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Curcumin: a double hit on malignant mesothelioma.
- Source :
-
Cancer prevention research (Philadelphia, Pa.) [Cancer Prev Res (Phila)] 2014 Mar; Vol. 7 (3), pp. 330-40. Date of Electronic Publication: 2014 Jan 15. - Publication Year :
- 2014
-
Abstract
- Inflammation is a key mediator in the development of malignant mesothelioma, which has a dismal prognosis and poor therapeutic strategies. Curcumin, a naturally occurring polyphenol in turmeric, has been shown to possess anticarcinogenic properties through its anti-inflammatory effects. Inflammasomes, a component of inflammation, control the activation of caspase-1 leading to pyroptosis and processing of proinflammatory cytokines, interleukin (IL)-1β and IL-18. In the present study, we investigate the role of curcumin in pyroptotic cell death of malignant mesothelioma cells. Using in vitro models with mouse and human malignant mesothelioma cells, curcumin is shown to induce pyroptosis through activation of caspase-1 and increased release of high-mobility group box 1 (HMGB1) without processing of IL-1β and IL-18. Absence of IL-1β processing in response to curcumin-mediated caspase-1 activation is attributed to blockade of pro-IL-1β priming through inhibition of the NF-κB pathway. Furthermore, curcumin's cytotoxicity in malignant mesothelioma cells is demonstrated to be dependent on pyroptosis as inhibition of caspase-1 resulted in protection against curcumin-induced cell death. We also demonstrate that curcumin-mediated caspase-1 activation is oxidant dependent by using N-acetyl-L-cysteine (NAC) to inhibit pyroptosis. PCR array analysis using the human inflammasome template revealed that curcumin significantly downregulated levels of inflammasome-related gene expression involved in inflammation, e.g., NF-κB, toll-like receptors (TLR), and IL-1β. Our data indicate that curcumin has a double effect on malignant mesothelioma cells through induction of pyroptosis while subsequently protecting against inflammation.
- Subjects :
- Animals
Apoptosis genetics
Carrier Proteins antagonists & inhibitors
Carrier Proteins genetics
Carrier Proteins metabolism
Caspase 1 metabolism
Cytokines metabolism
Humans
Inflammasomes genetics
Inflammasomes metabolism
Lung Neoplasms metabolism
Mesothelioma metabolism
Mesothelioma, Malignant
Mice
NLR Family, Pyrin Domain-Containing 3 Protein
RNA, Small Interfering pharmacology
Reactive Oxygen Species metabolism
Signal Transduction drug effects
Tumor Cells, Cultured
Apoptosis drug effects
Curcumin pharmacology
Inflammasomes drug effects
Lung Neoplasms immunology
Lung Neoplasms pathology
Mesothelioma immunology
Mesothelioma pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1940-6215
- Volume :
- 7
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cancer prevention research (Philadelphia, Pa.)
- Publication Type :
- Academic Journal
- Accession number :
- 24431405
- Full Text :
- https://doi.org/10.1158/1940-6207.CAPR-13-0259