BioMed Research International / 2014 / Article / Tab 1

Review Article

Metformin against Cancer Stem Cells through the Modulation of Energy Metabolism: Special Considerations on Ovarian Cancer

Table 1

Preclinical studies of metformin targeting metabolism of ovarian cancer cells and/or ovarian CSCs.

Agent or drug (dosage)CSCs enrichedAloneCombination with other drugsMechanism of actionReference

(0.02 mmol/L in vitro)
NoNo significant loss of viability or change in cell cycleImprovement of cytotoxic response to carboplatin< > [63]

(5 mmol/L in vitro),
(5 µmol/L in vitro)
NoInhibition of growth in vitroCombination with PEITC increases cell death in vitroROS generation [62]

(5 mmol/L in vitro)
NoInduced apoptosis in vitroCombination with cisplatin enhances apoptosisAMPK-independent, downregulating Bcl-2/Bcl-xL, upregulating Bax/Bad [65]

(100–200 mg/kg in vivo)
No Inhibition of ovarian tumor growth, proliferation, metastasis, and angiogenesis in vivoCombination with cisplatin reduces tumor growthAMPK/mTOR, antiangiogenic effect [64]

(5 mmol/L in vitro)
NoInhibition of proliferation in vitro< >Cell cycle arrest, AMPK/mTOR and AMPK independent pathway [66]

(5–50 mmol/L in vitro)
NoInhibition of proliferation in vitroImprovement of cytotoxic response to cisplatinAMPK/mTOR [67]

(0.3 mmol/L in vitro, 150 mg/kg in vivo)
ALDH+ cellsInhibition of ovarian CSC/TIC growth in vitro, nonsignificant decreases in tumor growth in vivoCombination with cisplatin restricts tumor growth in vivo< > [13]

CSC, cancer stem cell; ROS, reactive oxygen species; AMPK, adenosine monophosphate-activated protein kinase; mTOR, mammalian target of rapamycin; ALDH, aldehyde dehydrogenase; PEITC, phenethyl isothiocyanate; TIC, tumor initiating cell. Modified and adapted with permission from reference [15].

Article of the Year Award: Outstanding research contributions of 2020, as selected by our Chief Editors. Read the winning articles.