ESR study of plasmatic membrane of the transplantable melanoma cells in relation to their biological properties

Kozłowska, K; Nowak, Jerzy Z.; Kwiatkowski, Bartłomiej; Cichorek, M

doi:10.1016/s0940-2993(99)80074-8

Cited by 34 publications

(18 citation statements)

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“…In accordance with studies on other CAPs, the specificity of LTX-315 for tumor cells is probably due to differences in cell membrane composition between cancer cells and non-malignant cells. Cancer cells have been shown to have a larger quantity of anionic molecules on their membrane [13, 14, 16], in addition to an increased membrane fluidity [17, 18] and membrane cell surface due to more microvilli [19, 20]. The cytotoxicity of LTX-315 was somewhat similar toward human melanoma cells (A375) and normal human primary melanocytes (PCS-200-013).…”

Section: Discussionmentioning

confidence: 99%

“…Additional factors that may contribute to the selective killing of cancer cells by ACPs include membrane fluidity and cell surface area. Compared to non-malignant cells, cancer cells often have a greater membrane fluidity [17, 18] and cell surface area (additional microvilli) [19, 20], hence leading to an improved anticancer activity of ACPs due to an increased membrane destabilization and the ability to bind more ACP molecules. Moreover, ACPs kill both drug-sensitive and drug-resistant cancer cells due to their membranolytic mode of action, independently of proliferative status and resistance phenotype [21, 22].…”

Section: Introductionmentioning

confidence: 99%

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Complete regression and systemic protective immune responses obtained in B16 melanomas after treatment with LTX-315

Camilio

Berge

Ravuri

et al. 2014

Cancer Immunol Immunother

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Malignant melanoma is the most aggressive and deadliest form of skin cancer due to its highly metastatic potential, which calls for new and improved therapies. Cationic antimicrobial peptides (CAPs) are naturally occurring molecules found in most species, in which they play a significant role in the first line of defense against pathogens, and several CAPs have shown promising potential as novel anticancer agents. Structure–activity relationship studies on the CAP bovine lactoferricin allowed us to de novo design short chemically modified lytic anticancer peptides. In the present study, we investigated the in vivo antitumor effects of LTX-315 against intradermally established B16 melanomas in syngeneic mice. Intratumoral administration of LTX-315 resulted in tumor necrosis and the infiltration of immune cells into the tumor parenchyma followed by complete regression of the tumor in the majority of the animals. LTX-315 induced the release of danger-associated molecular pattern molecules such as the high mobility group box-1 protein in vitro and the subsequent upregulation of proinflammatory cytokines such as interleukin (IL) 1β, IL6 and IL18 in vivo. Animals cured by LTX-315 treatment were protected against a re-challenge with live B16 tumor cells both intradermally and intravenously. Together, our data indicate that intratumoral treatment with LTX-315 can provide local tumor control followed by protective immune responses and has potential as a new immunotherapeutic agent.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-014-1540-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Complete regression and systemic protective immune responses obtained in B16 melanomas after treatment with LTX-315

Camilio

Berge

Ravuri

et al. 2014

Cancer Immunol Immunother

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“…Histological structure and ultrastructure [19] Membrane fluidity and molecular mobility in the plasmatic membrane [24] Lowering of the degree of order in the phospholipid bilayer; increase in membrane fluidity and reduction in molecular mobility dynamics within it…”

Section: /Zarzeczna/cichorekmentioning

confidence: 99%

Sensitivity of Transplantable Melanoma Cells to Cytokines with Regard to Their Spontaneous Apoptosis

2001

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Objectives: Changes in the sensitivity of two lines of transplantable melanoma cells to the antiproliferative activity of interleukin 6 (IL-6), oncostatin M (OSM), tumor necrosis factor-α (TNF-α) during melanoma progression were the subject of this study. We were looking for a correlation between these changes and the ability of melanoma cells to undergo spontaneous apoptosis. Methods: The influence of exogenous cytokines on the proliferation of melanoma cells was measured by colorimetric methods with MTT and apoptosis of these cells was estimated by staining with annexin V/propidium iodide, measurement of DNA degradation and cell cycle analysis. Results: It was observed that during melanoma progression the sensitivity of those two melanoma line cells to the antiproliferative effect of IL-6 and OSM did not change, while a spontaneous alteration of the melanotic line into an amelanotic one seemed to be accompanied by resistance of the amelanotic melanoma cells to the antiproliferative activity of TNF-α. Simultaneously, we observed a decreased ability of amelanotic melanoma cells (in comparison with the native line) to undergo spontaneous apoptosis. Conclusions: The observed resistance to the TNF-α antiproliferative effect which appears during melanoma progression seems to be correlated with a lower ability of the amelanotic melanoma cells to undergo spontaneous apoptosis.

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“…Upon binding to cell membranes, hydrophobicity of molecules becomes very crucial to determine how well it permeates such membrane. [139][140][141] In addition, membrane fluidity is typically increased in cancer cells relative to their healthy counterparts, 142,143 which may facilitate cancer cell membrane destabilization by membrane-bound CADs.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and antitumor properties of glycosylated antitumor ether lipid (GAEL)- chlorambucil-hybrids

Idowu

Samadder

Arthur

et al. 2016

Chemistry and Physics of Lipids

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The development of resistance to apoptotic pathways by cancer cells is one of the great impediments to the successful use of chemotherapeutic agents. The development of resistance may be attributed to the role of cancer stem cells in the progression of this disease. One approach to combat drug resistance involves the use of drug combinations that impact multiple targets simultaneously. Although this is believed to be better at controlling complex disease systems, it has often proven to be of limited benefits in terms of overall therapeutic outcomes in cancer treatment. Glycosylated antitumor ether lipids (GAELs) are an emerging class of novel anticancer molecules that is being investigated as potential anticancer drugs. Interest in this class of drug is based on their ability to kill cancer stem cells as well as their non-apoptotic mechanism of action. This provides new opportunities to manipulate cell death in a therapeutic context, especially the renewed ability to kill apoptosis-resistant cancer cells. We therefore hypothesized that hybrid molecules that combine apoptosis-dependent and apoptosis-independent mode of actions in a single molecule may lead to better therapeutic outcomes. We also posited that the amphiphilic nature of GAELs could be modulated and fine-tuned to give a more potent analog.This dissertation describes the antitumor activities of different analogs of GAELchlorambucil hybrids and different triamino analogs. In all, eleven GAEL analogs were synthesized. Their activities, as well as that of reference compounds, were assessed against breast (JIMT1, MDA-MB-231, BT474), pancreas (MiaPaCa2) and prostate (DU145, PC3) cancer cell lines using the MTS assay. Our results reveal that the hybrid concept is a potential viable avenue to pursue as a therapeutic option especially when the other domain is carefully selected (Chapter 3). Moreover, the evidently more potent triamino analog not only corroborate the plausibility of a hybrid drug, it also revealed an important detail about the amphiphilic-cytotoxic relationships of GAELs (Chapter 4). iv ACKNOWLEDGEMENTSMy heartfelt appreciation goes to my indefatigable supervisor, Dr. Frank Schweizer, for his unquantifiable support and understanding, and also for guiding my feet through the 'wilderness' of organic synthesis. His astuteness, inquisitiveness, resourcefulness and right amount of scientific skepticism have rightly shaped me in the pursuit of excellence. He is ever ready and willing to help whenever I run into troubled waters.Also to my co-supervisor, my committee member and our long-standing collaborator, Dr.Gilbert Arthur: his calmness, dexterity, and keen attention to details are unparalleled and 'contagious'. The invaluable contributions of Dr. Pranati Samadder to the success of this work are also deeply appreciated.Many thanks to members of my examining committee: Drs. Jorg Stetefeld, Rebecca Davis and Gilbert Arthur, for your patience, constructive feedbacks and quick response whenever I beckon on you. It was a delight having you all ...

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ESR study of plasmatic membrane of the transplantable melanoma cells in relation to their biological properties

Cited by 34 publications

References 11 publications

Complete regression and systemic protective immune responses obtained in B16 melanomas after treatment with LTX-315

Complete regression and systemic protective immune responses obtained in B16 melanomas after treatment with LTX-315

Sensitivity of Transplantable Melanoma Cells to Cytokines with Regard to Their Spontaneous Apoptosis

Design, synthesis and antitumor properties of glycosylated antitumor ether lipid (GAEL)- chlorambucil-hybrids

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