research has rapidly expanded, emerging evidence revealed dysfunction to be an important mechanism underlying a wide range diseases, including cancers. This review article focuses on understanding functional roles molecular deregulated miRNAs PCa aggressiveness drug resistance based existing literature. Specifically, differentially expressed (upregulated downregulated) vs. normal tissues, advanced low-grade PCa, treatment-responsive non-responsive discussed. particular, oncogenic tumor-suppressive regulation (1) synthesis androgen receptor (AR) its AR-V7 splice variant, (2) PTEN PTEN-mediated signaling, (3) RNA splicing mechanisms, (4) chemo- hormone-therapy resistance, (5) racial disparities discussed summarized. We further provide overview current advances challenges miRNA-based biomarkers therapeutics clinical practice diagnosis/prognosis treatment.

Language: Английский

Citations

20
Therapeutic importance and diagnostic function of circRNAs in urological cancers: from metastasis to drug resistance DOI
Zhibin Zhang,

Z.M. Guo K.L. Gao,

Huimin Fang

et al.

Cancer and Metastasis Reviews, Journal Year: 2024, Volume and Issue: 43(3), P. 867 - 888

Published: Jan. 22, 2024

Language: Английский

Citations

8
Targeting IL-8 and Its Receptors in Prostate Cancer: Inflammation, Stress Response, and Treatment Resistance DOI Open Access

Shauna McClelland,

Pamela Maxwell,

Cristina Branco

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(16), P. 2797 - 2797

Published: Aug. 8, 2024

This review delves into the intricate roles of interleukin-8 (IL-8) and its receptors, CXCR1 CXCR2, in prostate cancer (PCa), particularly castration-resistant (CRPC) metastatic CRPC (mCRPC). emphasizes crucial role tumour microenvironment (TME) inflammatory cytokines promoting progression response to cell targeting agents. IL-8, acting through C-X-C chemokine receptor type 1 (CXCR1) 2 (CXCR2), modulates multiple signalling pathways, enhancing angiogenesis, proliferation, migration cells. highlights shift PCa research focus from solely cells non-cancer-cell components, including vascular endothelial cells, extracellular matrix, immune dynamic interactions within TME. The immunosuppressive nature TME significantly influences resistance emerging therapies. Current treatment modalities, androgen deprivation therapy chemotherapeutics, encounter persistent are complicated by cancer’s notably “immune-cold” nature, which limits system tumour. These challenges underscore critical need for novel approaches that both overcome enhance engagement therapeutic potential inhibiting IL-8 is explored, with studies showing enhanced sensitivity treatments, radiation inhibitors. Clinical trials, such as ACE trial, demonstrate efficacy combining CXCR2 inhibitors existing offering significant benefits, especially patients resistant PCa. also addresses chemokines, noting complexity precision avoid side effects optimize outcomes.

Language: Английский

Citations

5
The Effect of Metformin on Male Reproductive Function and Prostate: An Updated Review DOI Creative Commons
Chin‐Hsiao Tseng

The World Journal of Men s Health, Journal Year: 2021, Volume and Issue: 40(1), P. 11 - 11

Published: March 16, 2021

Metformin is the first-line oral antidiabetic drug that shows multiple pleiotropic effects of anti-inflamation, anti-cancer, anti-aging, anti-microbia, anti-atherosclerosis, and immune modulation. Metformin's on men's related health are reviewed here, focusing reproductive under subtitles erectile dysfunction (ED), steroidogenesis spermatogenesis; prostate-related prostate specific antigen (PSA), prostatitis, benign hyperplasia (BPH), cancer (PCa). Updated literature suggests a potential role metformin arteriogenic ED but controversial contradictory (either protective or harmful) testicular functions testosterone synthesis spermatogenesis. With regards to health, use may be associated with lower levels PSA in humans, its clinical implications require more research. Although there lack research metform's effect it have benefits through anti-microbial anti-inflammatory properties. reduce risk BPH by inhibiting insulin-like growth factor 1 pathway some not all studies suggest PCa. Many trials being conducted investigate as an adjuvant therapy for PCa results currently available conclusive. While benefit reducing metastasis recurrence PCa, others do show any benefit. More works warranted illuminate usefulness promotion health.

Language: Английский

Citations

29