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Cancer Chemotherapy and Pharmacology

Published in:

01-06-2012 | Original Article

RY10-4, a novel anti-tumor compound, exhibited its anti-angiogenesis activity by down-regulation of the HIF-1α and inhibition phosphorylation of AKT and mTOR

Authors: Ziwei Liu, Qianying Yuan, Xuenong Zhang, Chaomei Xiong, Pingping Xue, Jinlan Ruan

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2012

Abstract

Purpose

To assess the anti-angiogenesis potential and mechanism of RY10-4, a derivative of protoapigenone, which was verified the broad-spectrum anti-tumor activities by previous study.

Methods

RY10-4 and RY10-3 were synthesized according to the procedure described. Breast cancer cells MCF-7 and MDA-MB-231 that got the best performance in the previous anti-tumor activity screening were selected for further anti-cancer mechanism research. Firstly, cells proliferation assay of RY10-4 and RY10-3 was used to demonstrate the fact that the 4-hydroxy-2,5-cyclohexadien-1-one system would be the efficient pharmacophore of RY10-4. Then, a series of assays such as human umbilical vein endothelial cells (HUVECs) proliferation assay, HUVECs migration, tube network formation and morphological observations of zebrafish were applied to confirm its anti-angiogenesis activity. Upon RY10-4 treatment, the HIF-1α and VEGF were analyzed by western blot in normoxic and hypoxic conditions, meanwhile the PI3K-AKT-mTOR pathway-related protein such as AKT, p-AKT, mTOR and p-mTOR was also analyzed.

Results

In the MCF-7, MDA-MB-231 and HUVECs proliferation assay, RY10-4 that has 4-hydroxy-2,5-cyclohexadien-1-one system showed distinct advantage compared with RY10-3. Tests had verified the anti-angiogenesis capability of RY10-4. Down-regulation of the HIF-1α and inhibition phosphorylation levels of AKT and mTOR were found to be the pathway that RY10-4 exerts its functions on anti-angiogenesis.

Conclusions

The structure of 4-hydroxy-2,5-cyclohexadien-1-one should be the effective pharmacophore of RY10-4. RY10-4 got fine performance in anti-tumor and anti-angiogenesis assay, and thus, the quinol compound will be the new hot-spot for further anti-tumor agency development.

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Title: RY10-4, a novel anti-tumor compound, exhibited its anti-angiogenesis activity by down-regulation of the HIF-1α and inhibition phosphorylation of AKT and mTOR
Authors: Ziwei Liu
Qianying Yuan
Xuenong Zhang
Chaomei Xiong
Pingping Xue
Jinlan Ruan
Publication date: 01-06-2012
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2012
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-012-1873-3

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Abstract

Purpose

Methods

Results

Conclusions

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