Yoon, Jae-Hwan
(Department of Bioscience and Biotechnology, Research Institute of Bioactive-Metabolome Network, Konkuk University)
,
Pham, Thu-Huyen
(Department of Bioscience and Biotechnology, Research Institute of Bioactive-Metabolome Network, Konkuk University)
,
Lee, Jintak
(Department of Bioscience and Biotechnology, Research Institute of Bioactive-Metabolome Network, Konkuk University)
,
Lee, Jiyon
(Department of Bioscience and Biotechnology, Research Institute of Bioactive-Metabolome Network, Konkuk University)
,
Ryu, Hyung-Won
(Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology)
,
Oh, Sei-Ryang
(Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology)
,
Oh, Jae-Wook
(Department of Stem Cell and Regenerative Biotechnology, Konkuk University)
,
Yoon, Do-Young
(Department of Bioscience and Biotechnology, Research Institute of Bioactive-Metabolome Network, Konkuk University)
Methyl linderone (ML), a cyclo-pentenedione, was isolated from the fruit of Lindera erythrocarpa Makino (family Lauraceae). This plant has well-known anti-inflammatory effects; however, the anti-cancer effects of ML have not yet been reported. Thus, in the present study we investigated the effects o...
Methyl linderone (ML), a cyclo-pentenedione, was isolated from the fruit of Lindera erythrocarpa Makino (family Lauraceae). This plant has well-known anti-inflammatory effects; however, the anti-cancer effects of ML have not yet been reported. Thus, in the present study we investigated the effects of ML on the metastasis of human breast cancer cells. We used 12-O-tetradecanoyl phorbol-13-acetate (TPA)-stimulated MCF-7 cells as the cell model to study the effects of ML on invasion and migration. ML was found to reduce the invasion and migration rate of TPA-stimulated MCF-7 cells. Moreover, it inhibited two metastasis-related factors, matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8), at the mRNA and protein expression levels, in TPA-treated MCF-7 cells. The mechanism by which ML exerted these effects was through the inhibition of translocation of activator protein-1 (AP-1) and signal transducer and activator of transcription-3 (STAT3), mediated via phosphorylation of extracellular signal-regulated kinase (ERK). Taken together, our findings indicated that ML attenuated the TPA-stimulated invasion and migration of MCF-7 cells by suppressing the phosphorylation of ERK and its downstream factors, AP-1 and STAT3. Therefore, ML is a potential agent for the treatment of breast cancer metastasis.
Methyl linderone (ML), a cyclo-pentenedione, was isolated from the fruit of Lindera erythrocarpa Makino (family Lauraceae). This plant has well-known anti-inflammatory effects; however, the anti-cancer effects of ML have not yet been reported. Thus, in the present study we investigated the effects of ML on the metastasis of human breast cancer cells. We used 12-O-tetradecanoyl phorbol-13-acetate (TPA)-stimulated MCF-7 cells as the cell model to study the effects of ML on invasion and migration. ML was found to reduce the invasion and migration rate of TPA-stimulated MCF-7 cells. Moreover, it inhibited two metastasis-related factors, matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8), at the mRNA and protein expression levels, in TPA-treated MCF-7 cells. The mechanism by which ML exerted these effects was through the inhibition of translocation of activator protein-1 (AP-1) and signal transducer and activator of transcription-3 (STAT3), mediated via phosphorylation of extracellular signal-regulated kinase (ERK). Taken together, our findings indicated that ML attenuated the TPA-stimulated invasion and migration of MCF-7 cells by suppressing the phosphorylation of ERK and its downstream factors, AP-1 and STAT3. Therefore, ML is a potential agent for the treatment of breast cancer metastasis.
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제안 방법
However, the anti-migratory and anti-invasive effects of ML have not yet been fully examined. In this study, we evaluated the anti-metastatic effects and investigated the underlying mechanisms of ML in TPA-stimulated MCF-7 breast cancer cells.
Therefore, non-cytotoxic concentrations of ML up to 10 μM were used in subsequent experiments, to study its anti-invasive and anti-migratory effects.
데이터처리
One-way analysis of variance, followed by Tukey’s HSD test, were used to evaluate differences between groups.
이론/모형
After pretreatment, cells were treated with TPA (50 nM) in the presence or absence of ML. Cell viability was assessed using an MTS assay. Results represent the mean ± SD of three experiments.
성능/효과
In conclusion, ML significantly downregulated MMP-9 and IL-8 expression in TPA-stimulated MCF7 cells, by inhibiting the ERK/STAT3/AP-1-mediated signaling pathway. These results suggested that ML is a potential pharmacological agent for breast cancer treatment, to block cancer invasion and migration.
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