Teymouri Manouchehr, Pirro Matteo, Johnston Thomas P, Sahebkar Amirhosein
Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, 91775-1365, Iran.
Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Italy.
Biofactors. 2017 May 6;43(3):331-346. doi: 10.1002/biof.1344. Epub 2016 Nov 29.
Curcumin, the bioactive polyphenolic ingredient of turmeric, has been extensively studied for its effects on human papilloma virus (HPV) infection as well as primary and malignant squamous cervical cancers. HPV infections, especially those related to HPV 16 and 18 types, have been established as the leading cause of cervical cancer; however, there are also additional contributory factors involved in the etiopathogenesis of cervical cancers. Curcumin has emerged as having promising chemopreventive and anticancer effects against both HPV-related and nonrelated cervical cancers. In this review, we first discuss the biological relevance of curcumin and both its pharmacological effects and pharmaceutical considerations from a chemical point of view. Next, the signaling pathways that are modulated by curcumin and are relevant to the elimination of HPV infection and treatment of cervical cancer are discussed. We also present counter arguments regarding the effects of curcumin on signaling pathways and molecular markers dysregulated by benzo(a)pyrene (Bap), a carcinogen found in pathological cervical lesions of women who smoke frequently, and estradiol, as two important risk factors involved in persistent HPV-infection and cervical cancer. Finally, various strategies to enhance the pharmacological activity and pharmacokinetic characteristics of curcumin are discussed with examples of studies in experimental models of cervical cancer. © 2016 BioFactors, 43(3):331-346, 2017.
姜黄素是姜黄中的生物活性多酚成分,其对人乳头瘤病毒(HPV)感染以及原发性和恶性宫颈鳞状细胞癌的影响已得到广泛研究。HPV感染,尤其是与16型和18型HPV相关的感染,已被确认为宫颈癌的主要病因;然而,宫颈癌的发病机制中还存在其他促成因素。姜黄素已显示出对HPV相关和非相关宫颈癌具有有前景的化学预防和抗癌作用。在本综述中,我们首先从化学角度讨论姜黄素的生物学相关性及其药理作用和药学考虑因素。接下来,讨论由姜黄素调节的、与消除HPV感染和治疗宫颈癌相关的信号通路。我们还针对姜黄素对信号通路和分子标志物的影响提出了反驳观点,这些信号通路和分子标志物因苯并(a)芘(Bap,在经常吸烟女性的病理性宫颈病变中发现的一种致癌物)和雌二醇(作为持续HPV感染和宫颈癌的两个重要风险因素)而失调。最后,以宫颈癌实验模型中的研究为例,讨论了增强姜黄素药理活性和药代动力学特征的各种策略。© 2016生物因子,43(3):331 - 346,2017。