Inhibition of hypoxia-inducible factor 1 with acriflavine sensitizes hypoxic tumor cells to photodynamic therapy with zinc phthalocyanine-encapsulating cationic liposomes

Broekgaarden, Mans; Weijer, Ruud; Krekorian, Massis; IJssel, Bas van den; Kos, Milan; Alles, Lindy K.; Wijk, Albert C. van; Bikádi, Zsolt; Hazai, Eszter; Gulik, Thomas M. van; Heger, Michal

doi:10.1007/s12274-016-1059-0

Cited by 89 publications

(76 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Photodynamic therapy (PDT) uses light exposure to activate a tumor-localized photosensitizer causing production of reactive oxygen species that damage tumor vasculature and promotes tumor cell death; however it is accompanied by HIF-1 stabilization which promotes tumor cell survival. In A431 tumor cells, inhibition of HIF-1 with acriflavine increased PDT-induced tumor cell death [46]. Thus acriflavine may be useful for treatment of some tumors.…”

Section: Discussionmentioning

confidence: 99%

The HIF-1 antagonist acriflavine: visualization in retina and suppression of ocular neovascularization

et al. 2016

View full text Add to dashboard Cite

Acriflavine, a fluorescent drug previously used for bacterial and trypanosomal infections, reduces hypoxia-inducible factor-1 (HIF-1) and HIF-2 transcriptional activity. In mice with oxygen-induced ischemic retinopathy, intraocular or intraperitoneal injections of acriflavine caused dose-dependent suppression of retinal neovascularization (NV) and significantly reduced expression of HIF-1-responsive genes. Intraocular injection of 100 ng caused inner retina fluorescence within 1 hour that was seen throughout the entire retina between 1 and 5 days, and at 7 days after injection, strongly suppressed choroidal NV at Bruch’s membrane rupture sites. After suprachoroidal injection of 300 ng in rats, there was retinal fluorescence in the quadrant of the injection at 1 hour that spread throughout the entire retina and choroid by 1 day, was detectable for 5 days, and dramatically reduced choroidal NV 14 days after rupture of Bruch’s membrane. After topical administration of acriflavine in mice, fluorescence was seen in the retina and retinal pigmented epithelium within 5 minutes and was detectable for 6–12 hours. Administration of 0.5% drops to the cornea twice a day, significantly reduced choroidal NV in mice. Electroretinographic b-wave amplitudes were normal 7 days after intravitreous injection of 100 ng of acriflavine in mice, showed mild threshold reductions at highest stimulus intensities after injection of 250 ng, and more extensive changes after injection of 500 ng. These data provide additional evidence for an important role for HIF-1 in retinal and choroidal NV and suggest that acriflavine can target HIF-1 through a variety of modes of administration and has good potential to provide a novel therapy for retinal and choroidal vascular diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

The HIF-1 antagonist acriflavine: visualization in retina and suppression of ocular neovascularization

et al. 2016

View full text Add to dashboard Cite

show abstract

“…One potential strategy to optimize PDT is using pharmacological adjuvants that inhibit post-PDT survival signaling, which may be co-administered with the photosensitizer [11–13]. This study was conducted to determine which pathways are activated and hence eligible for pharmacological targeting.…”

Section: Discussionmentioning

confidence: 99%

“…Whereas overexpression of HIF-1 was associated with therapeutic resistance in 5-aminolevulinic acid (5-ALA)-PDT-treated human esophageal carcinoma cells [56], combination therapy of siRNA-mediated knockdown of HIF-1 with Photosan-PDT significantly improved therapeutic efficacy in human head-and-neck cancer (SCC4, SAS) tumor-bearing mice [57]. Corroboratively, treatment of A431 and SK-ChA-1 cells with the HIF-1 inhibitor acriflavine significantly improved PDT efficacy [11, 13]. Similarly, it was shown in various studies that combined treatment comprising NF-кB inhibitors and PDT augmented therapeutic efficacy [35, 58, 59].…”

Section: Discussionmentioning

confidence: 99%

“…ZPCLs were composed of DPPC, DC-cholesterol, cholesterol, and DSPE-PEG (66:25:5:4, molar ratio) and prepared by the lipid film hydration technique as described previously [13, 16]. Physiological buffer composed of 10 mM HEPES, 0.88% (w/v) NaCl, pH = 7.4, 0.293 osmol/kg [14] was used as hydration solution.…”

Section: Methodsmentioning

confidence: 99%

“…Liposomal formulations were purged with nitrogen gas and stored at 4 °C in the dark. Under these conditions the liposomal ZnPC remains stable for at least 56 days [13]. …”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Multi-OMIC profiling of survival and metabolic signaling networks in cells subjected to photodynamic therapy

Weijer

Clavier

Zaal

et al. 2016

Cell. Mol. Life Sci.

Self Cite

View full text Add to dashboard Cite

Photodynamic therapy (PDT) is an established palliative treatment for perihilar cholangiocarcinoma that is clinically promising. However, tumors tend to regrow after PDT, which may result from the PDT-induced activation of survival pathways in sublethally afflicted tumor cells. In this study, tumor-comprising cells (i.e., vascular endothelial cells, macrophages, perihilar cholangiocarcinoma cells, and EGFR-overexpressing epidermoid cancer cells) were treated with the photosensitizer zinc phthalocyanine that was encapsulated in cationic liposomes (ZPCLs). The post-PDT survival pathways and metabolism were studied following sublethal (LC50) and supralethal (LC90) PDT. Sublethal PDT induced survival signaling in perihilar cholangiocarcinoma (SK-ChA-1) cells via mainly HIF-1-, NF-кB-, AP-1-, and heat shock factor (HSF)-mediated pathways. In contrast, supralethal PDT damage was associated with a dampened survival response. PDT-subjected SK-ChA-1 cells downregulated proteins associated with EGFR signaling, particularly at LC90. PDT also affected various components of glycolysis and the tricarboxylic acid cycle as well as metabolites involved in redox signaling. In conclusion, sublethal PDT activates multiple pathways in tumor-associated cell types that transcriptionally regulate cell survival, proliferation, energy metabolism, detoxification, inflammation/angiogenesis, and metastasis. Accordingly, tumor cells sublethally afflicted by PDT are a major therapeutic culprit. Our multi-omic analysis further unveiled multiple druggable targets for pharmacological co-intervention.Electronic supplementary materialThe online version of this article (doi:10.1007/s00018-016-2401-0) contains supplementary material, which is available to authorized users.

show abstract

An Alternating Irradiation Strategy‐Driven Combination Therapy of PDT and RNAi for Highly Efficient Inhibition of Tumor Growth and Metastasis

Dong

Cai

Fan

et al. 2020

Adv Healthcare Materials

View full text Add to dashboard Cite

Hypoxia and hypoxia induced overexpression of vascular endothelial growth factor (VEGF) not only seriously affects the treatment effects of photodynamic therapy (PDT) but also promotes tumor metastasis. Herein, an alternating irradiation strategy (referred to as alternate use of low/high dose of light [ALHDL] irradiation)-driven combination therapy of PDT and RNA interference (RNAi) is developed to synergistically inhibit tumor growth and metastasis. A cationic amphipathic peptide (ALS) served as a carrier in the co-delivery system of photochlor (HPPH) and siVEGF (ALSH/siVEGF). At the beginning of ALHDL-driven ALSH/siVEGF treatment, short-term LDL irradiation can facilitate the tumor penetration, cellular uptake, and endosome escape of ALSH/siVEGF. Moreover, accompanied by HDL-mediated rapid cell apoptosis and LDL-mediated efficient VEGF silencing, the joint use of PDT and RNAi achieved remarkable antitumor effects both in vitro and in vivo. Importantly, benefited from the excellent performance of ALHDL in slowing the rapid deterioration of the anoxic environment of tumors, and ALSH/siVEGF treatment-mediated highly improved VEGF silencing efficacy and inhibitory effect on angiogenesis, the liver and lung metastases of HeLa cells have been successfully suppressed. Together, this study clearly indicates that ALHDL-driven combination therapy of PDT and RNAi is a highly effective modality for inhibition of tumor growth and metastasis.

show abstract

Inhibition of hypoxia-inducible factor 1 with acriflavine sensitizes hypoxic tumor cells to photodynamic therapy with zinc phthalocyanine-encapsulating cationic liposomes

Cited by 89 publications

References 70 publications

The HIF-1 antagonist acriflavine: visualization in retina and suppression of ocular neovascularization

The HIF-1 antagonist acriflavine: visualization in retina and suppression of ocular neovascularization

Multi-OMIC profiling of survival and metabolic signaling networks in cells subjected to photodynamic therapy

An Alternating Irradiation Strategy‐Driven Combination Therapy of PDT and RNAi for Highly Efficient Inhibition of Tumor Growth and Metastasis

Contact Info

Product

Resources

About