Coherence-controlled holographic microscopy enabled recognition of necrosis as the mechanism of cancer cells death after exposure to cytopathic turbid emulsion

Abstract. Coherence-controlled holographic microscopy (CCHM) in low-coherence mode possesses a pronounced coherence gate effect. This offers an option to investigate the details of cellular events leading to cell death caused by cytopathic turbid emulsions. CCHM capacity was first assessed in model situations that showed clear images obtained with low coherence of illumination but not with high coherence of illumination. Then, the form of death of human cancer cells induced by treatment with biologically active phospholipids (BAPs) preparation was investigated. The observed overall retraction of cell colony was apparently caused by the release of cell-to-substratum contacts. This was followed by the accumulation of granules decorating the nuclear membrane. Then, the occurrence of nuclear membrane indentations signaled the start of damage to the integrity of the cell nucleus. In the final stage, cells shrunk and disintegrated. This indicated that BAPs cause cell death by necrosis and not apoptosis. An intriguing option of checking the fate of cancer cells caused by the anticipated cooperative effect after adding another tested substance sodium dichloroacetate to turbid emulsion is discussed on grounds of pilot experiments. Such observations should reveal the impact and mechanism of action of the interacting drugs on cell behavior and fate that would otherwise remain hidden in turbid milieu.

[1]  E. Wolf,et al.  Principles of Optics (7th Ed) , 1999 .

[2]  Vittorio Bianco,et al.  Clear coherent imaging in turbid microfluidics by multiple holographic acquisitions. , 2012, Optics letters.

[3]  Thomas Kreis,et al.  Digital holographic interference-phase measurement using the Fourier-transform method , 1986 .

[4]  G Indebetouw,et al.  Imaging through scattering media with depth resolution by use of low-coherence gating in spatiotemporal digital holography. , 2000, Optics letters.

[5]  P. Hogg,et al.  Dual-targeting of aberrant glucose metabolism in glioblastoma , 2015, Journal of Experimental & Clinical Cancer Research.

[6]  Guido Kroemer,et al.  Cell death by necrosis: towards a molecular definition. , 2007, Trends in biochemical sciences.

[7]  J. Čolláková,et al.  The Role of Coherence in Image Formation in Holographic Microscopy , 2014 .

[8]  E. Leith,et al.  Optical sectioning by holographic coherence imaging: a generalized analysis. , 2003, Journal of the Optical Society of America. A, Optics, image science, and vision.

[9]  Radim Chmelik,et al.  Proving tumour cells by acute nutritional/energy deprivation as a survival threat: a task for microscopy. , 2009, Anticancer research.

[10]  Michael R. Melloch,et al.  Photorefractive holography for imaging through turbid media using low coherence light , 2000 .

[11]  P. Ferraro,et al.  Microscopy imaging and quantitative phase contrast mapping in turbid microfluidic channels by digital holography. , 2012, Lab on a chip.

[12]  B. Coomber,et al.  Sodium dichloroacetate (DCA) reduces apoptosis in colorectal tumor hypoxia. , 2010, Cancer letters.

[13]  R. Chmelík,et al.  Coherence-controlled holographic microscopy in diffuse media. , 2014, Optics express.

[14]  Etienne Cuche,et al.  Time-domain optical coherence tomography with digital holographic microscopy. , 2005, Applied optics.

[15]  T Zikmund,et al.  Sequential processing of quantitative phase images for the study of cell behaviour in real‐time digital holographic microscopy , 2014, Journal of microscopy.

[16]  U. Massing,et al.  Health effects of dietary phospholipids , 2012, Lipids in Health and Disease.

[17]  J. Mackey,et al.  Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer , 2008, British Journal of Cancer.

[18]  R Birngruber,et al.  Contrast limits of coherence-gated imaging in scattering media. , 1997, Applied optics.

[19]  Jingang Zhong,et al.  Dynamic imaging through turbid media based on digital holography. , 2014, Journal of the Optical Society of America. A, Optics, image science, and vision.

[20]  Barry R. Masters,et al.  Quantitative Phase Imaging of Cells and Tissues , 2012 .

[21]  H. G. Davies,et al.  The Use of the Interference Microscope to Determine Dry Mass in Living Cells and as a Quantitative Cytochemical Method , 1954 .

[22]  J. Mackey,et al.  A phase I open-labeled, single-arm, dose-escalation, study of dichloroacetate (DCA) in patients with advanced solid tumors , 2015, Investigational New Drugs.

[23]  Dennis C. Ghiglia,et al.  Two-Dimensional Phase Unwrapping: Theory, Algorithms, and Software , 1998 .

[24]  D. Jayne,et al.  Dichloroacetate induces apoptosis and cell-cycle arrest in colorectal cancer cells , 2010, British Journal of Cancer.

[25]  M. Rubenstein,et al.  In vitro effects of dichloroacetate and CO2 on hypoxic HeLa cells. , 2009, Anticancer research.

[26]  G. Dunn,et al.  Microinterferometry of the movement of dry matter in fibroblasts. , 1989, Journal of cell science.

[27]  Christian Depeursinge,et al.  Noninvasive characterization of the fission yeast cell cycle by monitoring dry mass with digital holographic microscopy. , 2009, Journal of biomedical optics.

[28]  R. Chmelík,et al.  Off-axis setup taking full advantage of incoherent illumination in coherence-controlled holographic microscope. , 2013, Optics express.

[29]  Radim Chmelík,et al.  Coherence-controlled holographic microscope , 2010, Polish-Slovak-Czech Optical Conference on Wave and Quantum Aspects of Contemporary Optics.

[30]  Radim Chmelík,et al.  Coherence-controlled holographic microscope. , 2010, Optics express.

[31]  P. Veselý,et al.  Egg yolk phospholipids enriched with 1-O-octadecyl-2-oleoyl-sn-glycero-3-phospho-(N-palmitoyl) ethanolamine inhibit development of experimentally induced tumours. , 2014, Folia biologica.

[32]  Emmett N. Leith,et al.  Imaging through scattering media with holography , 1992 .