Curcumin inhibited the growth and invasion of human monocytic leukaemia SHI-1 cellsin vivoby altering MAPK and MMP signalling

Abstract

Context: Curcumin, a polyphenolic compound extracted from the rhizome of the tropical plant Curcuma longa L. (Zingiberaceae), has been considered as a cancer chemopreventive drug by American National Cancer Institute. Objective: To examine the effect of curcumin on acute monocytic leukaemia SHI-1 cells in vivo. Materials and methods: The SHI-1 cells (1 Â 10 6 cells in 0.1 mL PBS) were injected subcutaneously into the right flanks of the female SCID mice. Curcumin dissolved in olive oil (15 and 30 mg/kg) was administered (i.p.) to mice once a day for 15 days while the control group received olive oil injection. Tumour proliferation and apoptosis were examined by PCNA, TUNEL and cleaved caspase-3 staining. The expression of MAPK, NF-jB, MMP9, MMP2 and vimentin were confirmed by RT-PCR, immunohistochemistry or western blotting. Results: Administration of curcumin significantly inhibited tumour growth, as the tumour weight decreased from 0.67 g (control) to 0.47 g (15 mg/kg) and 0.35 g (30 mg/kg). Curcumin inhibited the expression of PCNA and increased the degree of TUNEL and cleaved caspase-3 staining in tumour tissue. The results of western blotting showed that curcumin treatment inhibited NF-jB and ERK signalling while activating p38 and JNK. Moreover, curcumin attenuated the mRNA transcription and protein expression of MMP2 and MMP9. Curcumin also suppressed the level of vimentin. Discussion and conclusions: Our study demonstrates that curcumin can inhibit the growth and invasion of human monocytic leukaemia in vivo, suggesting the possible use of curcumin for anti-metastasis in leukaemia and the value of determining its unique target.

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“…A recent study provided in vivo evidence confirming its effect on the apoptosis and invasion of human acute leukemia SHI-1 cells, through activation of JNK and p38 and inhibition of ERK and NF-κB signals. Furthermore, CUR may also downregulate the expression of MMP9 and MMP2 as well as vimentin, leading to suppression of the metastatic potency of SHI-1 (70).…”

Biocompatibility of Bone Marrow-Derived Mesenchymal Stem Cells in the Rat Inner Ear following Trans-Tympanic Administration

“…Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assays are used to detect cells in the late stages of apoptosis, after they have undergone DNA fragmentation and degradation by endonucleases [79][80][81]. This produces DNA fragments with double-stranded breaks and produces the characteristic "laddering" pattern visualized by gel electrophoresis.…”

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“…Curcumin treatment can be involved in the downregulation of NF-kB and ERK signals, and simultaneously activate p38 and JNK. And curcumin would attenuate the expression levels of MMP2, MMP9 and vimentin to affect the EMT process (89). Curcumin has also been shown to inhibit the growth of human A549 lung adenocarcinoma cells and induce apoptosis with a dose-dependent manner.…”