Enhanced anti-tumor activity and cytotoxic effect on cancer stem cell population of metformin-butyrate compared with metformin HCl in breast cancer

Lee, Kyung Min; Lee, Minju; Lee, Jiwoo; Kim, Sung Wuk; Moon, Hyeong‐Gon; Noh, Dong‐Young; Han, Wonshik

doi:10.18632/oncotarget.9522

Cited by 23 publications

(20 citation statements)

References 45 publications

(53 reference statements)

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“…This drug is characterized by a broad spectrum of pleiotropic effects and good tolerability by patients. It may inhibit the growth and proliferation of gynecological cancer cells, such as those in breast cancer [30], ovary cancer [31], and cervical cancer [32]. In the past decade, many epidemiological studies showed the association between metformin use and the reduced risk and improved survival of patients with several types of cancers, including gynecological cancers.…”

Section: Discussionmentioning

confidence: 99%

Metformin Use Is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis

Tang

Zhu

et al. 2017

BioMed Research International

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Studies have suggested that metformin can potentially decrease the incidence of cancer and improve survival outcomes. However, the association between metformin use and the incidence and survival of endometrial cancer (EC) remains controversial. So, a meta-analysis was performed. An electronic search was conducted using PubMed, EMBASE, and Web of Science. The outcome measures were relative risks (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs) comparing the EC incidence and survival in patients treated with and without metformin. Eleven studies involving 766,926 participants were included in this study. In the pooled analysis of five studies which evaluated the association of metformin use with the incidence of EC, we found that metformin use was associated with a 13% reduction in EC risk among patients with diabetes (RR = 0.87, 95% CI: 0.80–0.95; p = 0.006). In the pooled analysis of six retrospective cohort studies evaluating the effect of metformin on the survival of EC patients, we found that, relative to nonuse, metformin use significantly improved the survival of EC patients (HR = 0.63, 95% CI: 0.45–0.87; p = 0.006). This study showed that metformin use was significantly associated with a decreased incidence of EC in diabetes and a favorable survival outcome of EC patients.

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Section: Discussionmentioning

confidence: 99%

Metformin Use Is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis

Tang

Zhu

et al. 2017

BioMed Research International

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“…However, recent studies focus on exploring the multidirectional actions of metformin. Metformin has demonstrated anti‐tumour activity in numerous experimental, epidemiologic, observational, and clinical studies . Metformin activates AMPK, a crucial cell energetic sensor, in normal and cancer cells, and consequently inhibits mTOR pathway implicated for protein synthesis and cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…Metformin has demonstrated anti-tumour activity in numerous experimental, epidemiologic, observational, and clinical studies. [23][24][25] Metformin activates AMPK, a crucial cell energetic sensor, in normal and cancer cells, and consequently inhibits mTOR pathway implicated for protein synthesis and cell proliferation. Moreover, AMPK activation induces cell cycle arrest by decreasing cyclin D1 protein level and induces p53-dependent autophagy.…”

Section: Celecoxib Induced Secretion Of Gdf-15 From Mscs In Each Glmentioning

confidence: 99%

Effect of metformin and celecoxib on cytotoxicity and release of GDF‐15 from human mesenchymal stem cells in high glucose condition

Zafarvahedian

Roohi

Sepand

et al. 2017

Cell Biochemistry & Function

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Mesenchymal stem cells (MSCs) have therapeutic potential for treatment of diabetes. However, in vitro behavior of MSCs in high glucose condition as well as presence of glucose lowering agents is not fully understood. Because MSCs have an important role in tissue repair, we examined the effects of metformin and celecoxib on viability of MSCs in different glucose conditions. MSCs, from umbilical cord blood, were cultured in normoglycemic (glucose 5.5 mM), midglycemic (glucose 10 mM), and hyperglycemic (glucose 25 mM) conditions, and the cell viability was evaluated by MTT assay. The cytotoxicity and secretion of GDF-15 were further tested in MSCs treated with metformin and celecoxib in various glucose concentrations. Our results showed that high glucose condition lowered viability of MSCs. Metformin treatment also inhibited proliferation of MSCs, but its toxicity was not changed in high glucose condition. Celecoxib induced cytotoxicity in MSCs, and the toxicity was increased in high glucose condition. Metformin and celecoxib induced release from MSCs; however, high glucose inhibited the metformin-induced GDF-15 release. These findings suggested that metformin did not increase the cytotoxicity of high glucose condition in MSCs. Moreover, celecoxib treatment in diabetic condition can reduce the viability of MSCs to proliferate and regenerate perhaps via change in release of GDF-15.

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“…And furthermore, a majority of dysregulated gene products were involved in cytokinecytokine receptor interaction and AMPK signaling pathways. AMPK signaling pathway has been previously shown to inhibit mTOR and impair cell cycle progression at S and G2/M phases, playing a significant role in BCSC by Lee et al 39 Meanwhile, previous study also reported that there is a connection between BCSC and cytokinecytokine receptor interaction. 40 With regard to the GO and KEGG pathway analysis presented, the relationship between these biological processes and TNBC CSCs should be well studied in the future.…”

Section: T a B L E 4 Multivariate Cox Regressionmentioning

confidence: 96%

Identification of tRNA‐derived small noncoding RNAs as potential biomarkers for prediction of recurrence in triple‐negative breast cancer

Feng

Chu

et al. 2018

Cancer Medicine

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Triple‐negative breast cancer (TNBC), an intrinsic subtype of breast cancer, is characterized by aggressive pathology and shorter overall survival. Yet there is no effective therapy for these patients. Breast cancer stem cells (BCSCs) in TNBC may account for treatment failure. It is urgent to identify new therapeutic targets for TNBC. tRNA‐derived small noncoding RNAs (tDRs) represent a new class of small noncoding RNAs (sncRNA), which have been reported in some human diseases and biological processes. However, there is no detailed information about the relationship between tDRs and BCSCs. In this study, a population of CD44+/CD24−/low cells was isolated and identified by reliable BCSC surface markers. tDR expression profiles in TNBC and non‐TNBC CSCs were performed by RNA sequencing. A total of 1327 differentially expressed tDRs contained 18 upregulated and 54 downregulated in TNBC group. Furthermore, the selected tDRs were validated by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). tDR‐000620 expression level was consistently lower in TNBC cell lines CSCs (all P < 0.05) and serum samples (t = 2.597, P = 0.013). tDR‐000620 expression was significant association with age (P = 0.018), node status (P = 0.026) and local recurrence (P = 0.019) by chi‐square test. Kaplan‐Meier method with log‐rank test for comparison of recurrence curves. The results showed that the tDR‐000620 expression (P = 0.002) and node status (P = 0.001) group were statistically significant with recurrence‐free survival. Furthermore, multivariate Cox regression demonstrated that lymphatic metastasis (HR, 3.616; 95% CI, 1.234‐10.596; P = 0.019) and low tDR‐000620 expression (HR, 0.265; 95% CI, 0.073‐0.959; P = 0.043) were two independent adverse predictive factors for recurrence‐free survival. Finally, we found that tDR‐000620 participated in some important biological processes though GO and KEGG analysis. Taken together, our study reveals the expression profiles of tDRs in TNBC and non‐TNBC CSCs. It offers helpful information to understand the tDR‐000620 expression is responsible for the aggressive phenotype of BCSCs. It may provide predictive biomarkers and therapeutic targets for TNBC recurrence.

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Enhanced anti-tumor activity and cytotoxic effect on cancer stem cell population of metformin-butyrate compared with metformin HCl in breast cancer

Cited by 23 publications

References 45 publications

Metformin Use Is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis

Metformin Use Is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis

Effect of metformin and celecoxib on cytotoxicity and release of GDF‐15 from human mesenchymal stem cells in high glucose condition

Identification of tRNA‐derived small noncoding RNAs as potential biomarkers for prediction of recurrence in triple‐negative breast cancer

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