دورية أكاديمية
Oleocanthal Attenuates Metastatic Castration-Resistant Prostate Cancer Progression and Recurrence by Targeting SMYD2
| العنوان: | Oleocanthal Attenuates Metastatic Castration-Resistant Prostate Cancer Progression and Recurrence by Targeting SMYD2 |
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| المؤلفون: | Abu Bakar Siddique, Hassan Y. Ebrahim, Afsana Tajmim, Judy Ann King, Khaldoun S. Abdelwahed, Zakaria Y. Abd Elmageed, Khalid A. El Sayed |
| المصدر: | Cancers, Vol 14, Iss 14, p 3542 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | castration-resistant, prostate cancer, extra-virgin olive oil, nutraceutical, oleocanthal, progression, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Metastatic castration-resistant prostate cancer (mCRPC) is the most aggressive prostate cancer (PC) phenotype. Cellular lysine methylation is driven by protein lysine methyltransferases (PKMTs), such as those in the SET- and MYND-containing protein (SMYD) family, including SMYD2 methylate, and several histone and non-histone proteins. SMYD2 is dysregulated in metastatic PC patients with high Gleason score and shorter survival. The Mediterranean, extra-virgin-olive-oil-rich diet ingredient S-(-)-oleocanthal (OC) inhibited SMYD2 in biochemical assays and suppressed viability, migration, invasion, and colony formation of PC-3, CWR-R1ca, PC-3M, and DU-145 PC cell lines with IC50 range from high nM to low µM. OC’s in vitro antiproliferative effect was comparable to standard anti-PC chemotherapies or hormone therapies. A daily, oral 10 mg/kg dose of OC for 11 days effectively suppressed the progression of the mCRPC CWR-R1ca cells engrafted into male nude mice. Daily, oral OC treatment for 30 days suppressed tumor locoregional and distant recurrences after the primary tumors’ surgical excision. Collected OC-treated animal tumors showed marked SMYD2 reduction. OC-treated mice showed significant serum PSA reduction. For the first time, this study showed SMYD2 as novel molecular target in mCRPC, and OC emerged as a specific SMYD2 lead inhibitor. OC prevailed over previously reported SMYD2 inhibitors, with validated in vivo potency and high safety profile, and, therefore, is proposed as a novel nutraceutical for mCRPC progression and recurrence control. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 14143542 2072-6694 |
| Relation: | https://www.mdpi.com/2072-6694/14/14/3542; https://doaj.org/toc/2072-6694 |
| DOI: | 10.3390/cancers14143542 |
| URL الوصول: | https://doaj.org/article/7c22a2c8df9443f5a6f718891975514b |
| رقم الأكسشن: | edsdoj.7c22a2c8df9443f5a6f718891975514b |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14143542 20726694 |
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| DOI: | 10.3390/cancers14143542 |