Novel bone microenvironment model of castration‑resistant prostate cancer with chitosan fiber matrix and osteoblasts

Samoto, Masahiro; Matsuyama, Hideyasu; Matsumoto, Hiroaki; Hirata, Hiroshi; Ueno, Koji; Ozawa, Sho; Mori, Junichi; Inoue, Ryo; Yano, Seiji; Yamamoto, Yoshiaki; Haginaka, Jun; Horiyama, Shizuyo; Tamada, Koji

doi:10.3892/ol.2021.12950

Cited by 4 publications

(5 citation statements)

References 38 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The observation and analysis of the spheroid area were performed and quantified using Cell 3 iMager duos (SCREEN Holdings Co., Ltd.) and ImageJ software, respectively. 29 The fold increase of the spheroid area was determined by the ratio between the spheroid area of each day and the spheroid area at day 0.…”

Section: Methodsmentioning

confidence: 99%

Physicochemical and Biopharmaceutical Controllability of New Self-Assembled Fatty Acid Conjugated Leuprolide for the Enhanced Anticancer Activity

Ngo¹,

Bak²,

Nguyen³

et al. 2023

IJN

View full text Add to dashboard Cite

Background Leuprolide (LEU), a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH), could exert a direct inhibitory activity on the proliferation of prostate cancer cells. However, the short half-life in blood and the biopharmaceutical problem of LEU limit this anticancer activity. Purpose To improve its druggability for improving anticancer activity, the amine-group targeted LEU was conjugated with different chain lengths of saturated fatty acids (FAs). Methods LEU–fatty acid conjugates (LFCs) were synthesized by exploiting N-hydroxysuccinimidyl (NHS) conjugation chemistry. The physicochemical properties and the self-assembled behaviors of the conjugates were extensively investigated. The in vitro anticancer activity of three LFCs was extensively studied in both 2D monolayer and 3D spheroid culture models of a prostate cancer cell line, PC3. Results Three LFCs could be readily self-assembled into nanoparticles (LFNs) with a small size of around 100 nm, positive charges, and exhibited greater permeability rates compared to the same concentration of LEU, excluding LSN. The chain length of FA in conjugate was positively related to the selectivity index between cancer cells and non-cancerous cell lines. All LFCs showed a superior direct antiproliferative effect on cancer cells in the following order: LSC (98.9%) > LPC (86.7%) > LLC (75.0%) > LEU (8.9%) after repeat daily of the same dose strength of LEU for 4 days. In addition, the 3D spheroid model study indicates that all LFCs with a one-time treatment performed a long-acting inhibitory effect on tumor growth as compared to LEU after 7 days. Conclusion The conjugation of LEU with different chain lengths of FAs could provide a novel strategy to improve peptide stability and exert an additional superior direct inhibitory effect for the treatment of several hormone-responsive tumor systems using therapeutic peptides.

show abstract

Section: Methodsmentioning

confidence: 99%

Physicochemical and Biopharmaceutical Controllability of New Self-Assembled Fatty Acid Conjugated Leuprolide for the Enhanced Anticancer Activity

Ngo¹,

Bak²,

Nguyen³

et al. 2023

IJN

View full text Add to dashboard Cite

show abstract

“…Furthermore, it has been suggested that adding dutasteride to endocrine therapy might have a more potent inhibitory effect on AR signaling in prostate cancer. Indeed, we and others have reported that a combination of abiraterone and dutasteride decreased intratumoral testosterone and DHT concentrations and showed excellent synergistic anticancer effects in CRPC C4‐2 cells 15,16 . In addition, Li et al reported that abiraterone was metabolized into Δ4‐abiraterone (D4A) by 3β‐hydroxysteroid dehydrogenase, and then further metabolized by 5α‐reductase into 3‐keto‐5α‐abiraterone, which is agonistic to AR and promotes prostate cancer progression 16,17 .…”

mentioning

confidence: 93%

“…Indeed, we and others have reported that a combination of abiraterone and dutasteride decreased intratumoral testosterone and DHT concentrations and showed excellent synergistic anticancer effects in CRPC C4-2 cells. 15,16 In addition, Li et al reported that abiraterone was metabolized into 4-abiraterone (D4A) by 3β-hydroxysteroid dehydrogenase, and then further metabolized by 5α-reductase into 3-keto-5αabiraterone, which is agonistic to AR and promotes prostate cancer progression. 16,17 Then, it is hypothesized that D4A concentration is increased by blocking 5α-reductase.…”

mentioning

confidence: 99%

“…15,16 In addition, Li et al reported that abiraterone was metabolized into 4-abiraterone (D4A) by 3β-hydroxysteroid dehydrogenase, and then further metabolized by 5α-reductase into 3-keto-5αabiraterone, which is agonistic to AR and promotes prostate cancer progression. 16,17 Then, it is hypothesized that D4A concentration is increased by blocking 5α-reductase.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A Phase II Trial of Abiraterone With Dutasteride for Second‐Generation Antiandrogen‐ and Chemotherapy‐Naïve Patients With Castration‐Resistant Prostate Cancer

Shiota

Inoue

Tashiro

et al. 2023

The Journal of Clinical Pharma

Self Cite

View full text Add to dashboard Cite

The development of a novel therapy to overcome primary and acquired resistance to abiraterone is an unmet need. This study aimed to evaluate the efficacy and safety of adding 5α-reductase inhibitor dutasteride to abiraterone, explore proof of concept, and identify candidates suitable for combination therapy. This phase II, single-arm, and open-label study enrolled second-generation antiandrogen-and chemotherapy-naïve patients with castration-resistant prostate cancer. Patients received abiraterone and prednisolone for 4 weeks, followed by adding dutasteride. The primary end point was a 50% prostate-specific antigen response rate. Serum concentrations of abiraterone and its metabolites as well as HSD3B1 and SRD5A2 genotypes were measured. The association between drug metabolism and genotypes and their impact on the efficacy of combination therapy were assessed. Among 21 patients, 18 (85.7%) achieved ≥50% PSA reduction. Median time to treatment failure was not reached during the median followup of 15.4 months. No patients experienced grade ≥3 adverse events. Although dutasteride reduced serum 3-keto-5α-abiraterone concentrations, higher serum 3-keto-5α-abiraterone concentrations on combination therapy were associated with a shorter time to treatment failure. HSD3B1 and SRD5A2 genotypes were associated with serum 4-abiraterone and 3-keto-5α-abiraterone concentrations before adding dutasteride, respectively. Time to treatment failure was longer in patients with homozygous wild-type HSD3B1, but comparable between those with the SRD5A2 genotype. The promising outcomes of this study warrant further investigation of combination therapy in a randomized trial. Stratification by HSD3B1 and SRD5A2 genetic profiles might identify patients suitable for combination therapy.

show abstract

“…Beyond question, communication between bone and PCa cells is crucial in promoting the development of bone metastases . So far, few studies investigated this key aspect in 3D settings. − …”

Section: Introductionmentioning

confidence: 99%

TempEasy 3D Hydrogel Coculture System Provides Mechanistic Insights into Prostate Cancer Bone Metastasis

Zhang,

Chen,

Sun

et al. 2024

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

Patients diagnosed with advanced prostate cancer (PCa) often experience incurable bone metastases; however, a lack of relevant experimental models has hampered the study of disease mechanisms and the development of therapeutic strategies. In this study, we employed the recently established Temperature-based Easy-separable (TempEasy) 3D cell coculture system to investigate PCa bone metastasis. Through coculturing PCa and bone cells for 7 days, our results showed a reduction in PCa cell proliferation, an increase in neovascularization, and an enhanced metastasis potential when cocultured with bone cells. Additionally, we observed increased cell proliferation, higher stemness, and decreased bone matrix protein expression in bone cells when cocultured with PCa cells. Furthermore, we demonstrated that the stiffness of the extracellular matrix had a negligible impact on molecular responses in both primary (PCa cells) and distant malignant (bone cells) sites. The TempEasy 3D hydrogel coculture system is an easy-to-use and versatile coculture system that provides valuable insights into the mechanisms of cell–cell communication and interaction in cancer metastasis.

show abstract

Novel bone microenvironment model of castration‑resistant prostate cancer with chitosan fiber matrix and osteoblasts

Cited by 4 publications

References 38 publications

Physicochemical and Biopharmaceutical Controllability of New Self-Assembled Fatty Acid Conjugated Leuprolide for the Enhanced Anticancer Activity

Physicochemical and Biopharmaceutical Controllability of New Self-Assembled Fatty Acid Conjugated Leuprolide for the Enhanced Anticancer Activity

A Phase II Trial of Abiraterone With Dutasteride for Second‐Generation Antiandrogen‐ and Chemotherapy‐Naïve Patients With Castration‐Resistant Prostate Cancer

TempEasy 3D Hydrogel Coculture System Provides Mechanistic Insights into Prostate Cancer Bone Metastasis

Contact Info

Product

Resources

About