In vitro comparison of the cytotoxic effects of statins on U266 myeloma cell line

Abstract

Background & objectives: Statins are one of the most widely used drugs and have antilipidemic effects as well as antioxidant, anti-inflammatory, anti-angiogenic and anti-tumorigenic effects. It has been shown that the synergistic combinations of statins which can provide better clinical benefit in the treatment of cancer and if administered with other anticancer agents, may be an alternative treatment modality. The aim of this study was to assess the efficacy of administrating statin in multiple myeloma (MM) cell line on cell proliferation. Methods: U266 myeloma cells were cultured in 25 or 75 cm2 flasks by using cell culture medium mixtures obtained with the supplementation of 10 per cent foetal bovine serum and one per cent of penicillin-streptomycin into RPMI 1640 medium. When the cells reached confluence (reached to the density of 70%), they were reproduced by passaging. Cytotoxicity was evaluated by using the XTT test. Results: Statins (atorvastatin and simvastatin), were administered to the U266 myeloma cell line at 100, 50, 25, 12.5, 6.25 and 3.12 μM concentrations. Inhibitor concentration 50 (IC50) values calculated for atorvastatin and simvastatin were determined as 94 and 38 μM, respectively. While 100, 50, 25, 12.5, 6.25 and 3.12 μM concentrations were used for bortezomib, the IC50 value calculated for this agent was 18.2 nM. When six concentrations of bortezomib used in the study were combined with 12.5 μM inactive concentrations of statins that did not cause inhibition in cell proliferation, both atorvastatin and simvastatin increased the effect of bortezomib at all the concentrations used, and simvastatin showed a stronger efficacy than atorvastatin. Interpretation & conclusions: Our in vitro results indicated that atorvastatin and simvastatin when used along with the conventional treatment in myeloma patients, may improve the effectiveness of the standard therapy and prevent the bortezomib-induced cytotoxic and neurotoxic side effects when used at a low dose. Further studies need to be done in MM patints to confirm these findings.

Cholesterol Metabolic Reprogramming in Cancer and Its Pharmacological Modulation as Therapeutic Strategy

“…In vivo studies evidenced that statins reduce tumor growth and arrest metastasis progression ( 113 , 182 – 186 ). Terzi and co-workers ( 187 ) evaluated the effect of two statins, atorvastatin and simvastatin, combined with the standard chemotherapeutic agent, bortezomib, in human multiple myeloma. The results showed that statins are able to improve the effectiveness of bortezomib and reduce the adverse effects ( 187 ).…”

“…Terzi and co-workers ( 187 ) evaluated the effect of two statins, atorvastatin and simvastatin, combined with the standard chemotherapeutic agent, bortezomib, in human multiple myeloma. The results showed that statins are able to improve the effectiveness of bortezomib and reduce the adverse effects ( 187 ). The combined treatment of pivastatin with gemcitabine synergically reduced cell proliferation of MIA PaCa-2 cells inducing cell cycle arrest.…”

The mevalonate pathway is an actionable vulnerability of t(4;14)-positive multiple myeloma

“…To date, few studies have evaluated statins in combination with bortezomib in MM [14,53]. Notably, our study is the first to describe a molecular subtype of MM in which these two drugs interact synergistically, at physiologically relevant concentrations.…”

Hypocholesterolemia and Statins in Multiple Myeloma

“…Myeloma cells were reported to need cholesterol for growth and proliferation in mouse cell lines. In addition, drugs such as simvastatin, atorvastatin, and lovastatin were shown to cause the death of MM cell lines [4,5]. Failure to fully evaluate microenvironment effects was one of the limitations of these studies.…”