Back to Search
Start Over
Andrographolide causes apoptosis via inactivation of STAT3 and Akt and potentiates antitumor activity of gemcitabine in pancreatic cancer.
- Source :
-
Toxicology letters [Toxicol Lett] 2013 Sep 12; Vol. 222 (1), pp. 23-35. Date of Electronic Publication: 2013 Jul 08. - Publication Year :
- 2013
-
Abstract
- Gemcitabine is a first-line drug utilised in the chemotherapy of pancreatic cancer; however, this drug induces chemo-resistance and toxicity to normal tissue during treatment. Here, we firstly report that andrographolide (ANDRO) alone not only has anti-pancreatic cancer activity, but it also potentiates the anti-tumour activity of gemcitabine. Treatment with ANDRO alone inhibits proliferation of the pancreatic cancer cell lines in a dose- and time-dependent manner in vitro. Interestingly, ANDRO induces cell cycle arrest and apoptosis of pancreatic cancer cells by inhibiting STAT3 and Akt activation, upregulating the expression of p21(WAF1) and Bax, and downregulating the expression of cyclinD1, cyclinE, survivin, X-IAP and Bcl-2. Additionally, ANDRO combined with gemcitabine significantly induce stronger cell cycle arrest and more obvious apoptosis than each single treatment. The mechanistic study demonstrates that this synergistic effect is also dependent on the inhibition of STAT3 and Akt activations which subsequently regulates the pathways involved in the apoptosis and cell cycle arrest. Furthermore, both ANDRO alone and the combination treatments exhibit efficacious anti-tumour activity in vivo. Overall, our results provide solid evidence supporting that ANDRO alone or its combination with gemcitabine is a potential chemotherapeutic approach for treating human pancreatic cancer in clinical practice.<br /> (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Animals
Blotting, Western
Cell Count
Cell Cycle drug effects
Cell Line, Tumor
Coloring Agents
Cytochromes c metabolism
Deoxycytidine therapeutic use
Drug Synergism
Flow Cytometry
Gentian Violet
Humans
Ki-67 Antigen
Male
Mice
Mice, Inbred BALB C
Xenograft Model Antitumor Assays
Gemcitabine
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Antimetabolites, Antineoplastic therapeutic use
Apoptosis drug effects
Deoxycytidine analogs & derivatives
Diterpenes pharmacology
Pancreatic Neoplasms drug therapy
Proto-Oncogene Proteins c-akt antagonists & inhibitors
STAT3 Transcription Factor antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3169
- Volume :
- 222
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Toxicology letters
- Publication Type :
- Academic Journal
- Accession number :
- 23845849
- Full Text :
- https://doi.org/10.1016/j.toxlet.2013.06.241