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Pharm Biol. 2016 Aug;54(8):1303-11. doi: 10.3109/13880209.2015.1060508. Epub 2015 Jul 1.

Curcumin induces apoptosis and suppresses invasion through MAPK and MMP signaling in human monocytic leukemia SHI-1 cells.

Author information

1
a First Clinical College, Nanjing University of Chinese Medicine , Nanjing , China .
2
b Leukemia Research Unit, Jiangsu Institute of Hematology, 1st Affiliated Hospital of Soochow University , Suzhou , China , and.
3
c Department of Hematology , 1st Affiliated Hospital of Nanjing University of Chinese Medicine , Nanjing , China.

Abstract

CONTEXT:

Curcumin is a polyphenolic compound extracted from rhizomes of the tropical plant Curcuma longa L. (Zingiberaceae) and it has antitumor, antioxidative, and anti-inflammatory effects. However, its effects on leukemia cell proliferation and invasion are not clear.

OBJECTIVE:

This study investigates the effects of curcumin on acute monocytic leukemia SHI-1 cells at the molecular level.

MATERIALS AND METHODS:

The effects of SHI-1 cells treated with 6.25-25 μM curcumin for 12-48 h were measured by MTT assay, flow cytometry, and Matrigel transwell assay; the underlying molecular mechanisms were assessed by quantitative PCR, Western blotting, and gelatin zymography.

RESULTS:

Treatment of SHI-1 cells with curcumin inhibited cell proliferation in a dose- and time-dependent manner, and the IC50 values at 12, 24, and 48 h were 32.40, 14.13, and 9.67 μM. Curcumin inhibited SHI-1 cell proliferation by arresting the cells in the S-phase, increasing the number of Annexin V-FITC(+)/PI(-) cells and promoting the loss of △Ψm. The results of PCR and Western blotting showed that curcumin increased the FasL mRNA level; inhibited Bcl-2, NF-κB, and ERK expression; and activated P38 MAPK, JNK, and caspase-3. Additionally, curcumin partially suppressed SHI-1 cell invasion and attenuated the mRNA transcription and secretion of MMP-2 and MMP-9.

DISCUSSION AND CONCLUSION:

This study demonstrates that curcumin not only induces SHI-1 cell apoptosis, possibly via both intrinsic and extrinsic pathways triggered by JNK, P38 MAPK and ERK signaling, but also partially suppresses SHI-1 cell invasion, likely by reducing the levels of transcription and secretion of MMP-2 and MMP-9.

KEYWORDS:

Antitumor; matrix metalloproteinase; mitogen-activated protein kinase

PMID:
26134921
DOI:
10.3109/13880209.2015.1060508
[Indexed for MEDLINE]

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