A ndrographolide inhibits hypoxia-inducible factor-1 through phosphatidylinositol 3-kinase/AKT pathway and suppresses breast cancer growth

被引：55

作者：

Li, Jie ^{[1
]}

Zhang, Chao ^{[1
]}

Jiang, Hongchuan ^{[1
]}

Cheng, Jiao ^{[2
]}

机构：

[1] Beijing Chao Yang Hosp, Dept Gen Surg, Beijing 100020, Peoples R China

[2] Beijing Chao Yang Hosp, Dept Gynecol & Obstet, Beijing 100020, Peoples R China

来源：

ONCOTARGETS AND THERAPY | 2015年 / 8卷

关键词：

Andrographolide (Andro); HIF-1; alpha; inhibit; breast cancer; hypoxia; PI3k/AKT/mTOR pathway; ANDROGRAPHIS-PANICULATA; TUMOR PROGRESSION; SIGNALING PATHWAY; FACTOR EXPRESSION; CELLS; HIF-1; THERAPY; APOPTOSIS;

D O I：

10.2147/OTT.S76116

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

Hypoxia-inducible factor-1 (HIF-1) is a master regulator of the transcriptional response to hypoxia. HIF-1 alpha is one of the most compelling anticancer targets. Andrographolide (Andro) was newly identified to inhibit HIF-1 in T47D cells (a half maximal effective concentration [EC50] of 1.03x10-7 mol/L), by a dual-luciferase reporter assay. It suppressed HIF-1 alpha protein and gene accumulation, which was dependent on the inhibition of upstream phosphatidylinositol 3-kinase (PI3K)/AKT pathway. It also abrogated the expression of HIF-1 target vascular endothelial growth factor (VEGF) gene and protein. Further, Andro inhibited T47D and MDA-MB-231 cell proliferation and colony formation. In addition, it exhibited significant in vivo efficacy and antitumor potential against the MDA-MB-231 xenograft in nude mice. In conclusion, these results highlighted the potential effects of Andro, which inhibits HIF-1, and hence may be developed as an antitumor agent for breast cancer therapy in future.

引用

页码：427 / 435

页数：9

共 29 条

[1]

Regulation of HIF prolyl hydroxylases by hypoxia-inducible factors [J].

Aprelikova, O ;

Chandramouli, GVR ;

Wood, M ;

Vasselli, JR ;

Riss, J ;

Maranchie, JK ;

Linehan, WM ;

Barrett, JC .

JOURNAL OF CELLULAR BIOCHEMISTRY, 2004, 92 (03) :491-501

[2]

Brahimi-Horn MC, 2005, INT REV CYTOL, V242, P157

[3]

Andrographolide isolated from Andrographis paniculata induces cell cycle arrest and mitochondrial-mediated apoptosis in human leukemic HL-60 cells [J].

Cheung, HY ;

Cheung, SH ;

Li, JL ;

Cheung, CS ;

Lai, WP ;

Fong, WF ;

Leung, FM .

PLANTA MEDICA, 2005, 71 (12) :1106-1111

[4]

Forsythe JA, 1996, MOL CELL BIOL, V16, P4604

[5]

Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells [J].

Fukuda, R ;

Hirota, K ;

Fan, F ;

Do Jung, Y ;

Ellis, LM ;

Semenza, GL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (41) :38205-38211

[6]

Gilkes DM, 2013, FUTURE ONCOL, V9, P1623, DOI [10.2217/fon.13.92, 10.2217/FON.13.92]

[7]

Hypoxia - A key regulatory factor in tumour growth [J].

Harris, AL .

NATURE REVIEWS CANCER, 2002, 2 (01) :38-47

[8]

AKT signaling in regulating angiogenesis [J].

Jiang, Bing-Hua ;

Liu, Ling-Zhi .

CURRENT CANCER DRUG TARGETS, 2008, 8 (01) :19-26

[9]

A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth [J].

Lang, Liwei ;

Liu, Xiaoyu ;

Li, Yan ;

Zhou, Qing ;

Xie, Ping ;

Yan, Chunhong ;

Chen, Xiaoguang .

PLOS ONE, 2014, 9 (06)

[10]

HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1α (HIF-1α) synthesis:: Novel mechanism for HIF-1-mediated vascular endothelial growth factor expression [J].

Laughner, E ;

Taghavi, P ;

Chiles, K ;

Mahon, PC ;

Semenza, GL .

MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (12) :3995-4004

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