Bisphosphonates induce apoptosis in human myeloma cell lines: a novel anti-tumour activity

C M Shipman, Michael John Rogers, J F Apperley, R G Russell, P I Croucher

Research output: Contribution to journalArticle

380 Citations (Scopus)

Abstract

Bisphosphonates are in widespread use to prevent bone resorption in a number of metabolic and tumour-induced bone diseases including multiple myeloma. Recent reports suggest that bisphosphonate treatment may be associated with an increase in patient survival, raising the possibility that these compounds may have a direct effect on the tumour cells. We have investigated whether the bisphosphonates clodronate, pamidronate and YM175 can directly affect the human myeloma cell lines U266-B1, JJN-3 and HS-Sultan in vitro. The effect of bisphosphonate treatment on cell number and cell cycle progression was examined using flow cytometry. The ability of bisphosphonates to induce apoptosis in human myeloma cell lines was determined on the basis of changes in nuclear morphology and of DNA fragmentation. Pamidronate and the more potent bisphosphonate. YM175, significantly decreased cell number (P <0.001) in JJN-3 and HS-Sultan cells. YM175 also caused cells to arrest in the S-phase of the cell cycle in the JJN-3 cell line. Both pamidronate and YM175 also caused an increase in the proportion of cells with altered nuclear morphology (P <0.05) and fragmented DNA, characteristic of apoptosis, in both JJN-3 and HS-Sultan cells. In contrast, clodronate had little effect on cell number and did not cause apoptosis at the concentrations examined. These data raise the possibility that some bisphosphonates could have direct anti-tumour effects on human myeloma cells in vivo.
Original languageEnglish
Pages (from-to)665-72
Number of pages8
JournalBritish Journal of Haematology
Volume98
Issue number3
Publication statusPublished - 1 Sep 1997

Fingerprint

Diphosphonates
pamidronate
Apoptosis
Cell Line
Neoplasms
Clodronic Acid
Cell Count
Cell Cycle
Bone Diseases
DNA Fragmentation
Bone Resorption
Multiple Myeloma
S Phase
Flow Cytometry
Survival
cimadronate
DNA
Therapeutics
HS 3
Sultan

Keywords

  • Apoptosis
  • Clodronic Acid
  • DNA, Neoplasm
  • Diphosphonates
  • Humans
  • Multiple Myeloma
  • Tumor Cells, Cultured

Cite this

Shipman, C. M., Rogers, M. J., Apperley, J. F., Russell, R. G., & Croucher, P. I. (1997). Bisphosphonates induce apoptosis in human myeloma cell lines: a novel anti-tumour activity. British Journal of Haematology, 98(3), 665-72.

Bisphosphonates induce apoptosis in human myeloma cell lines: a novel anti-tumour activity. / Shipman, C M; Rogers, Michael John; Apperley, J F; Russell, R G; Croucher, P I.

In: British Journal of Haematology, Vol. 98, No. 3, 01.09.1997, p. 665-72.

Research output: Contribution to journalArticle

Shipman, CM, Rogers, MJ, Apperley, JF, Russell, RG & Croucher, PI 1997, 'Bisphosphonates induce apoptosis in human myeloma cell lines: a novel anti-tumour activity', British Journal of Haematology, vol. 98, no. 3, pp. 665-72.
Shipman CM, Rogers MJ, Apperley JF, Russell RG, Croucher PI. Bisphosphonates induce apoptosis in human myeloma cell lines: a novel anti-tumour activity. British Journal of Haematology. 1997 Sep 1;98(3):665-72.
Shipman, C M ; Rogers, Michael John ; Apperley, J F ; Russell, R G ; Croucher, P I. / Bisphosphonates induce apoptosis in human myeloma cell lines: a novel anti-tumour activity. In: British Journal of Haematology. 1997 ; Vol. 98, No. 3. pp. 665-72.
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AB - Bisphosphonates are in widespread use to prevent bone resorption in a number of metabolic and tumour-induced bone diseases including multiple myeloma. Recent reports suggest that bisphosphonate treatment may be associated with an increase in patient survival, raising the possibility that these compounds may have a direct effect on the tumour cells. We have investigated whether the bisphosphonates clodronate, pamidronate and YM175 can directly affect the human myeloma cell lines U266-B1, JJN-3 and HS-Sultan in vitro. The effect of bisphosphonate treatment on cell number and cell cycle progression was examined using flow cytometry. The ability of bisphosphonates to induce apoptosis in human myeloma cell lines was determined on the basis of changes in nuclear morphology and of DNA fragmentation. Pamidronate and the more potent bisphosphonate. YM175, significantly decreased cell number (P <0.001) in JJN-3 and HS-Sultan cells. YM175 also caused cells to arrest in the S-phase of the cell cycle in the JJN-3 cell line. Both pamidronate and YM175 also caused an increase in the proportion of cells with altered nuclear morphology (P <0.05) and fragmented DNA, characteristic of apoptosis, in both JJN-3 and HS-Sultan cells. In contrast, clodronate had little effect on cell number and did not cause apoptosis at the concentrations examined. These data raise the possibility that some bisphosphonates could have direct anti-tumour effects on human myeloma cells in vivo.

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