Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer.
Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer.
复制标题
DOI：
10.1016/j.semcancer.2016.06.003
复制
发表时间：
2016-10
影响因子：
14.5
通讯作者：
Lokeshwar BL
中科院分区：
文献类型：
--
作者：
Kallifatidis G;Hoy JJ;Lokeshwar BL
前列腺癌（PCa）是一种激素驱动的癌症，在大多数西方工业化国家的男性癌症发病率中排名第一，在癌症相关死亡率中排名第二。雄激素和雄激素受体（AR）是前列腺癌生长的主要调节剂。在过去的二十年中，前列腺癌的筛查、治疗、监测和姑息治疗取得了多项进展，显著提高了诊断后的生活质量和生存率。然而，超过20%最初诊断为PCa的患者仍然发展为侵袭性和治疗难治性疾病。使用来自海绵、蘑菇和可食用植物的生物活性化合物作为现有治疗的单一药物或辅助剂来预防或治疗激素难治性PCa，在临床上尚未取得成功。在天然产物现有分子结构的鉴定、测试和修饰方面取得了重大进展。此外，这些化合物与新基质的结合提高了它们的生物利用度；这是将天然产品用于临床试验的一大步。从可食用植物中提取的天然产品（营养保健品）和普通的民间药物可能比合成化合物具有优势，因为它们的靶点范围更广，与大多数单一靶点的合成抗癌化合物相比；例如，激酶抑制剂。使用针对癌细胞中单个异常分子的合成抑制剂或抗体可能是治疗难治性癌症出现的部分原因。靶向AR信号传导（表没食子儿茶素没食子酸酯[EGCG]、姜黄素和5α-还原酶抑制剂）、AR合成（灯叶素、辣椒素等）或AR降解（白桦酸、二吲哚酰二胺、硫萝卜素、水水蓟宾等）的营养药品是用作辅助或单一治疗的主要候选药物。营养药品针对癌症发生和发展过程中涉及的多种病理生理机制，因此有可能同时抑制前列腺癌的生长和转移进展（例如，抑制血管生成、上皮-间质转化（EMT）和增殖）。鉴于其多靶点特性以及相对较低的全身毒性，这些化合物在预防和治疗PCa方面具有显著的治疗优势。这篇综述强调了一些研究充分的靶向AR的天然化合物在预防和治疗PCa方面的潜在应用。
Prostate cancer (PCa), a hormonally-driven cancer, ranks first in incidence and second in cancer related mortality in men in most Western industrialized countries. Androgen and androgen receptor (AR) are the dominant modulators of PCa growth. Over the last two decades multiple advancements in screening, treatment, surveillance and palliative care of PCa have significantly increased quality of life and survival following diagnosis. However, over 20% of patients initially diagnosed with PCa still develop an aggressive and treatment-refractory disease. Prevention or treatment for hormone-refractory PCa using bioactive compounds from marine sponges, mushrooms, and edible plants either as single agents or as adjuvants to existing therapy, has not been clinically successful. Major advancements have been made in the identification, testing and modification of the existing molecular structures of natural products. Additionally, conjugation of these compounds to novel matrices has enhanced their bio-availability; a big step towards bringing natural products to clinical trials. Natural products derived from edible plants (nutraceuticals), and common folk-medicines might offer advantages over synthetic compounds due to their broader range of targets, as compared to mostly single target synthetic anticancer compounds; e.g. kinase inhibitors. The use of synthetic inhibitors or antibodies that target a single aberrant molecule in cancer cells might be in part responsible for emergence of treatment refractory cancers. Nutraceuticals that target AR signaling (epigallocatechin gallate [EGCG], curcumin, and 5α-reductase inhibitors), AR synthesis (ericifolin, capsaicin and others) or AR degradation (betulinic acid, di-indolyl diamine, sulphoraphane, silibinin and others) are prime candidates for use as adjuvant or mono-therapies. Nutraceuticals target multiple pathophysiological mechanisms involved during cancer development and progression and thus have potential to simultaneously inhibit both prostate cancer growth and metastatic progression (e.g., inhibition of angiogenesis, epithelial-mesenchymal transition (EMT) and proliferation). Given their multi-targeting properties along with relatively lower systemic toxicity, these compounds offer significant therapeutic advantages for prevention and treatment of PCa. This review emphasizes the potential application of some of the well-researched natural compounds that target AR for prevention and therapy of PCa.
登录
查看更多内容
影响因子：
82.9
作者：
Chen, CD;Welsbie, DS;Sawyers, CL
通讯作者：
Sawyers, CL
影响因子：
64.5
作者：
Chang KH;Li R;Kuri B;Lotan Y;Roehrborn CG;Liu J;Vessella R;Nelson PS;Kapur P;Guo X;Mirzaei H;Auchus RJ;Sharifi N
通讯作者：
Sharifi N
影响因子：
3.7
作者：
Chau CH;Price DK;Till C;Goodman PJ;Chen X;Leach RJ;Johnson-Pais TL;Hsing AW;Hoque A;Tangen CM;Chu L;Parnes HL;Schenk JM;Reichardt JK;Thompson IM;Figg WD
通讯作者：
Figg WD
影响因子：
3
作者：
Amato, Robert;Stepankiw, Mika;Gonzales, Patricia
通讯作者：
Gonzales, Patricia
影响因子：
50.3
作者：
Andersen, Raymond J.;Mawji, Nasrin R.;Sadar, Marianne D.
通讯作者：
Sadar, Marianne D.