Photodynamic Efficacy of Cercosporin in 3D Tumor Cell Cultures.

Mantas Grigalavicius,Maria Mastrangelopoulou,Delmon Arous,Asta Juzeniene,Mathilde Ménard,Kristian Berg,Theodossis A Theodossiou,Ellen Skarpen

doi:10.1111/php.13257

Mantas Grigalavicius, Maria Mastrangelopoulou + Show 6 more

Open Access

https://doi.org/10.1111/php.13257

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Abstract

In the present work, we study the photodynamic action of cercosporin (cerco), a naturally occurring photosensitizer, on human cancer multicellular spheroids. U87 spheroids exhibit double the uptake of cerco than T47D and T98G spheroids as shown by flow cytometry on the single cell level. Moreover, cerco is efficiently internalized by cells throughout the spheroid as shown by confocal microscopy, for all three cell lines. Despite their higher cerco uptake, U87 spheroids show the least vulnerability to cerco-PDT, in contrast to the other two cell lines (T47D and T98G). While 300μm diameter spheroids consistently shrink and become necrotic after cerco PDT, bigger spheroids (>500μm) start to regrow following blue-light PDT and exhibit high viability. Cerco-PDT was found to be effective on bigger spheroids reaching 1mm in diameter especially under longer exposure to yellow light (~590nm). In terms of metabolism, T47D and T98G undergo a complete bioenergetic collapse (respiration and glycolysis) as a result of cerco-PDT. U87 spheroids also experienced a respiratory collapse following cerco-PDT, but retained half their glycolytic activity.

Highlights

Photodynamic therapy of cancer (PDT) [1] is cancer treatment modality which utilizes a photoactivatable drug, light of the appropriate wavelength ensuring PS activation, and interstitial molecular oxygen
We found that PDT treatment collapsed the metabolism in MCF7 and U87 cells while T98G cells, despite of their respiratory activity dropping to background levels, retained about 1/3 of their glycolytic activity following cerco-PDT
We evaluated the effect of cerco-PDT in 3D cultures of three mammalian cancer cell lines, namely T47D, U87 and T98G

Summary

Introduction

Photodynamic therapy of cancer (PDT) [1] is cancer treatment modality which utilizes a photoactivatable drug (photosensitizer, PS), light of the appropriate wavelength ensuring PS activation, and interstitial molecular oxygen. PDT can destroy cancer through a combination of [1] cell phototoxicity, [2] vascular shut down leading to tumor starvation and [3] immunogenicity triggered by the primary treatment-induced inflammation. The main restraint of PDT is the limited depth of light penetration into tissue. Light in the red end of the visible spectrum can penetrate a few millimeters (~2 mm) into tissue while in the blue end the corresponding penetration depth is a couple of hundred micrometers (~300 μm at ~450 nm, [1]). An ideal clinical PDT photosensitizer would need to exhibit strong absorbance at or longer than 650 nm (deep red)

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