Role of Autophagy in the Response of Hs578t Breast Tumor Cells to Radiation - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Role of Autophagy in the Response of Hs578t Breast Tumor Cells to Radiation write by Shweta Moreshwar Chakradeo. This book was released on 2012. Role of Autophagy in the Response of Hs578t Breast Tumor Cells to Radiation available in PDF, EPUB and Kindle. Breast cancer is the most commonly observed cancer type in women and is the second leading cause of cancer death in women. Radiation can be used to debulk tumors prior to surgery as well as to treat patients after surgery and/or chemotherapy. Previous studies from our laboratory have shown that the anti -- malarial drug chloroquine sensitizes breast cancer cell lines to radiation by suppression of autophagy which is a conservative catabolic process that can be cytoprotective. The scientific literature has demonstrated that many tumor cell systems undergo cytoprotective autophagy and that pharmacological or genetic inhibition of autophagy leads to other modes of cell death such as apoptosis. Acridine orange staining was used for determination of acidic vacuole formation, an indication of autophagy and DAPI/TUNEL staining was used to identify apoptotic cells. Our studies in Hs578t breast tumor cells show the lack of sensitization by chloroquine upon autophagy inhibition with minimal apoptosis when cells are treated with 5 × 2Gy radiation. The extent of apoptosis was not increased upon autophagy inhibition by Chloroquine as determined by DAPI/TUNEL assays and quantified by Flow Cytometry using AnnexinV/PI. The potential role of senescence in the effects of radiation in the Hs578t cells was determined with the use of [beta]-Galactosidase dye staining for senescence. It appears from these studies that autophagy need not to be cytoprotective in all breast cancer cell lines. Additional studies are in progress to effort to identify the factors that might distinguish between cytoprotective and non-cytoprotective autophagy.
Irradiation of Hs578t Breast Tumor Cells Induces Non-cytoprotective Autophagy
Irradiation of Hs578t Breast Tumor Cells Induces Non-cytoprotective Autophagy - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Irradiation of Hs578t Breast Tumor Cells Induces Non-cytoprotective Autophagy write by Aisha Alhaddad. This book was released on 2014. Irradiation of Hs578t Breast Tumor Cells Induces Non-cytoprotective Autophagy available in PDF, EPUB and Kindle. Cancer is the second most common cause of death in the US. The most frequently observed cancer type in women is breast cancer. A special type of breast cancer is triple negative (TNBC) cancer that is characterized by lacking three receptors: estrogen, progesterone and human epithelial growth factor (HER 2). The HS578t breast cell line is a model of TNBC that also has a mutation of the p53 protein. Ionizing radiation is used widely in the clinic to debulk tumors before surgery as well as post-surgery to eliminate residual tumor cells outside the surgical field. Previous studies from our laboratory showed that inhibition of autophagy does sensitize p53 wild type MCF-7 and ZR-75 breast tumor cells to radiation. However, this is not necessarily the response in all breast cell lines. The Hs578t cells did not appear to be sensitized to radiation after inhibition of autophagy using chloroquine as a pharmacological inhibitor. The present study was designed to build upon these previous findings and further confirm that the Hs578t breast cell line could not be sensitized to radiation through autophagy inhibition. Time course studies showed a reduction of viable cell number upon irradiation of Hs578t breast tumor cells and that both autophagy and senescence were induced. Acridine orange staining was used to examine the acidic vacuole formation while [beta]-galactosidase staining indicated the promotion of senescence. Flow cytometry was used to quantify both autophagy and senescence. Inhibition of autophagy using pharmacological inhibitors such as ammonium chloride, or genetic silencing of autophagy by beclin1, which is a protein initiator of autophagy, did not sensitize Hs578t breast tumor cells to irradiation. It shows from these studies that autophagy is not necessarily cytoprotective in all breast cancer cell lines, which should be considered in current clinical trials designed to sensitize tumor cells to chemotherapy and radiation through inhibition of autophagy.
Role of Autophagy in Radiosensitization of Breast Tumor Cells
Role of Autophagy in Radiosensitization of Breast Tumor Cells - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Role of Autophagy in Radiosensitization of Breast Tumor Cells write by Molly L. Bristol. This book was released on 2011. Role of Autophagy in Radiosensitization of Breast Tumor Cells available in PDF, EPUB and Kindle. In MCF-7 breast tumor cells, ionizing radiation promoted autophagy that was cytoprotective; pharmacological or genetic interference with autophagy induced by radiation resulted in growth suppression and/or cell killing (primarily by apoptosis). The hormonally active form of vitamin D, 1,25D3, also promoted autophagy in irradiated MCF-7 cells, sensitized the cells to radiation and suppressed the proliferative recovery that occurs after radiation alone. 1,25D3 also enhanced radiosensitivity and promoted autophagy in MCF7 cells that overexpress Her-2/neu as well as in p53 mutant Hs578t breast tumor cells. In contrast, 1,25D3 failed to alter radiosensitivity or promote autophagy in the BT474 breast tumor cell line with low-level expression of the vitamin D receptor. Enhancement of MCF-7 cell sensitivity to radiation by 1,25D3 was not attenuated by either a pharmacological or genetic block to autophagy; this was due largely to the promotion of apoptosis via the suppression of protective autophagy that occurs in response to radiation alone. Moreover, pharmacological blockade of autophagy did not sensitize noncancerous MCF10a cells to radiation; conversely, 4T1 mouse mammary tumors were highly sensitive to pharmacological inhibition of autophagy, suggesting selective radiosensitization against cancer cell lines. The current studies are consistent with the premise that while autophagy mediates a cytoprotective function in irradiated breast tumor cells, promotion of autophagy can also confer radiosensitivity by vitamin D (1,25D3). In addition, this work highlights the technical challenge of establishing the potential cytotoxic function of autophagy in an experimental system where the cytoprotective function may be concurrently expressed.
The Role of Cytoprotective and Non-protective Autophagy in Radiation Sensitivity in Breast Tumor Cells
The Role of Cytoprotective and Non-protective Autophagy in Radiation Sensitivity in Breast Tumor Cells - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook The Role of Cytoprotective and Non-protective Autophagy in Radiation Sensitivity in Breast Tumor Cells write by Jade Ngoc Le. This book was released on 2014. The Role of Cytoprotective and Non-protective Autophagy in Radiation Sensitivity in Breast Tumor Cells available in PDF, EPUB and Kindle. In general, ionizing radiation promotes cytoprotective autophagy in a majority of breast tumor cells. Previous studies from our laboratory indicated that radiation (5x2 Gy) induces cytoprotective autophagy in MCF-7 cells. In the current work, inhibition of autophagy by silencing of Beclin-1 in MCF-7 cells resulted in an increase in sensitivity to radiation based both on cell number and clonogenic survival; however, there was no increase in apoptosis and the basis for this sensitization is currently under investigation. Unexpectedly, enhancement of autophagy by silencing of Bcl-2 also led to an increase in sensitivity to radiation, possibly through the conversion of cytoprotective to cytostatic autophagy. In contrast to the MCF-7 cells, radiation (5x2 Gy) induces non-protective autophagy in Hs578t cells. Interference with autophagy through silencing of Beclin-1 or induction of Bcl-2 did not alter radiation sensitivity in the Hs578t cells. Since the induction of cytoprotective autophagy can represent an impediment to radiation therapy, it is important to understand the types of autophagy that occur in response to radiation in specific cellular settings and whether interference with autophagy can increase sensitivity to different forms of cancer treatment.
Autophagy
Autophagy - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Autophagy write by David A. Gewirtz. This book was released on 2013-07-29. Autophagy available in PDF, EPUB and Kindle. There is currently a great deal of interest in autophagy, a process whereby a cell digests its constituents to generate energy and metabolic precursors under conditions of stress such as nutrient deprivation. Autophagy may serve as a mechanism for protection of the tumor cell from the effects of radiation and chemotherapy, but may also mediate tumor cell death in response to these challenges. Accumulating evidence indicates that autophagy is also a fundamental characteristic of stem cells, including tumor stem cells. As tumor stem cells are likely to play a central role in tumor dormancy, it appears that autophagy could contribute to the capacity of tumor stem cells to survive for extended periods of time in a dormant state and eventually give rise to recurrent tumors that are primary determinants of morbidity and mortality in cancer patients.
