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Micheliolide derivative DMAMCL inhibits glioma cell growth in vitro and in vivo.

An Y, Guo W, Li L, Xu C, Yang D, Wang S, Lu Y, Zhang Q, Zhai J, Fan H, Qiu C, Qi J, Chen Y, Yuan S - PLoS ONE (2015)

Bottom Line: DAMMCL down-regulated the anti-apoptosis gene Bcl-2 and increased apoptosis in C6 and U-87MG cells in a dose-dependent manner.Distribution analysis showed that the DMAMCL concentration was higher in the brain than in plasma.Evaluations for toxicity revealed that oral administration of DMAMCL at 200 or 300 mg/kg once a day for 21 days did not result in toxicity.

View Article: PubMed Central - PubMed

Affiliation: Clinical Laboratory Center, Chinese PLA Air Force General Hospital, Haidian, Beijing 100142, PR China.

ABSTRACT

Background: There is no highly effective chemotherapy for malignant gliomas to date. We found that dimethylaminomicheliolide (DMAMCL), a selective inhibitor of acute myeloid leukemia (AML) stem/progenitor cells, inhibited the growth of glioma cells.

Methods: The distribution of DMAMCL in brain was analyzed by an ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS) system. The anti-tumor evaluations of DMAMCL in vitro were performed by MTT, FACS and RT-PCR. In vivo, the mixture of C6 cells and matrigel was injected into caudatum, and the anti-tumor activity of DMAMCL was evaluated by tumor growth and rat survival. The toxicity of DMAMCL was evaluated by body weight, daily food intake, hematological or serum biochemical analyses, and histological appearance of tissues.

Results: The IC50 values of DMAMCL against the C6 and U-87MG cell lines in vitro were 27.18 ± 1.89 μM and 20.58 ± 1.61 μM, respectively. DAMMCL down-regulated the anti-apoptosis gene Bcl-2 and increased apoptosis in C6 and U-87MG cells in a dose-dependent manner. In a C6 rat tumor model, daily administration of DMAMCL for 21 days reduced the burden of C6 tumors by 60% to 88% compared to controls, and more than doubled the mean lifespan of tumor-bearing rats. Distribution analysis showed that the DMAMCL concentration was higher in the brain than in plasma. Evaluations for toxicity revealed that oral administration of DMAMCL at 200 or 300 mg/kg once a day for 21 days did not result in toxicity.

Conclusions: These results suggest that DMAMCL is highly promising for the treatment of glioma.

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Related in: MedlinePlus

HE staining of brains from tumor-bearing rats after treatment for 21 days.All images are representative images, and scale bars indicate 100 μm.
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pone.0116202.g006: HE staining of brains from tumor-bearing rats after treatment for 21 days.All images are representative images, and scale bars indicate 100 μm.

Mentions: The results of the histopathological analysis of animals treated with NS, VCR, or DMAMCL are shown in Fig. 6. The pictures are derived from ipsi lateral. The vehicle group exhibited substantial tumor cell in the brain tissue, sparse pink cytoplasm, densely stained round or oval vesicular nuclei, and atypical mitotic features. As the concentration of DMAMCL increased, the number of tumor cells in rat brain decreased. The brain tissues of animals treated with VCR or DMAMCL at 100 mg/kg appeared similar to normal brain tissues by histopathologic analysis.


Micheliolide derivative DMAMCL inhibits glioma cell growth in vitro and in vivo.

An Y, Guo W, Li L, Xu C, Yang D, Wang S, Lu Y, Zhang Q, Zhai J, Fan H, Qiu C, Qi J, Chen Y, Yuan S - PLoS ONE (2015)

HE staining of brains from tumor-bearing rats after treatment for 21 days.All images are representative images, and scale bars indicate 100 μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4320118&req=5

pone.0116202.g006: HE staining of brains from tumor-bearing rats after treatment for 21 days.All images are representative images, and scale bars indicate 100 μm.
Mentions: The results of the histopathological analysis of animals treated with NS, VCR, or DMAMCL are shown in Fig. 6. The pictures are derived from ipsi lateral. The vehicle group exhibited substantial tumor cell in the brain tissue, sparse pink cytoplasm, densely stained round or oval vesicular nuclei, and atypical mitotic features. As the concentration of DMAMCL increased, the number of tumor cells in rat brain decreased. The brain tissues of animals treated with VCR or DMAMCL at 100 mg/kg appeared similar to normal brain tissues by histopathologic analysis.

Bottom Line: DAMMCL down-regulated the anti-apoptosis gene Bcl-2 and increased apoptosis in C6 and U-87MG cells in a dose-dependent manner.Distribution analysis showed that the DMAMCL concentration was higher in the brain than in plasma.Evaluations for toxicity revealed that oral administration of DMAMCL at 200 or 300 mg/kg once a day for 21 days did not result in toxicity.

View Article: PubMed Central - PubMed

Affiliation: Clinical Laboratory Center, Chinese PLA Air Force General Hospital, Haidian, Beijing 100142, PR China.

ABSTRACT

Background: There is no highly effective chemotherapy for malignant gliomas to date. We found that dimethylaminomicheliolide (DMAMCL), a selective inhibitor of acute myeloid leukemia (AML) stem/progenitor cells, inhibited the growth of glioma cells.

Methods: The distribution of DMAMCL in brain was analyzed by an ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS) system. The anti-tumor evaluations of DMAMCL in vitro were performed by MTT, FACS and RT-PCR. In vivo, the mixture of C6 cells and matrigel was injected into caudatum, and the anti-tumor activity of DMAMCL was evaluated by tumor growth and rat survival. The toxicity of DMAMCL was evaluated by body weight, daily food intake, hematological or serum biochemical analyses, and histological appearance of tissues.

Results: The IC50 values of DMAMCL against the C6 and U-87MG cell lines in vitro were 27.18 ± 1.89 μM and 20.58 ± 1.61 μM, respectively. DAMMCL down-regulated the anti-apoptosis gene Bcl-2 and increased apoptosis in C6 and U-87MG cells in a dose-dependent manner. In a C6 rat tumor model, daily administration of DMAMCL for 21 days reduced the burden of C6 tumors by 60% to 88% compared to controls, and more than doubled the mean lifespan of tumor-bearing rats. Distribution analysis showed that the DMAMCL concentration was higher in the brain than in plasma. Evaluations for toxicity revealed that oral administration of DMAMCL at 200 or 300 mg/kg once a day for 21 days did not result in toxicity.

Conclusions: These results suggest that DMAMCL is highly promising for the treatment of glioma.

Show MeSH
Related in: MedlinePlus