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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

Metformin suppressed the proliferation of LoVo cells dose- and time-dependently.(A) Human-derived colon cancer cells, LoVo cells were cultured in 10% FBS DMEM and treated with or without metformin at a series of concentrations from 0.5 to 10 mM for 48 h. Then, cell viability was assayed with CCK-8 according to its instruction. (B) LoVo cells were treated with metformin for 8, 24 and 48 h at the concentrations of 1 and 10 mM, respectively. The cell number was evaluated with CCK-8. (C) The representative photograph of cell culture media treated with either 1 or 10 mM metformin for different time points. *P < 0.05, **P < 0.01 compared to corresponding control cells. Data are means ± S.E of at least two independent experiments with five replications for each group.
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f1: Metformin suppressed the proliferation of LoVo cells dose- and time-dependently.(A) Human-derived colon cancer cells, LoVo cells were cultured in 10% FBS DMEM and treated with or without metformin at a series of concentrations from 0.5 to 10 mM for 48 h. Then, cell viability was assayed with CCK-8 according to its instruction. (B) LoVo cells were treated with metformin for 8, 24 and 48 h at the concentrations of 1 and 10 mM, respectively. The cell number was evaluated with CCK-8. (C) The representative photograph of cell culture media treated with either 1 or 10 mM metformin for different time points. *P < 0.05, **P < 0.01 compared to corresponding control cells. Data are means ± S.E of at least two independent experiments with five replications for each group.

Mentions: To determine an optimal concentration of metformin for suppressing proliferation of LoVo cells, we first treated LoVo cells with a series of concentrations of metformin from 0.5 to 10 mM for 48 h, and found that the proliferation of LoVo cells were significantly suppressed by metformin in a dose-dependent way (Fig. 1A). Then, we treated the LoVo cells with 1 mM and 10 mM metformin, respectively, and the cell viability was measured at 8, 24, and 48 h of treatment to characterize the time-dependent impacts of metformin. We observed that the proliferation of LoVo cells were significantly suppressed by metformin after 24 h treatment at both 1 and 10 mM concentrations, whereas there was no significant difference in cell viability among groups at 8 h (Fig. 1B). Meanwhile, the color of cell cultural media underwent obvious change in metformin treated wells at 24 and 48 h (Fig. 1B), which may due to the over-production of lactate induced by metformin.


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)

Metformin suppressed the proliferation of LoVo cells dose- and time-dependently.(A) Human-derived colon cancer cells, LoVo cells were cultured in 10% FBS DMEM and treated with or without metformin at a series of concentrations from 0.5 to 10 mM for 48 h. Then, cell viability was assayed with CCK-8 according to its instruction. (B) LoVo cells were treated with metformin for 8, 24 and 48 h at the concentrations of 1 and 10 mM, respectively. The cell number was evaluated with CCK-8. (C) The representative photograph of cell culture media treated with either 1 or 10 mM metformin for different time points. *P < 0.05, **P < 0.01 compared to corresponding control cells. Data are means ± S.E of at least two independent experiments with five replications for each group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Metformin suppressed the proliferation of LoVo cells dose- and time-dependently.(A) Human-derived colon cancer cells, LoVo cells were cultured in 10% FBS DMEM and treated with or without metformin at a series of concentrations from 0.5 to 10 mM for 48 h. Then, cell viability was assayed with CCK-8 according to its instruction. (B) LoVo cells were treated with metformin for 8, 24 and 48 h at the concentrations of 1 and 10 mM, respectively. The cell number was evaluated with CCK-8. (C) The representative photograph of cell culture media treated with either 1 or 10 mM metformin for different time points. *P < 0.05, **P < 0.01 compared to corresponding control cells. Data are means ± S.E of at least two independent experiments with five replications for each group.
Mentions: To determine an optimal concentration of metformin for suppressing proliferation of LoVo cells, we first treated LoVo cells with a series of concentrations of metformin from 0.5 to 10 mM for 48 h, and found that the proliferation of LoVo cells were significantly suppressed by metformin in a dose-dependent way (Fig. 1A). Then, we treated the LoVo cells with 1 mM and 10 mM metformin, respectively, and the cell viability was measured at 8, 24, and 48 h of treatment to characterize the time-dependent impacts of metformin. We observed that the proliferation of LoVo cells were significantly suppressed by metformin after 24 h treatment at both 1 and 10 mM concentrations, whereas there was no significant difference in cell viability among groups at 8 h (Fig. 1B). Meanwhile, the color of cell cultural media underwent obvious change in metformin treated wells at 24 and 48 h (Fig. 1B), which may due to the over-production of lactate induced by metformin.

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