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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

Transcriptomic profiling of LoVo cells treated with 10 mM metformin for 8 and 24 hours.(A) The PCA score plot of all analyzed transcripts of all 4 groups. (B) The summary of all up- and down-regulated genes by metformin treatment. (C) The number of altered genes by metformin treatment for either 8 or 24 h. (D,E) The GO enrichment analysis of altered genes by metformin treatment for either 8 or 24 h.
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f3: Transcriptomic profiling of LoVo cells treated with 10 mM metformin for 8 and 24 hours.(A) The PCA score plot of all analyzed transcripts of all 4 groups. (B) The summary of all up- and down-regulated genes by metformin treatment. (C) The number of altered genes by metformin treatment for either 8 or 24 h. (D,E) The GO enrichment analysis of altered genes by metformin treatment for either 8 or 24 h.

Mentions: In addition to the metabolic profiling, the global gene expression of control and metformin-treated cells at 8 and 24 h was also analyzed for elucidating the transcriptional modulation of metformin. First, the transcriptomic profiling with all the detected probes was evaluated using PCA model. The PCA score plot showed that samples of control or metformin-treated cells at 8 h were relatively clustered together, whereas those at 24 h were distinctly separated, suggesting the time-related gene expression panel of control cells. Meanwhile, 24 h metformin treatment resulted in obvious separation with samples of con 24 h, which is consistent with their metabolic profiles (Fig. 3A). There were 134 (67 up-regulation and 67 down-regulation) and 3061 (983 up-regulation and 2078 down-regulation) differentially expressed genes between control and metformin-treated cells at 8 and 24 h, respectively (Fig. 3B). Most of the genes were uniquely regulated at the two time points, in which 64 genes were commonly modulated at both time points (Fig. 3C).


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)

Transcriptomic profiling of LoVo cells treated with 10 mM metformin for 8 and 24 hours.(A) The PCA score plot of all analyzed transcripts of all 4 groups. (B) The summary of all up- and down-regulated genes by metformin treatment. (C) The number of altered genes by metformin treatment for either 8 or 24 h. (D,E) The GO enrichment analysis of altered genes by metformin treatment for either 8 or 24 h.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Transcriptomic profiling of LoVo cells treated with 10 mM metformin for 8 and 24 hours.(A) The PCA score plot of all analyzed transcripts of all 4 groups. (B) The summary of all up- and down-regulated genes by metformin treatment. (C) The number of altered genes by metformin treatment for either 8 or 24 h. (D,E) The GO enrichment analysis of altered genes by metformin treatment for either 8 or 24 h.
Mentions: In addition to the metabolic profiling, the global gene expression of control and metformin-treated cells at 8 and 24 h was also analyzed for elucidating the transcriptional modulation of metformin. First, the transcriptomic profiling with all the detected probes was evaluated using PCA model. The PCA score plot showed that samples of control or metformin-treated cells at 8 h were relatively clustered together, whereas those at 24 h were distinctly separated, suggesting the time-related gene expression panel of control cells. Meanwhile, 24 h metformin treatment resulted in obvious separation with samples of con 24 h, which is consistent with their metabolic profiles (Fig. 3A). There were 134 (67 up-regulation and 67 down-regulation) and 3061 (983 up-regulation and 2078 down-regulation) differentially expressed genes between control and metformin-treated cells at 8 and 24 h, respectively (Fig. 3B). Most of the genes were uniquely regulated at the two time points, in which 64 genes were commonly modulated at both time points (Fig. 3C).

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