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Table 3 Summary of in vitro studies reporting effects of bisphosphonate on macrophages

From: Tumour macrophages as potential targets of bisphosphonates

Cell Type

Bisphosphonate

Main Findings

Reference

J774 cells

RAW 264 cells

PAM, ALN, IBA, 100 μM

24 hours

Inhibited macrophage proliferation.

Reduced cell viability. Increased cell death.

Rogers et al [68]

J774 cells

ALN, 25 μM or 100 μM

IBA 5 μM, 7.5 μM or 10 μM

24 hours

Dose dependent increase in accumulation of unprenylated Rap1A.

Firth et al [97]

RAW 264 cells

ALN 10 μM; 5, 7, 9 or 16 hours

ALN 100 μM; 1, 3, 5, 7, 9, 16 hours.

Dose and time dependent increase in accumulation of unprenylated Rap1A. Detectable after 16 hours incubation with 10 μM or 5 hours incubation with 100 μM

Monkkonen et al [98]

J774 A.1 cells

PAM, ZOL, ALN, RIS

1-100 μM for 72 hours.

All BPs induced significant apoptosis

ZOL > RIS > ALN > PAM.

Moreau et al [49]

Macrophage precursor from bone marrow cells and bone marrow derived macrophages

PAM

2.5 × 10-7M (=0.25 μM), 96 hours

Significant inhibition M-CSF induced proliferation of bone marrow precursors

Cecchini et al [69]

Activated human monocyte/macrophage

PAM

100-300 μM

24 hour pre-treatment Then activated with LPS.

Dose-dependent inhibition of MMP-9 expression

Lower doses PAM increases expression.

Valleala et al [71]

Human macrophage-like cell line U937

Clodrolip

20-200 μM

2 days

Decreased cell survival

Hiraoka et al [85]

Murine Macrophages

Clodrolip

9 μg per well

29 hours

Decreased cell viability

Gazzangia et al [86]

Murine peritoneal macrophages

Clodrolip

1 mg/ml

6 hours.

Dose-dependent increase in apoptosis.

Zeisberger et al [87]

Bone marrow cells from naive mice cultured with M-CSF or tumour supernatant.

Zoledronic acid

0.03, 0.15, 0.3 μM

6 days

Dose-dependent inhibition in differentiation of myeloid cells to macrophages.

Decreased in M2 phenotype compared to control.

Veltman et al [89]