Cancer and cancer stem cell targeting agents: A focus on salinomycin and apoptin Jangamreddy,
نویسندگان
چکیده
......................................................................................................................................5 Abbreviations ...........................................................................................................................6 Manuscripts...............................................................................................................................8 Introduction ........................................................................................................................... 11 Hijacking the cancer signatures: Therapeutics.................................................................... 12 Cancer stem cells and cancer recurrence: ............................................................................. 14 Targeting cancer stem cells ........................................................................................................ 18 Salinomycin:..................................................................................................................................... 19 Salinomycin as anti-‐cancer stem cell therapeutic drug:..............................................................20 Apoptin: ............................................................................................................................................. 21 Thesis objectives: ................................................................................................................. 24 Aims of the manuscripts: ................................................................................................... 24 Methods ................................................................................................................................... 25 Cells and cell culture: .................................................................................................................... 25 Human CML patient and normal primary samples: ........................................................... 25 Estimation of autophagic flux by flow cytometry:............................................................... 25 Live Cell Imaging: ........................................................................................................................... 29 Results and Discussion ....................................................................................................... 30 Manuscript 1: Salinomycin induces activation of autophagy, mitophagy and affects mitochondrial polarity: Differences between primary and cancer cells .................... 30 Manuscript 2: Monitoring of autophagy is complicated: Salinomycin as an example. .............................................................................................................................................................. 32 Manuscript 3: Glucose starvation-mediated inhibition of autophagy promotes cancer cell-specific multiplicity of cell death after salinomycin treatment. .............. 33 Manuscript 4: Identification of the apoptin minimal region and its requirement for interaction with BCR-ABL1 to inhibit downstream signaling......................................... 34 General Discussion............................................................................................................... 35 Salinomycin: Autophagy, mitochondrial polarity, and differential stress responses. .............................................................................................................................................................. 35 Apoptin derived peptides: Anti-cancer stem cell agent: ................................................... 38 Conclusions............................................................................................................................. 40 References .............................................................................................................................. 43
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