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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

The heatmaps for altered expression of genes involved in energy metabolism pathways among all groups.
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f4: The heatmaps for altered expression of genes involved in energy metabolism pathways among all groups.

Mentions: Metformin is a classical anti-diabetes drug by activating AMPK and its subsequent signaling pathways leading to the rebalancing of cell energy metabolism. Altered cell energy metabolism is a hallmark for tumor cells. To examine the comprehensive impacts on tumor cell energy metabolism of metformin, genes, which are mainly involved in cell energy metabolism pathways, were compared among groups including carbohydrates, lipids, amino acids, nucleotides, and vitamins metabolism (Fig. 4). Even though the metabolic profile of Met 8 h was significantly different from Con 8 h, the gene expression panels of energy metabolism pathways were similar between Con 8 h and Met 8 h (Fig. 4). A large number of genes were upregulated with culture time in Con 24 h group, however, most of the genes were downregulated by 24 h metformin treatment, except for several significantly upregulated genes such as phosphoenolpyruvate carboxykinase 1 (PCK1), aldehyde dehydrogenase 1 family, member A3 (ALDH1A3) in carbohydrates metabolism; phospholipase D2 (PLD2), lipid phosphate phosphohydrolase 3 (PPAP2B), diacylglycerol kinase (DGKE), sialidase 1 (NEU1) and sphingosine-1-phosphate phosphatase 1 (SGPP1) in lipids metabolism; spermidine/spermine N1-acetyltransferase 1 (SAT1), histamine N-methyltransferase (HNMT), and AU RNA binding protein/enoyl-CoA hydratase (AUH) in amino acids metabolism; adenosine deaminase (ADA), and 5′, 3′-nucleotidase, cytosolic (NT5C) in nucleotides metabolism; alkaline phosphatase, placental-like 2 (ALPPL2), ferritin, heavy polypeptide 1 (FTH1), NFS1 cysteine desulfurase (NFS1), and gamma-glutamyl carboxylase (GGCX) in vitamins metabolism (Fig. 4).


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)

The heatmaps for altered expression of genes involved in energy metabolism pathways among all groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: The heatmaps for altered expression of genes involved in energy metabolism pathways among all groups.
Mentions: Metformin is a classical anti-diabetes drug by activating AMPK and its subsequent signaling pathways leading to the rebalancing of cell energy metabolism. Altered cell energy metabolism is a hallmark for tumor cells. To examine the comprehensive impacts on tumor cell energy metabolism of metformin, genes, which are mainly involved in cell energy metabolism pathways, were compared among groups including carbohydrates, lipids, amino acids, nucleotides, and vitamins metabolism (Fig. 4). Even though the metabolic profile of Met 8 h was significantly different from Con 8 h, the gene expression panels of energy metabolism pathways were similar between Con 8 h and Met 8 h (Fig. 4). A large number of genes were upregulated with culture time in Con 24 h group, however, most of the genes were downregulated by 24 h metformin treatment, except for several significantly upregulated genes such as phosphoenolpyruvate carboxykinase 1 (PCK1), aldehyde dehydrogenase 1 family, member A3 (ALDH1A3) in carbohydrates metabolism; phospholipase D2 (PLD2), lipid phosphate phosphohydrolase 3 (PPAP2B), diacylglycerol kinase (DGKE), sialidase 1 (NEU1) and sphingosine-1-phosphate phosphatase 1 (SGPP1) in lipids metabolism; spermidine/spermine N1-acetyltransferase 1 (SAT1), histamine N-methyltransferase (HNMT), and AU RNA binding protein/enoyl-CoA hydratase (AUH) in amino acids metabolism; adenosine deaminase (ADA), and 5′, 3′-nucleotidase, cytosolic (NT5C) in nucleotides metabolism; alkaline phosphatase, placental-like 2 (ALPPL2), ferritin, heavy polypeptide 1 (FTH1), NFS1 cysteine desulfurase (NFS1), and gamma-glutamyl carboxylase (GGCX) in vitamins metabolism (Fig. 4).

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