Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening.
Level 5 - mechanism / opinion, no new human data
In vitro bench research using cell lines (no human data).
PubMed 36982675 · doi:10.3390/ijms24065602
What was done
The authors evaluated the cytotoxic and phototoxic potential of nine DNA-intercalating compounds: dyes (methylene blue [MB], acridine orange [AO], gentian violet [GV]), natural products (curcumin [CUR], quercetin [QT], epigallocatechin gallate [EGCG]), and chelating compounds (neocuproine [NEO], 1,10-phenanthroline [PHE], 2,2'-bipyridyl [BIPY]). Cytotoxicity was assessed in vitro using non-cancer keratinocytes (HaCaT) and squamous cell carcinoma (MET1) cells. Phototoxicity assays and intracellular ROS detection were conducted in MET1 cells following irradiation (640 nm for MB, 457 nm for AO) and further evaluated in WM983b melanoma cells.
What was found
In MET1 cells, IC50 values were <30 µM for the dyes and curcumin, but >100 µM for QT, EGCG, BIPY, and PHE. Light irradiation at 640 nm (MB) and 457 nm (AO) decreased their IC50 values. Intracellular ROS generation was most pronounced in MET1 cells treated with AO at low concentrations. WM983b melanoma cells were more resistant, showing slightly higher IC50 values for MB and AO. Exact numerical IC50 values and confidence intervals were not reported in the abstract.
Why it matters
The study identifies acridine orange as a potent photosensitizer candidate capable of generating reactive oxygen species at low concentrations under moderate light doses in preclinical skin cancer cell models.
Limits
The study is restricted entirely to in vitro cell cultures without in vivo validation of safety, depth of light penetration, or pharmacokinetics. Exact quantitative IC50 values and measures of statistical variance were omitted from the abstract.
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