Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/119838
Title: STUDY THE INVOLVEMENT OF LYSOSOMAL CALCIUM SIGNALING IN THE ANTI-CANCER ACTIVITY OF THE LANTHANIDE PR-MPO
Authors: LIU DAN
Keywords: cancer, cell death, lysosome, calcium, lanthanide, autophagy
Issue Date: 14-Jan-2015
Citation: LIU DAN (2015-01-14). STUDY THE INVOLVEMENT OF LYSOSOMAL CALCIUM SIGNALING IN THE ANTI-CANCER ACTIVITY OF THE LANTHANIDE PR-MPO. ScholarBank@NUS Repository.
Abstract: WE SYNTHESIZED A CONJUGATE OF THE LANTHANIDE, PRASEODYMIUM (141PR), AND OBSERVED REMARKABLE ANTI-TUMOR ACTIVITY IN 2 MURINE XENOGRAFT MODELS (COLORECTAL AND PROSTATE CANCER), WITH MINIMAL OFF TARGET EFFECTS. IMPORTANTLY, PR-MERCAPTOPYRIDINE OXIDE (PR-MPO) ELICITED STRONG ANTI-CANCER ACTIVITY (IC50~2.5UM) AGAINST A HOST OF HUMAN CANCER CELL LINES INCLUDING CISPLATIN RESISTANT, P53-/- AND/OR BAX-/- VARIANTS. INTERESTINGLY, PR-MPO INDUCED A SIGNIFICANT INCREASE IN INTRACELLULAR CALCIUM FLUORESCENCE, MEASURED BY TIME RESOLVED LIVE IMAGING, HOWEVER, UNLIKE THAPSIGARGIN, THE INCREASE IN CALCIUM WAS NOT MEDIATED BY ER CALCIUM STORES. INSTEAD, A SIGNIFICANT INCREASE IN CALCIUM FLUORESCENCE (PUNCTA) WAS OBSERVED WITHIN MINUTES, A PATTERN DISTINCTLY DIFFERENT FROM THE DIFFUSE CYTOSOLIC INCREASE UPON DEPLETING ER CALCIUM. NOTABLY, CHELATION OF EXTRACELLULAR CALCIUM ABROGATED THE INCREASE IN INTRACELLULAR CALCIUM AS WELL AS RESCUED CELLS FROM PR-MPO-INDUCED CELL DEATH, THUS SUGGESTING THE INVOLVEM
URI: http://scholarbank.nus.edu.sg/handle/10635/119838
Appears in Collections:Ph.D Theses (Open)

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