Please use this identifier to cite or link to this item: https://doi.org/10.4161/auto.8.3.18721
Title: Andrographolide sensitizes cisplatin-induced apoptosis via suppression of autophagosome-lysosome fusion in human cancer cells
Authors: Zhou, J. 
Hu, S.-E.
Tan, S.-H.
Cao, R.
Chen, Y.
Xia, D.
Zhu, X.-Q.
Yang, X.-F.
Ong, C.-N. 
Shen, H.-M. 
Keywords: Andrographolide
Apoptosis
Autophagy
Lysosomes
Sensitization
Issue Date: Mar-2012
Source: Zhou, J., Hu, S.-E., Tan, S.-H., Cao, R., Chen, Y., Xia, D., Zhu, X.-Q., Yang, X.-F., Ong, C.-N., Shen, H.-M. (2012-03). Andrographolide sensitizes cisplatin-induced apoptosis via suppression of autophagosome-lysosome fusion in human cancer cells. Autophagy 8 (3) : 338-349. ScholarBank@NUS Repository. https://doi.org/10.4161/auto.8.3.18721
Abstract: Suppression of autophagy has been increasingly recognized as a novel cancer therapeutic approach. Andrographolide (Andro), a diterpenoid lactone isolated from an herbal plant Andrographis paniculata, is known to possess anti-inflammatory and anticancer activity. In this study, we sought to examine the effect of Andro on autophagy, and to evaluate whether such effect is relevant to the sensitization effect of Andro on apoptosis induced by DNA damage agents in cancer cells. First, we found that Andro is able to significantly enhance autophagic markers in various cancer cell lines, including GFP-LC3 puncta and LC3-II level. Interestingly, Andro treatment also led to marked increase of p62 protein level and addition of chloroquine (CQ) failed to further enhance either LC3-II or p62 level, indicating that Andro is likely to suppress autophagic flux at the maturation and degradation stage. Next, we provided evidence that Andro inhibits autophagosome maturation not by affecting the lysosomal function, but by impairing autophagosome-lysosome fusion. Lastly, we demonstrated that treatment with cisplatin, a DNA damage agent, induces autophagy in cancer cells. Importantly, Andro is capable of sensitizing cisplatin-induced cell killing determined with both short-term apoptosis assays and long-term clonogenic test, via suppression of autophagy, a process independent of p53. In summary, these observations collectively suggest that Andro could be a promising anti-cancer agent in combination therapy via its potent inhibitory effect on autophagy by disrupting autophagosome-lysosome fusion. © 2012 Landes Bioscience.
Source Title: Autophagy
URI: http://scholarbank.nus.edu.sg/handle/10635/108870
ISSN: 15548627
DOI: 10.4161/auto.8.3.18721
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

42
checked on Feb 14, 2018

WEB OF SCIENCETM
Citations

36
checked on Jan 16, 2018

Page view(s)

39
checked on Feb 18, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.