OBJECTIVE: Although the chemotherapy drug hydroxyurea (HU) and the antiprogesterone mifepristone (RU486) have been used to treat meningiomas for which surgical and radiation therapies have failed, results have been disappointing. The addition of calcium channel antagonists (CCAs) to chemotherapeutic drugs enhances tumor growth inhibition in other tumor types, and the authors demonstrated that CCAs can block meningioma growth in vitro and in vivo. The purpose of this study was to test the effects of the addition of a CCA to HU or RU486 on meningioma growth. METHODS: Primary and malignant (IOMM-Lee) meningioma cell lines were treated with HU, RU486, or either of these plus diltiazem or verapamil. Assays for cell growth, apoptosis, and fluorescent-activated cell sorting were performed on in vitro cultures. Similar cell lines were implanted into nude mice and were treated with HU or RU486, in combination with a CCA. Tumors were analyzed by light microscopy, MIB-1, and factor VIII immunohistochemical staining studies. RESULTS: The addition of diltiazem or verapamil to HU or RU486 augmented meningioma growth inhibition by 20 to 60% in vitro. In vivo, tumors treated with combination drugs were smaller; and immunohistochemical analysis of the IOMM-Lee tumors showed a 10% decrease in the MIB-1 ratio (from 0.41 to 0.30) and an approximate 75% decrease in microvascular density. CONCLUSION: The addition of diltiazem or verapamil to HU or RU486 augments meningioma growth inhibition in vitro by inducing apoptosis and G1 cell-cycle arrest. The combination of HU and diltiazem inhibited the growth of meningiomas in vivo by decreasing proliferation and microvascular density. These results suggest a possible role for these drugs as an additional adjuvant therapy for recurrent or unresectable meningiomas.
OBJECTIVE: Although the chemotherapy drug hydroxyurea (HU) and the antiprogesterone mifepristone (RU486) have been used to treat meningiomas for which surgical and radiation therapies have failed, results have been disappointing. The addition of calcium channel antagonists (CCAs) to chemotherapeutic drugs enhances tumor growth inhibition in other tumor types, and the authors demonstrated that CCAs can block meningioma growth in vitro and in vivo. The purpose of this study was to test the effects of the addition of a CCA to HU or RU486 on meningioma growth. METHODS: Primary and malignant (IOMM-Lee) meningioma cell lines were treated with HU, RU486, or either of these plus diltiazem or verapamil. Assays for cell growth, apoptosis, and fluorescent-activated cell sorting were performed on in vitro cultures. Similar cell lines were implanted into nude mice and were treated with HU or RU486, in combination with a CCA. Tumors were analyzed by light microscopy, MIB-1, and factor VIII immunohistochemical staining studies. RESULTS: The addition of diltiazem or verapamil to HU or RU486 augmented meningioma growth inhibition by 20 to 60% in vitro. In vivo, tumors treated with combination drugs were smaller; and immunohistochemical analysis of the IOMM-Lee tumors showed a 10% decrease in the MIB-1 ratio (from 0.41 to 0.30) and an approximate 75% decrease in microvascular density. CONCLUSION: The addition of diltiazem or verapamil to HU or RU486 augments meningioma growth inhibition in vitro by inducing apoptosis and G1 cell-cycle arrest. The combination of HU and diltiazem inhibited the growth of meningiomas in vivo by decreasing proliferation and microvascular density. These results suggest a possible role for these drugs as an additional adjuvant therapy for recurrent or unresectable meningiomas.
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Authors: Hisham F Bahmad; Darine Daher; Abed A Aljamal; Mohamad K Elajami; Kei Shing Oh; Juan Carlos Alvarez Moreno; Ruben Delgado; Richard Suarez; Ana Zaldivar; Roshanak Azimi; Amilcar Castellano; Robert Sackstein; Robert J Poppiti Journal: J Histochem Cytochem Date: 2021-06-24 Impact factor: 2.479
Authors: Emily J Tonogai; Shan Huang; Rachel C Botham; Matthew R Berry; Stephen K Joslyn; Gregory B Daniel; Zixin Chen; Jianghong Rao; Xiang Zhang; Falguni Basuli; John H Rossmeisl; Gregory J Riggins; Amy K LeBlanc; Timothy M Fan; Paul J Hergenrother Journal: Neuro Oncol Date: 2021-10-01 Impact factor: 13.029
Authors: Alfonso Dueñas-González; Patricia García-López; Luis Alonso Herrera; Jose Luis Medina-Franco; Aurora González-Fierro; Myrna Candelaria Journal: Mol Cancer Date: 2008-10-23 Impact factor: 27.401
Authors: Wendy J Ingram; Lisa M Crowther; Erica B Little; Ruth Freeman; Ivon Harliwong; Desi Veleva; Timothy E Hassall; Marc Remke; Michael D Taylor; Andrew R Hallahan Journal: Exp Hematol Oncol Date: 2013-10-04