Table 1.
In vitro Effect of Metformin Treatment of Human Breast Cancer Cell Lines
| Authors (reference) | Cell line | [Metformin] | Cell proliferation (method used) | Other Measurements |
|---|---|---|---|---|
|
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| Zakikhani et al (22) | MCF-7 MCF-10A |
0–20 mM | by 80% dose dependent (Alamar Blue) | Only MCF-7 used pAMPK ↑ mTor ↓ pS6 ↓ p70S6K ↓ |
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| Dowling et al (31) | MCF-7 | 0–20mMol/L | pAMPK ↑ 35S-methionine protein synthesis reduced and maintained |
|
| MDA-MB-231 | 0–20mMol/L | pAMPK no effect 35S-methionine protein synthesis no effect |
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|
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| Zhuang & Miskimins (23) | MCF-7 | 0–12mM | ↓ (dose dependent) 1 day | |
| MCF-7 | 8mM | ↓ 50% 3 days |
pAMPK ↑ Apoptosis ↑↑↑ Cyclin D1 ↓ |
|
| MDA-MB-231 | 8mM | No effect 3 days |
WTp27 transfected ↓ cell proliferation | |
| BT20 | 8mM | ↓ 50% 3 days |
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| T47D | 8mM | ↓ 80% 3 days |
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| MDA-MB-453 | 8mM | ↓ 50% 3 days (cell count) |
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| Liu et al (27) | MCF-7 MDA-MB453 BT474 SKR3 MDA-MB-468 BT20 MDA-MB-231 BT549 |
0–40 mM | ↓ Dose dependent for triple negative lines MDA-MB-468 BT20 MDA-MB-231 BT549 (MTS) |
Apoptosis ↑ also for triple negative lines in response to 30 mM metformin |
|
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| Alimova et al (26) | MCF-7 MCF-7/713 BT-474 SKBR3 |
0–50 mM | ↓ Dose dependent (MTS) | Reduced colony formation Inhibited MAPK, Akt, mTOR all cell lines Reduced erbB2 in cells overexpressing Did not affect apoptosis |
|
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| Vasquez-Martin et al (24) | MCF-7 SKBR3 MCF-7/pBABE/HER2 MCF-7/HER2 |
0–10 mM | ↓ Dose dependent Greater response in HER2 lines (MTT) |
pAMPK ↑ p70S6K1 ↓ MCF-7/pBABE/HER2 and MCF-7/HER2 lines created to express HER2 |
|
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| Zakikhani et al (21) | MCF-7 T47D HS578T MDA-MB-231 |
0–20 mM | ↓ Dose dependent (Alamar Blue) | |
|
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| Jung et al (79) | MCF-7 | 0–10 mM | ↓ Dose dependent 1 and 10 mM significant (MTT) | Mammosphere formation ↓ by metformin (1 & 10 mM) vs 0 in presence of E2 or BPA or dioxin Metformin acting through OCT4 and stem cells |
|
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| Zhu et al (25) | BT-20 BT-549 MCF-7 MDA-MB-231 MDA-MB-453 MDA-MB-468 SK-BR-3 |
0–20 mM At 1, 2 and 3 days |
↓ decreasing proliferation with ↑ metformin concentration except for SK- BR-3 day 1 (dye based) | Different degrees of inhibition of proliferation but no pattern in relation to cell type |
|
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| Liu et al (80) | BT-474 BT-474 R SK-BR-3 SK-BR-3 R |
0–10 mmol/L | ↓ growth > response to metformin in R cells (MTS) | R cell lines resistant to Herceptin |
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| Cufi et al (81) | JIMT-1 parent JIMT-1-CDlow JIMT-1- non-CDlow |
0–10 Mmol/L | JIMT-1-CDlow most sensitive to metformin at all concentrations (MTT) | Cell line resistant to Herceptin CDlow breast cancer initiating Metformin affecting CSC = stem cells See also in vivo xenograft study |
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| Williams et al (28) | MDA-MB-468 | 0.04–1 mM 48 h (then w/o for 5 days) (dye based) |
1 mM dose reduced proliferation | Apoptosis induced at 5–20 mM but not 1 mM Cell senescence induced by 1 mM Gene expression induced for metabolic stress response and proliferative arrest |
|
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| Zhu et al (30) | BT-474 SKBR-3 78617 (mouse MMTV-ErbB2) MCF10A |
0–20 mmol/L 6 days | 3 cancer lines dose dependent ↓ growth MCF10A also response but not as great (SRB assay) | pAMPK at 1 and 5 dose for SKBR-3 and BT-474 Low dose metformin (0.1 & 1) ↓ sphere formation |
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| Du et al (29) | T47D | 0–16 mM | ↓ Dose dependent (dye based) | Metformin at 4 mM induced cell cycle arrest and pAMPK ↑ |