Lidamycin shows highly potent cytotoxic to myeloma cells and inhibits tumor growth in mice.

Abstract

AIM:

To investigate the effects of lidamycin (LDM) on a mouse myeloma cell line (SP2/0) and human multiple myeloma cell lines (U266 and SKO-007), and provide the basis for the use of LDM in cancer therapy.

METHODS:

A 3-[4,5-dimethylthiazol-2-yl]5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]2H-tetrazolium inner salt (MTS) assay was used to determine the degree of growth inhibition by the drugs analyzed in this study. Cell cycle distribution and analysis were measured by flow cytometry combined with propidium iodide (PI) staining. The effects on apoptosis were measured by Hoechst 33342 staining and by flow cytometry combined with fluorescein-isothiocyanate-Annexin V/propidium iodide (FITC-Annexin V/PI) staining. Protein expression was determined by Western blot analysis. In vivo antitumor activity was measured using a murine myeloma model in BALB/c mice.

RESULTS:

There was a significant reduction in cell proliferation after treatment with LDM. The overall growth inhibition correlated with increased apoptotic cell death. LDM-induced cell apoptosis was associated with the activation of c-Jun-N-terminal kinase (JNK), and cleavage of caspase-3/7 and poly (ADP-ribose) polymerase (PARP). LDM markedly suppressed tumor growth in a murine myeloma model.

CONCLUSION:

LDM induces apoptosis in murine myeloma SP2/0 cells as well as in human myeloma U266 and SKO-007 cell lines. The sustained activation of JNK might play a critical role in LDM-induced apoptosis in the SP2/0 cell line. LDM demonstrates significant antitumor efficacy against myeloma SP2/0 cells in mice. Taken together, our data provide some clues for further research of the effects of LDM on human multiple myeloma.Acta Pharmacologica Sinica (2009) 30: 1025-1032; doi: 10.1038/aps.2009.75.

• Authors: Yong-Zhan Zhen, Ya-Jun Lin, Yi Li, Yong-Su Zhen
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 30 Issue 7 Pg. 1025-32 (Jul 2009) ISSN: 1745-7254 [Electronic] United States
• PMID: 19575006 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminoglycosides
• Antibiotics, Antineoplastic
• Enediynes
• C 1027
• JNK Mitogen-Activated Protein Kinases

Topics

• Aminoglycosides (pharmacology, therapeutic use)
• Animals
• Antibiotics, Antineoplastic (pharmacology, therapeutic use)
• Apoptosis (physiology)
• Cell Line, Tumor (drug effects)
• Cell Proliferation (drug effects)
• Enediynes (pharmacology, therapeutic use)
• Enzyme Activation
• Female
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Mice
• Mice, Inbred BALB C
• Multiple Myeloma (drug therapy, pathology)
• Neoplasm Transplantation
• Random Allocation