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Metformin suppressed the proliferation of LoVo cells and induced a time-dependent metabolic and transcriptional alteration.

He J, Wang K, Zheng N, Qiu Y, Xie G, Su M, Jia W, Li H - Sci Rep (2015)

Bottom Line: An obvious time-dependent metabolic alteration was observed from 8 to 48 h, prior to the reduction of cell viability.Meanwhile, the transcirptomic profile revealed 134 and 3061 differentially expressed genes at 8 and 24 h by metformin.Altogether, our current data indicate that metformin suppressed the proliferation of LoVo cells, which may be due to the modulation on cell energy metabolism at both metabolic and transcriptional levels in a time-dependent way.

View Article: PubMed Central - PubMed

Affiliation: Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

ABSTRACT
Metformin is a widely used anti-diabetic drug with potential anti-tumor activity. However, little is known about its global metabolic and transcriptional impacts on tumor cells. In current study, we performed a metabolic profiling on human-derived colon cancer LoVo cells treated by 10 mM metformin for 8, 24 and 48 h. An obvious time-dependent metabolic alteration was observed from 8 to 48 h, prior to the reduction of cell viability. A total of 47, 45 and 66 differential metabolites were identified between control and metformin-treated cells at three time points. Most of the metabolites were up-regulated at 8 h, but down-regulated at 24 and 48 h by metformin. These metabolites were mainly involved in carbohydrates, lipids, amino acids, vitamins and nucleotides metabolism pathways. Meanwhile, the transcirptomic profile revealed 134 and 3061 differentially expressed genes at 8 and 24 h by metformin. In addition to the cancer signaling pathways, expression of genes involved in cell energy metabolism pathways was significantly altered, which were further validated with genes in glucose metabolism pathway. Altogether, our current data indicate that metformin suppressed the proliferation of LoVo cells, which may be due to the modulation on cell energy metabolism at both metabolic and transcriptional levels in a time-dependent way.

No MeSH data available.


Related in: MedlinePlus

Metabolic profiling of LoVo cells treated with 10 mM metformin for different time points.(A–D) The PCA score plots for all groups, Con 8 h vs Met 8 h, Con 24 h vs Met 24 h, and Con 48 h vs Met 48 h, respectively. (E) The heatmap for the intensity variations of the total 158 metabolites identified with GC/TOFMS and LC/TOFMS together.
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f2: Metabolic profiling of LoVo cells treated with 10 mM metformin for different time points.(A–D) The PCA score plots for all groups, Con 8 h vs Met 8 h, Con 24 h vs Met 24 h, and Con 48 h vs Met 48 h, respectively. (E) The heatmap for the intensity variations of the total 158 metabolites identified with GC/TOFMS and LC/TOFMS together.

Mentions: The metabolic profile was evaluated between control and metformin treated cells at three different time points using unsupervised statistics, PCA on the basis of 158 identified cellular metabolites from GC/TOFMS and LC/TOFMS. The PCA loading plots showed that the cell samples of con 8 h and con 24 h almost clustered together, but were clearly separated from those of con 48 h (Fig. 2A), suggesting the gradual alteration of cellular metabolites with culture time. A similar time-dependent metabolic alteration was also observed in metformin-treated cells (Fig. 2A), which was further characterized by individual comparisons between control and metformin groups at different time points (Fig. 2B–D). To further investigate the impacts of both culture time and metformin treatment, a heatmap among all groups was drawn on the basis of relative intensity of total 158 identified metabolites compared to con 8 h group. Generally, the amount of cellular metabolites was obviously downregulated with culture time either in control or metformin-treated cells. However, most metabolites in met 8 h group were upregulated in comparison with con 8 h, but were further depleted by metformin at 24 h and 48 h (Fig. 2E). These metabolic profiles indicate a time-dependent alteration in amounts of cellular metabolites resulted from culture time and/or metformin treatment.


Metformin suppressed the proliferation of LoVo cells and induced a time-dependent metabolic and transcriptional alteration.

He J, Wang K, Zheng N, Qiu Y, Xie G, Su M, Jia W, Li H - Sci Rep (2015)

Metabolic profiling of LoVo cells treated with 10 mM metformin for different time points.(A–D) The PCA score plots for all groups, Con 8 h vs Met 8 h, Con 24 h vs Met 24 h, and Con 48 h vs Met 48 h, respectively. (E) The heatmap for the intensity variations of the total 158 metabolites identified with GC/TOFMS and LC/TOFMS together.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663508&req=5

f2: Metabolic profiling of LoVo cells treated with 10 mM metformin for different time points.(A–D) The PCA score plots for all groups, Con 8 h vs Met 8 h, Con 24 h vs Met 24 h, and Con 48 h vs Met 48 h, respectively. (E) The heatmap for the intensity variations of the total 158 metabolites identified with GC/TOFMS and LC/TOFMS together.
Mentions: The metabolic profile was evaluated between control and metformin treated cells at three different time points using unsupervised statistics, PCA on the basis of 158 identified cellular metabolites from GC/TOFMS and LC/TOFMS. The PCA loading plots showed that the cell samples of con 8 h and con 24 h almost clustered together, but were clearly separated from those of con 48 h (Fig. 2A), suggesting the gradual alteration of cellular metabolites with culture time. A similar time-dependent metabolic alteration was also observed in metformin-treated cells (Fig. 2A), which was further characterized by individual comparisons between control and metformin groups at different time points (Fig. 2B–D). To further investigate the impacts of both culture time and metformin treatment, a heatmap among all groups was drawn on the basis of relative intensity of total 158 identified metabolites compared to con 8 h group. Generally, the amount of cellular metabolites was obviously downregulated with culture time either in control or metformin-treated cells. However, most metabolites in met 8 h group were upregulated in comparison with con 8 h, but were further depleted by metformin at 24 h and 48 h (Fig. 2E). These metabolic profiles indicate a time-dependent alteration in amounts of cellular metabolites resulted from culture time and/or metformin treatment.

Bottom Line: An obvious time-dependent metabolic alteration was observed from 8 to 48 h, prior to the reduction of cell viability.Meanwhile, the transcirptomic profile revealed 134 and 3061 differentially expressed genes at 8 and 24 h by metformin.Altogether, our current data indicate that metformin suppressed the proliferation of LoVo cells, which may be due to the modulation on cell energy metabolism at both metabolic and transcriptional levels in a time-dependent way.

View Article: PubMed Central - PubMed

Affiliation: Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

ABSTRACT
Metformin is a widely used anti-diabetic drug with potential anti-tumor activity. However, little is known about its global metabolic and transcriptional impacts on tumor cells. In current study, we performed a metabolic profiling on human-derived colon cancer LoVo cells treated by 10 mM metformin for 8, 24 and 48 h. An obvious time-dependent metabolic alteration was observed from 8 to 48 h, prior to the reduction of cell viability. A total of 47, 45 and 66 differential metabolites were identified between control and metformin-treated cells at three time points. Most of the metabolites were up-regulated at 8 h, but down-regulated at 24 and 48 h by metformin. These metabolites were mainly involved in carbohydrates, lipids, amino acids, vitamins and nucleotides metabolism pathways. Meanwhile, the transcirptomic profile revealed 134 and 3061 differentially expressed genes at 8 and 24 h by metformin. In addition to the cancer signaling pathways, expression of genes involved in cell energy metabolism pathways was significantly altered, which were further validated with genes in glucose metabolism pathway. Altogether, our current data indicate that metformin suppressed the proliferation of LoVo cells, which may be due to the modulation on cell energy metabolism at both metabolic and transcriptional levels in a time-dependent way.

No MeSH data available.


Related in: MedlinePlus