BACKGROUND: Accumulating reports indicate that statins widely prescribed for hypercholesteromia have antineoplastic activity. We hypothesized that because statins inhibit farnesylation of Ras that is often mutated in multiple myeloma (MM), as well as the production of interleukin (IL)-6, a key cytokine in MM, they may have antiproliferative and/or proapoptotic effects in this malignancy. METHODS: U266, RPMI 8226, and ARH77 were treated with simvastatin (0-30 microM) for 5 days. The following aspects were evaluated: viability (IC50), cell cycle, cell death, cytoplasmic calcium ion levels, supernatant IL-6 levels, and tyrosine kinase activity. RESULTS: Exposure of all cell lines to simvastatin resulted in reduced viability with IC50s of 4.5 microM for ARH77, 8 microM for RPMI 8226, and 13 microM for U266. The decreased viability is attributed to cell-cycle arrest (U266, G1; RPMI 8226, G2M) and cell death. ARH77 underwent apoptosis, whereas U266 and RPMI 8226 displayed a more necrotic form of death. Cytoplasmic calcium levels decreased significantly in all treated cell lines. IL-6 secretion from U266 cells was abrogated on treatment with simvastatin, whereas total tyrosine phosphorylation was unaffected. CONCLUSIONS: Simvastatin displays significant antimyeloma activity in vitro. Further research is warranted for elucidation of the modulated molecular pathways and clinical relevance.
BACKGROUND: Accumulating reports indicate that statins widely prescribed for hypercholesteromia have antineoplastic activity. We hypothesized that because statins inhibit farnesylation of Ras that is often mutated in multiple myeloma (MM), as well as the production of interleukin (IL)-6, a key cytokine in MM, they may have antiproliferative and/or proapoptotic effects in this malignancy. METHODS: U266, RPMI 8226, and ARH77 were treated with simvastatin (0-30 microM) for 5 days. The following aspects were evaluated: viability (IC50), cell cycle, cell death, cytoplasmic calcium ion levels, supernatant IL-6 levels, and tyrosine kinase activity. RESULTS: Exposure of all cell lines to simvastatin resulted in reduced viability with IC50s of 4.5 microM for ARH77, 8 microM for RPMI 8226, and 13 microM for U266. The decreased viability is attributed to cell-cycle arrest (U266, G1; RPMI 8226, G2M) and cell death. ARH77 underwent apoptosis, whereas U266 and RPMI 8226 displayed a more necrotic form of death. Cytoplasmic calcium levels decreased significantly in all treated cell lines. IL-6 secretion from U266 cells was abrogated on treatment with simvastatin, whereas total tyrosine phosphorylation was unaffected. CONCLUSIONS:Simvastatin displays significant antimyeloma activity in vitro. Further research is warranted for elucidation of the modulated molecular pathways and clinical relevance.
Authors: Mara M Epstein; George Divine; Chun R Chao; Karen E Wells; Heather Spencer Feigelson; Delia Scholes; Douglas Roblin; Marianne Ulcickas Yood; Lawrence S Engel; Andrew Taylor; Joan Fortuny; Laurel A Habel; Christine C Johnson Journal: Int J Cancer Date: 2017-05-15 Impact factor: 7.396
Authors: Danitza Pradelli; Davide Soranna; Antonella Zambon; Alberico Catapano; Giuseppe Mancia; Carlo La Vecchia; Giovanni Corrao Journal: Cancer Med Date: 2015-03-21 Impact factor: 4.452
Authors: María Elena Crescencio; Emma Rodríguez; Araceli Páez; Felipe A Masso; Luis F Montaño; Rebeca López-Marure Journal: Int J Biomed Sci Date: 2009-12