Tahereh Jalali Varnamkhasti1, Meisam Jafarzadeh1, Majid Sadeghizadeh2, Mahdi Aghili3. 1. Department of Molecular Genetics, School of Biological Sciences, Tarbiat Modares University, P.O. Box 14115-154, Tehran, Iran. 2. Department of Molecular Genetics, School of Biological Sciences, Tarbiat Modares University, P.O. Box 14115-154, Tehran, Iran. sadeghma@modares.ac.ir. 3. Radiation Oncology Research Center, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, P.O. Box 13145-158, Tehran, Iran. aghili@sina.tums.ac.ir.
Abstract
BACKGROUND: Curcumin was found to possess numerous pharmacological activities in clinical research, however, its biological effects together with radiation are yet to be addressed. The present study investigated whether the combined treatment of dendrosomal nanoformulation of curcumin (DNC) and gamma radiation can enhance the radiosensitivity of U87MG and MDA-MB-231 cell lines. METHODS: U87MG and MDA-MB-231 cell lines were exposed to 2 Gray (Gy) and 10 μM DNC determined by MTT assay, then subjected to clonogenic assay, cell cycle assay, and flow cytometric apoptosis analysis. Acridine Orange/Ethidium Bromide (AO/EB) and 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) stained cells were used to study morphologic changes. The expression evaluation of putative cell cycle genes, i.e., P53, P21, CCND1, and CCNB1 was carried out by RT-qPCR. RESULTS: Our findings indicated that the combined treatment with DNC and radiation might cooperatively augment the efficacy of ionizing radiation in the cancer cells and notably decrease the survival and viability of the cells in a time- and concentration-dependent manner. In addition to a synergistic effect deducted by sensitizer enhancement ratio (SER) assessment, co-treatment resulted in greater apoptotic cells than the individual treatments. Further experiments then indicated that DNC could effectively induce G2/M phase cell cycle arrest and apoptosis following irradiation. Conformably, there was a decrement of CCND1 and CCNB1 expression, and an increment of P53, P21 expression. CONCLUSIONS: The data implied that DNC as a radiosensitizer can enhance the lethal effect of ionizing radiation on cancer cells which could be a promising adjuvant therapy in clinical treatments.
BACKGROUND: Curcumin was found to possess numerous pharmacological activities in clinical research, however, its biological effects together with radiation are yet to be addressed. The present study investigated whether the combined treatment of dendrosomal nanoformulation of curcumin (DNC) and gamma radiation can enhance the radiosensitivity of U87MG and MDA-MB-231 cell lines. METHODS: U87MG and MDA-MB-231 cell lines were exposed to 2 Gray (Gy) and 10 μM DNC determined by MTT assay, then subjected to clonogenic assay, cell cycle assay, and flow cytometric apoptosis analysis. Acridine Orange/Ethidium Bromide (AO/EB) and 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) stained cells were used to study morphologic changes. The expression evaluation of putative cell cycle genes, i.e., P53, P21, CCND1, and CCNB1 was carried out by RT-qPCR. RESULTS: Our findings indicated that the combined treatment with DNC and radiation might cooperatively augment the efficacy of ionizing radiation in the cancer cells and notably decrease the survival and viability of the cells in a time- and concentration-dependent manner. In addition to a synergistic effect deducted by sensitizer enhancement ratio (SER) assessment, co-treatment resulted in greater apoptotic cells than the individual treatments. Further experiments then indicated that DNC could effectively induce G2/M phase cell cycle arrest and apoptosis following irradiation. Conformably, there was a decrement of CCND1 and CCNB1 expression, and an increment of P53, P21 expression. CONCLUSIONS: The data implied that DNC as a radiosensitizer can enhance the lethal effect of ionizing radiation on cancer cells which could be a promising adjuvant therapy in clinical treatments.
Authors: Paul D Brown; Manmeet S Ahluwalia; Osaama H Khan; Anthony L Asher; Jeffrey S Wefel; Vinai Gondi Journal: J Clin Oncol Date: 2017-12-22 Impact factor: 44.544
Authors: Laurence H Pearl; Amanda C Schierz; Simon E Ward; Bissan Al-Lazikani; Frances M G Pearl Journal: Nat Rev Cancer Date: 2015-03 Impact factor: 60.716