This work describes different effects of K:D-Rib solution treatment: from one side the slow down of cell proliferation and the reduction of chemoinvasive potential of human breast cancer cell line (HTB-126) and from the other the maintenance of normal proliferation and normal morphology in mammary human not cancer epithelial cell line (HTB-125). K:D-Rib is a water solution of D-ribose and KHCO 3 . The role of D-ribose on the energetic metabolism and its involvement into glycogen synthesis [1, 2], as well as the importance of K + into the cell physiology, are well known [3, 4]. It has been found that K + is essential to fold and to stabilize G-quadruplex [5] with a strong relevance for telomeric structures [2, 6] and for oncogenic promoter regions. Our results showed that K:D-Rib has a cytostatic effect on canine carcinoma cell line (A72), slows the colony formation ability of the HTB-126 cell line and has an antioxidant behaviour reducing MTT salt to formazan in absence of cells [1]. These results are confirmed by our most recent work, demonstrating that 5mM K:D-Rib increase the cell cycle time of HTB-126 cell line treated with K:D-Rib at the concentration of 5mM, from 44h to 59h. Here it will be show how K:D-Rib interferes both on HTB-126 cell line proliferation and cell morphology. Results on cell morphology using Atomic Force Microscopy (AFM) are presented. K:D-Rib is tested also on human mammary epithelial cell line (HTB-125). HTB-125 cells treated with 5 mM K:D-Rib do not display toxicity or notable cell proliferation decreasing rate compared to the control one. HTB-125 cell morphology is analyzed by AFM. As mentioned before a key point of cancer cells is the capability to invade tissues nearby or far from cancer formation site. Tumour motility is an important step in the intricate process leading to the formation of metastasis. It has been shown that metastatic cells are more motile than non-metastatic tumour cells and most motile of normal cells. Metastatic cells lose growth-inhibitory responses, undergo alterations in adhesiveness and demonstrate enhanced production of enzymes that can degrade extracellular matrix components. Since the development of metastatic disease in breast cancer is one of main responsible of cancer mortality, the stopping and the understanding of the mechanisms that facilitate metastatic tumour progression is of prime importance [7]. We have investigated if K:D-Rib solution within 9 days can modify the migration and the invasion ability. The experiments show HTB-126 cells are able to migrate across the coverslip toward the FBS – agar spot and to invade it within 48, but the relative cell number inside the AGAR-FBS decrease already after five days of treatment. After nine days of treatment with K:D-Rib the relative cell number, inside the AGAR-FBS spot is reduced to 25%, demonstrating that tumorigenic potential is highly decreased with K:D-Rib treatment. These results show that 5mM K:D-Rib causes the change of some aspects like migration, invasion and proliferation of HTB-126 cell line. Despite these evidences K:D-Rib does not interfere neither with the proliferation of HTB-125 cell line nor with cell morphology. 1. Croci S, Bruni L, Bussolati S, Castaldo M, Dondi M: Potassium bicarbonate and D-ribose effects on A72 canine and HTB-126 human cancer cell line proliferation in vitro. Cancer Cell International 2011, 11. 2. Heiden MGV, Cantley LC, Thompson CB: Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation. Science 2009, 324(5930):1029-1033. 3. Dai JX CM, Yang DZ: Polymorphism of human telomeric quadruplex structures. 4. Xianfeng Zhou FS, † Yanqing Tian ,* Cody Youngbull, Roger H. Johnson, and Deirdre R. Meldrum: A New Highly Selective Fluorescent K+ Sensor. Journal of the American Chemical Society 2011(133, ):18530 – 18533. 5. Parkinson GN, Lee MPH, Neidle S: Crystal structure of parallel quadruplexes from human telomeric DNA. Nature 2002, 417(6891):876-880. 6. Lipps HJ, Rhodes D: G-quadruplex structures: in vivo evidence and function. Trends in Cell Biology 2009, 19(8):414-422. 7. Fernandis AZ, Prasad A, Band H, Klosel R, Ganju RK: Regulation of CXCR4-mediated chemotaxis and chemoinvasion of breast cancer cells. Oncogene 2004, 23(1):157-167.

K:D-Rib ON BIOLOGY OF HUMAN CANCER AND NOT CANCER CELL LINE / Bruni L. ; Croci S.. - (2013), pp. 10-11.

K:D-Rib ON BIOLOGY OF HUMAN CANCER AND NOT CANCER CELL LINE

CROCI, Simonetta
2013

Abstract

This work describes different effects of K:D-Rib solution treatment: from one side the slow down of cell proliferation and the reduction of chemoinvasive potential of human breast cancer cell line (HTB-126) and from the other the maintenance of normal proliferation and normal morphology in mammary human not cancer epithelial cell line (HTB-125). K:D-Rib is a water solution of D-ribose and KHCO 3 . The role of D-ribose on the energetic metabolism and its involvement into glycogen synthesis [1, 2], as well as the importance of K + into the cell physiology, are well known [3, 4]. It has been found that K + is essential to fold and to stabilize G-quadruplex [5] with a strong relevance for telomeric structures [2, 6] and for oncogenic promoter regions. Our results showed that K:D-Rib has a cytostatic effect on canine carcinoma cell line (A72), slows the colony formation ability of the HTB-126 cell line and has an antioxidant behaviour reducing MTT salt to formazan in absence of cells [1]. These results are confirmed by our most recent work, demonstrating that 5mM K:D-Rib increase the cell cycle time of HTB-126 cell line treated with K:D-Rib at the concentration of 5mM, from 44h to 59h. Here it will be show how K:D-Rib interferes both on HTB-126 cell line proliferation and cell morphology. Results on cell morphology using Atomic Force Microscopy (AFM) are presented. K:D-Rib is tested also on human mammary epithelial cell line (HTB-125). HTB-125 cells treated with 5 mM K:D-Rib do not display toxicity or notable cell proliferation decreasing rate compared to the control one. HTB-125 cell morphology is analyzed by AFM. As mentioned before a key point of cancer cells is the capability to invade tissues nearby or far from cancer formation site. Tumour motility is an important step in the intricate process leading to the formation of metastasis. It has been shown that metastatic cells are more motile than non-metastatic tumour cells and most motile of normal cells. Metastatic cells lose growth-inhibitory responses, undergo alterations in adhesiveness and demonstrate enhanced production of enzymes that can degrade extracellular matrix components. Since the development of metastatic disease in breast cancer is one of main responsible of cancer mortality, the stopping and the understanding of the mechanisms that facilitate metastatic tumour progression is of prime importance [7]. We have investigated if K:D-Rib solution within 9 days can modify the migration and the invasion ability. The experiments show HTB-126 cells are able to migrate across the coverslip toward the FBS – agar spot and to invade it within 48, but the relative cell number inside the AGAR-FBS decrease already after five days of treatment. After nine days of treatment with K:D-Rib the relative cell number, inside the AGAR-FBS spot is reduced to 25%, demonstrating that tumorigenic potential is highly decreased with K:D-Rib treatment. These results show that 5mM K:D-Rib causes the change of some aspects like migration, invasion and proliferation of HTB-126 cell line. Despite these evidences K:D-Rib does not interfere neither with the proliferation of HTB-125 cell line nor with cell morphology. 1. Croci S, Bruni L, Bussolati S, Castaldo M, Dondi M: Potassium bicarbonate and D-ribose effects on A72 canine and HTB-126 human cancer cell line proliferation in vitro. Cancer Cell International 2011, 11. 2. Heiden MGV, Cantley LC, Thompson CB: Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation. Science 2009, 324(5930):1029-1033. 3. Dai JX CM, Yang DZ: Polymorphism of human telomeric quadruplex structures. 4. Xianfeng Zhou FS, † Yanqing Tian ,* Cody Youngbull, Roger H. Johnson, and Deirdre R. Meldrum: A New Highly Selective Fluorescent K+ Sensor. Journal of the American Chemical Society 2011(133, ):18530 – 18533. 5. Parkinson GN, Lee MPH, Neidle S: Crystal structure of parallel quadruplexes from human telomeric DNA. Nature 2002, 417(6891):876-880. 6. Lipps HJ, Rhodes D: G-quadruplex structures: in vivo evidence and function. Trends in Cell Biology 2009, 19(8):414-422. 7. Fernandis AZ, Prasad A, Band H, Klosel R, Ganju RK: Regulation of CXCR4-mediated chemotaxis and chemoinvasion of breast cancer cells. Oncogene 2004, 23(1):157-167.
K:D-Rib ON BIOLOGY OF HUMAN CANCER AND NOT CANCER CELL LINE / Bruni L. ; Croci S.. - (2013), pp. 10-11.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2729714
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