The antibiotic chloramphenicol may be an effective new agent for inhibiting the growth of multiple myeloma.

Faqing Tian,Juheng Li,Huiqing Li,Sihan Zhang,Yingcai Huang,Chunyan Wang,Meiqin Tang,Xiaohui Cheng,Delan Ji

doi:10.18632/oncotarget.10623

Faqing Tian, Juheng Li + Show 7 more

Open Access

https://doi.org/10.18632/oncotarget.10623

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Abstract

Chloramphenicol is an old antibiotic that also inhibits mammalian mitochondrial protein synthesis. Our studies demonstrated that chloramphenicol is highly cytotoxic to myeloma cells, acting in a dose- and time-dependent manner. Chloramphenicol sharply suppressed ATP levels in myeloma cells at concentrations ≥ 25 μg/mL. Colorimetric and clonogenic assays indicate that chloramphenicol inhibits growth of myeloma cell lines at concentrations ≥ 50 μg/mL, and inhibits primary myeloma cell growth at concentrations ≥ 25 μg/mL. Flow cytometry and Western blotting showed that chloramphenicol induces myeloma cell apoptosis at concentrations ≥ 50 μg/mL. Chloramphenicol increased levels of cytochrome c, cleaved caspase-9 and cleaved caspase-3, suggesting that myeloma cell apoptosis occurs through the mitochondria-mediated apoptosis pathway. It thus appears chloramphenicol is not only an old antibiotic, it is also a potential cytotoxic agent effective against myeloma cells. This suggests chloramphenicol may be an effective “new” drug for the treatment of myeloma.

Highlights

Multiple myeloma (MM) is a B-cell tumor characterized by clonal expansion of malignant plasma cells within the bone marrow [1, 2]
We suggest that the proliferation and energy metabolism of MM cells are probably at a higher level than in normal peripheral blood mononuclear cells (PBMCs)
To test whether chloramphenicol impacts mitochondrial energy metabolism in MM cells, tumor cells were cultured with different concentrations of chloramphenicol prior to measuring cellular ATP content

Summary

Introduction

Multiple myeloma (MM) is a B-cell tumor characterized by clonal expansion of malignant plasma cells within the bone marrow [1, 2]. The recent use of proteasome inhibitors and immunomodulatory drugs has improved response rates and overall survival, this tumor remains incurable for the vast majority of patients, so new treatments are urgently needed [3, 4]. Cellular metabolism is the most important characteristic of living cells. Both normal and tumor cells must produce enough energy to maintain life and support cell proliferation by diverting enough metabolic intermediates to biosynthetic pathways [5,6,7]. Perhaps targeting tumor cell metabolism to suppress ATP production could be an effective future therapy for MM [8]

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