Plant-derived flavone Apigenin: The small-molecule with promising activity against therapeutically resistant prostate cancer

被引:38
作者
Ganai, Shabir Ahmad [1 ]
机构
[1] Univ Kashmir, Dept Biotechnol, Srinagar 190006, Jammu & Kashmir, India
关键词
Apigenin; HATs; HDACs; HDACi; Prostate cancer; Flavonoid; HISTONE DEACETYLASE INHIBITORS; PROTEASOMAL DEGRADATION; CELL-GROWTH; APOPTOSIS; EXPRESSION; SULFORAPHANE; ACTIVATION; CARCINOMA; MIGRATION; THERAPY;
D O I
10.1016/j.biopha.2016.11.130
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Prostate cancer is the second leading cause of cancer related deaths in men in the United States. Mounting evidences suggest that in the pathophysiology of prostate cancer epigenetic modifications play a considerable role. Histone deacetylases (HDACs) have strong crosstalk with prostate cancer progression as they regulate various genes meant for tumour suppression. HDACs are emerging as striking molecular targets for anticancer drugs and therapy as their aberrant expression has been implicated in several cancers. Histone deacetylase inhibitors (HDACi), the small molecules interfering HDACs are the propitious chemotherapeutic agents as they tune the altered acetylation homeostasis for attenuating disease signalling. More than 20 HDACi have entered into the clinical trials and 4 have crossed the journey by gaining FDA approval for treating distinct haematological malignancies including multiple myeloma. Despite the therapeutic benefits, the synthetic HDACi cause detrimental side effects like atrial fibrillation, raising concerns regarding their applicability. Taking these facts into consideration the current article focused on plant-derived HDAC inhibitor Apigenin and its marvelous role in prostate cancer therapy. Moreover, the article sheds light on Apigenin induced apoptosis in various prostate cancer models. The defined inhibitor provokes apoptotic signaling in these models by multiple mechanisms like restraining HDACs, declining the levels of antiapoptotic proteins. Importantly, Apigenin hampers NF-kappa B signalling and down-modulates its regulated gene products for bringing therapeutic effect. Furthermore, Apigenin shows synergistic effect in combinatorial therapy and induces apoptosis even in prostate cancer models resistant to conventional therapeutic regimens. (C) 2016 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:47 / 56
页数:10
相关论文
共 70 条
[1]   The role of histone deacetylases in prostate cancer [J].
Abbas, Ata ;
Gupta, Sanjay .
EPIGENETICS, 2008, 3 (06) :300-309
[2]  
[Anonymous], 2016, 2016 IEEEOES CHINA O, DOI DOI 10.1109/COA.2016.7535678
[3]  
[Anonymous], ANTICANCER AGENTS ME
[4]   Intracellular trafficking of histone deacetylase 4 regulates neuronal cell death [J].
Bolger, TA ;
Yao, TP .
JOURNAL OF NEUROSCIENCE, 2005, 25 (41) :9544-9553
[5]   Cloning and characterization of a novel human histone deacetylase, HDAC8 [J].
Buggy, JJ ;
Sideris, ML ;
Mak, P ;
Lorimer, DD ;
McIntosh, B ;
Clark, JM .
BIOCHEMICAL JOURNAL, 2000, 350 :199-205
[6]   Inhibition of proteasome activity by the dietary flavonoid apigenin is associated with growth inhibition in cultured breast cancer cells and xenografts [J].
Chen, Di ;
Landis-Piwowar, Kristin R. ;
Chen, Marina S. ;
Dou, Q. Ping .
BREAST CANCER RESEARCH, 2007, 9 (06)
[7]   A neuroprotective herbal mixture inhibits caspase-3-independent apoptosis in retinal ganglion cells [J].
Cheung, Zelda H. ;
Leung, Mason C. P. ;
Yip, Henry K. ;
Wu, Wutian ;
Siu, Flora K. W. ;
So, Kwok-Fai .
CELLULAR AND MOLECULAR NEUROBIOLOGY, 2008, 28 (01) :137-155
[8]   5-Fluorouracil combined with apigenin enhances anticancer activity through induction of apoptosis in human breast cancer MDA-MB-453 cells [J].
Choi, Eun Jeong ;
Kim, Gun-Hee .
ONCOLOGY REPORTS, 2009, 22 (06) :1533-1537
[9]   Apigenin Induces Apoptosis through a Mitochondria/Caspase-Pathway in Human Breast Cancer MDA-MB-453 Cells [J].
Choi, Eun Jeong ;
Kim, Gun-Hee .
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION, 2009, 44 (03) :260-265
[10]   Regulation of class IIa HDAC activities: it is not only matter of subcellular localization [J].
Di Giorgio, Eros ;
Brancolini, Claudio .
EPIGENOMICS, 2016, 8 (02) :251-269