A study conducted at the Department of Physiology and Pharmacology, University of Cantabria, Spain, explores how melatonin enhances the sensitivity of human breast cancer cells to ionizing radiation. The research delves into the effects of melatonin on cell proliferation, interactions with ionizing radiation, and potential implications for cancer treatment strategies.
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DEPARTMENT OF PHYSIOLOGY AND PHARMACOLOGY UNIVERSITY OF CANTABRIA, SANTANDER, SPAIN MELATONIN SENSITIZES HUMAN BREAST CANCER CELLS TO IONIZING RADIATION Carolina Alonso-Gonz lez
IRRADIATION (dose ranging 4-12 Gy) Cell proliferation Cell cycle phase distribution RAD51 and DNA-PKcs mRNA gene expression Melatonin 1 mM Melatonin 10 M 7 Days Melatonin 1 nM Malignant epithelial cells MCF-7
EFFECTS OF MELATONIN ON BREAST CANCER CELL PROLIFERATION (MCF-7) 150 150 4 Days Cell proliferation 125 Cell proliferation 125 (% of control) (% of control) 100 100 a a 75 75 a b c 10 M 50 50 1 mM 1 nM 25 25 0 0 0 3 6 Control 1 mM 10 M 1 nM Days Melatonin a, p<0.001 vs Control b, p<0.001 vs Melatonin 1 mM c, p<0.01 vs Melatonin 10 M Alonso-Gonz lez et al., J Pineal Res 58:189-197, 2015.
EFFECTS OF IONIZING RADIATION ON BREAST CANCER CELL PROLIFERATION (MCF-7) (% of control non radiated cells) 120 100 Cell proliferation 0 Gy 80 60 4 Gy 40 8 Gy 20 12 Gy 0 3 6 0 Days Post-Radiation Alonso-Gonz lez et al., J Pineal Res 58:189-197, 2015.
POTENTIATION OF RADIATION-INDUCED GROWTH INHIBITION BY MELATONIN 125 6 Days Post-Radiation (% of control radiated cells) 100 a Cell Proliferation a a a 75 a b c a b c 50 25 0 Before and after irradiation Before irradiation Before irradiation Before and after irradiation Before irradiation Before and after irradiation Control Melatonin 1 mM Melatonin 10 M Melatonin 1 nM a, p<0.001 vs Control b, p<0.001 vs Melatonin 1 mM c, p<0.01 vs Melatonin 10 M Alonso-Gonz lez et al., J Pineal Res 58:189-197, 2015.
CELL CYCLE DISTRIBUTION IN MCF-7 CELLS AFTER TREATMENT WITH MELATONIN (1 nM) AND IONIZING RADIATION 125 125 Melatonin pretreated cells (1 nM) Non-radiated cells Cell cycle distribution Cell cycle distribution 100 100 a 75 75 50 50 a a 25 25 0 0 G1 S G2-M G1 S G2-M 125 125 Radiated cells Melatonin Pretreated (1 nM) and Radiated cells Cell cycle distribution Cell cycle distribution 100 100 75 75 b a 50 50 a b 25 25 a b 0 0 G1 S G2-M G1 S G2-M a, p<0.001 vs Non-radiated cells b, p<0.001 vs Radiated cells Alonso-Gonz lez et al., J Pineal Res 58:189-197, 2015.
IR DNA DAMAGE DOUBLE STRAND BREAKS (DSBs) ATM MRN COMPLEX P53 CHK2 Apoptosis Senescence Cell cycle arrest DNA damage repair Genomic Integrity Restored SURVIVAL
EFFECTS OF RADIATION AND MELATONIN ON RAD51 mRNA EXPRESSION IN MCF-7 CELLS 150 125 (% of control radiated cells) 125 (% of control non-radiated cells) p<0.001 a 100 100 b c RAD51 75 b d e 75 RAD51 50 50 25 0 25 Control 1 mM 10 M 1 nM 0 Melatonin pretreatment before radiation Non-Radiated cells Radiated cells a, p<0.001 vs Control b, p<0.001 vs Melatonin 1 mM c, p<0.001 vs Melatonin 10 M RADIATION Alonso-Gonz lez et al., J Pineal Res 58:189-197, 2015.
EFFECTS OF RADIATION AND MELATONIN ON DNA-PKcs mRNA EXPRESSION IN MCF-7 CELLS 150 (% of control radiated cells) (% of control non-radiated cells) 125 125 p<0.001 100 100 DNA-PKcs a a 75 DNA-PKcs a b c 75 50 50 25 0 25 Control 1 mM 10 M 1 nM 0 Melatonin pretreatment before radiation Non-Radiated cells Radiated cells a, p<0.01 vs Control b, p<0.001 vs Control c, p<0.01 vs Melatonin 1 mM d, p<0.001 vs Melatonin 1 mM e, p<0.01 vs Melatonin 10 M RADIATION Alonso-Gonz lez et al., J Pineal Res 58:189-197, 2015.
EFFECTS OF IONIZING RADIATION AND MELATONIN ON p53 mRNA EXPRESSION IN BREAST CANCER CELLS 400 (% of control non-radiated cells) 350 a b c d 300 a b 250 a a P53 200 150 100 50 0 Control Non- Radiated cells Control radiated cells 1 mM 10 M 1 nM Melatonin pretreatment before radiation a, p<0.001 vs Control non-radiated cells b, p<0.001 vs Control radiated cells c, p<0.001 vs Melatonin 1 mM d, p<0.001 vs Melatonin 10 M RADIATION
Decreasing cell proliferation. MELATONIN PRETREATMENT SENSITIZES BREAST CANCER CELLS TO THE EFFECTS OF IONIZING RADIATION Inducing G1 cell cycle arrest. p53 Down-regulating RAD-51 and also DNA-PKcs. Two proteins involved in DSBs repair mechanisms.
RESEARCH GROUP CAROLINA ALONSO-GONZ LEZ ALICIA GONZ LEZ CABEZA CARLOS MART NEZ CAMPA JAVIER MEN NDEZ MEN NDEZ NGELA GARC A VIDAL SAMUEL COS CORRAL Technical assistance Jos Antonio de Cos Coss o Gema Viar Ru z
