Inhibition of autophagy sensitizes cancer cells to Photofrin-based photodynamic therapy

BMC Cancer
Antoni DomagalaMalgorzata Firczuk

Abstract

Accumulating evidence suggest that autophagy plays a pivotal role in various anticancer therapies, including photodynamic therapy (PDT), acting as a pro-death or pro-survival mechanism in a context-dependent manner. Therefore, we aimed to determine the role of autophagy in Photofrin-based PDT. In vitro cytotoxic/cytostatic effects of PDT were evaluated with crystal violet cell viability assay. Autophagy induction was analyzed by immunoblotting and immunofluorescence using anti-LC3 antibody. Autophagy was inhibited by shRNA-mediated ATG5 knockdown or CRISPR/Cas9-mediated ATG5 knockout. Apoptosis was assessed by flow cytometry analysis of propidium iodide and anexin V-positive cells as well as by detection of cleaved PARP and caspase 3 proteins using immunoblotting. Protein carbonylation was evaluated by the 2,4-dinitrophenylhydrazine (DNPH) method. Photofrin-PDT leads to robust autophagy induction in two cancer cell lines, Hela and MCF-7. shRNA-mediated knockdown of ATG5 only partially blocks autophagic response and only marginally affects the sensitivity of Hela and MCF-7 cells to PDT. ATG5 knockout in HeLa cell line utilizing CRISPR/Cas9 genome editing results in increased PDT-mediated cytotoxicity, which is accompanied by an ...Continue Reading

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Citations

Oct 26, 2018·Cancer Chemotherapy and Pharmacology·Chao-Yue SunBing Feng
Oct 6, 2018·Apoptosis : an International Journal on Programmed Cell Death·Xian DuanJun He
Aug 4, 2018·International Journal of Molecular Sciences·Antoni DomagalaMalgorzata Firczuk
Nov 19, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Eric Chekwube AniogoHeidi Abrahamse
Feb 9, 2021·Frontiers in Oncology·Waleska K MartinsTayana M Tsubone
Nov 8, 2020·Archives of Biochemistry and Biophysics·Tayana Mazin TsuboneMauricio S Baptista
Jul 6, 2021·Chemical Society Reviews·Jianlei XieJong Seung Kim
Jul 14, 2021·Annual Review of Biomedical Engineering·Deanna BroadwaterSophia Y Lunt
Aug 17, 2021·Journal of Photochemistry and Photobiology. B, Biology·Sara R D GamelasMaria A F Faustino
Apr 4, 2020·Anti-cancer Agents in Medicinal Chemistry·Ahmed El-HusseinPatience Mthunzi-Kufa

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Methods Mentioned

BETA
Protein
electrophoresis
PCR
flow cytometry

Software Mentioned

Zen
GraphPad Prism

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