دورية أكاديمية
Overcoming Resistance in Prostate Cancer Therapy Using a DZ-Simvastatin Conjugate
| العنوان: | Overcoming Resistance in Prostate Cancer Therapy Using a DZ-Simvastatin Conjugate |
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| المؤلفون: | Yan Ou, Gina Chia-Yi Chu, Ji Lyu, Liyuan Yin, Adrian Lim, Ning Zhai, Xiaojiang Cui, Michael S. Lewis, Mouad Edderkaoui, Stephen J. Pandol, Ruoxiang Wang, Yi Zhang |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | Biophysics, Biochemistry, Medicine, Cell Biology, Genetics, Molecular Biology, Pharmacology, Biotechnology, Cancer, Hematology, Plant Biology, Chemical Sciences not elsewhere classified, traditional systemic treatments, significant side effects, research evaluated simvastatin, documented safety profile, demonstrated chemopreventive effects, delivery method using, androgen receptor status, inherent therapeutic resistance, circumvent therapeutic resistance, pc cell lines, pc ), particularly, including hormonal therapy, cell targeting specificity, conjugate formed adducts, xenograft tumor models, promoting cell death, tumor cell targeting |
| الوصف: | Prostate cancer (PC), particularly its metastatic castration-resistant form (mCRPC), is a leading cause of cancer-related deaths among men in the Western world. Traditional systemic treatments, including hormonal therapy and chemotherapy, offer limited effectiveness due to tumors’ inherent resistance to these therapies. Moreover, they often come with significant side effects. We have developed a delivery method using a tumor-cell-specific heptamethine carbocyanine dye (DZ) designed to transport therapeutic agents directly to tumor cells. This research evaluated simvastatin (SIM) as the antitumor payload because of its demonstrated chemopreventive effects on human cancers and its well-documented safety profile. We designed and synthesized a DZ-SIM conjugate for tumor cell targeting. PC cell lines and xenograft tumor models were used to assess tumor-cell targeting specificity and killing activity and to investigate the corresponding mechanisms. DZ-SIM treatment effectively killed PC cells regardless of their androgen receptor status or inherent therapeutic resistance. The conjugate targeted and suppressed xenograft tumor formation without harming normal cells of the host. In cancer cells, DZ-SIM was enriched in subcellular organelles, including mitochondria, where the conjugate formed adducts with multiple proteins and caused the loss of transmembrane potential, promoting cell death. The DZ-SIM specifically targets PC cells and their mitochondria, resulting in a loss of mitochondrial function and cell death. With a unique subcellular targeting strategy, the conjugate holds the potential to outperform existing chemotherapeutic drugs. It presents a novel strategy to circumvent therapeutic resistance, offering a more potent treatment for mCRPC. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://figshare.com/articles/journal_contribution/Overcoming_Resistance_in_Prostate_Cancer_Therapy_Using_a_DZ-Simvastatin_Conjugate/25010573Test |
| DOI: | 10.1021/acs.molpharmaceut.3c00993.s001 |
| الإتاحة: | https://doi.org/10.1021/acs.molpharmaceut.3c00993.s001Test https://figshare.com/articles/journal_contribution/Overcoming_Resistance_in_Prostate_Cancer_Therapy_Using_a_DZ-Simvastatin_Conjugate/25010573Test |
| حقوق: | CC BY-NC 4.0 |
| رقم الانضمام: | edsbas.371EA266 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.molpharmaceut.3c00993.s001 |
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