Calmodulin antagonists induce cell cycle arrest and apoptosis in vitro and inhibit tumor growth in vivo in human multiple myeloma

What makes the battle between medicine and cancer so difficult is that cancer can come in so many different forms and each one has its own unique set of causes and properties. This makes it virtually impossible to find a ubiquitous solution to this prevalent disease and causes the persistence of some of them despite significant advances in cancer research. Multiple myeloma (MM) is a hematological malignancy characterized by the excess accumulation of plasma cells in the bone marrow and the production of monoclonal immunoglobulins or paraproteins. Despite the attempt to apply many known cancer treatment methods, such as alkylating agents, anthracyclines, and corticosteroids as well as intensive therapies, including autologous hematopoietic stem cell transplantation and the novel agents such as bortezomib, thalidomide, and lenalidomide, a cure for MM still eludes modern medicine. Some recent breakthroughs, though, have opened the door for new treatment methods that are in the process of being studied to understand their effectiveness. For example, Calmodulin (CaM) has been identified as a possible therapy since it is known to mediate the effects of cytoplasmic Ca²⁺ levels and because of its involvement in myriad biological processes such as cell progression and apoptosis regulation. CaM regulates apoptotic processes both positively and negatively by mediating elevated levels of Ca²⁺, which can promote cell growth or induce cell death.

To understand the implications of this on MM treatment, Yokokura et al. have taken a look at the effects of the naphthalenesulfonamide derivatives W-7 and W-13, selective and cell-permeable CaM antagonists, on proliferation, cell cycle progression, and apoptosis in human MM cell lines. Their results indicate that CaM might offer a novel therapy for human MM and offer hope that an effective treatment can be developed. To test the effectiveness of CaM on MM cells, Yokokura and his team had to observe several cell behaviors when they were put into contact with CaM antagonists. One of the ways they did that was to observe mitochondrial membrane potential using the JC-10™ indicator. This indicator is a big improvement over previous versions in that it does not precipitate in aqueous solutions under normal conditions. This helps maintain the integrity of the sample and can help improve the reliability of the results obtained. Along the same lines, JC-10™ has been streamlined to help minimize hands-on time, which also helps to maintain the sample for appropriate study.

The results ascertained from this study by Yokokura and his colleagues have profound implications for the field of cancer research and the search for a cure. By being able to identify specific compounds that induce cancer cell death, researchers are one step closer than ever to developing effective treatments. However, this progress is based on the results obtained in studies like this and the validity of these results comes from the quality of materials. The JC-10™ indicator has a better signal intensity and a higher signal to background ratio, which helps produce definite results that can be trusted and used for the advancement in the field of medicine.

References

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1. Yokokura S, Yurimoto S, Matsuoka A, Imataki O, Dobashi H, Bandoh S, Matsunaga T. Calmodulin antagonists induce cell cycle arrest and apoptosis in vitro and inhibit tumor growth in vivo in human multiple myeloma. BMC Cancer (2014), doi: 10.1186/1471-2407-14-882.