Photocatalytic interaction of aminophylline–riboflavin leads to ROS‐mediated DNA damage and cell death: A novel phototherapeutic mechanism for cancer

Abstract

The accompanied tissue devastation and systemic toxicity of chemotherapy has shifted the quest for having an effective and palliative cancer therapy towards photodynamic therapy (PDT). Riboflavin (Rf), an essential micronutrient is emerging as a potent tool of PDT, due to its excellent photosensitizing properties. It can be used as an efficient adjuvant for various anticancer drugs. The hemolytic and proteolytic effect of photoilluminated aminophylline (Am), a xanthine derivative, and Rf is well documented in literature. In this study, using human peripheral lymphocytes we have demonstrated the strong pro-oxidant effects of photocatalytic interaction between Am and Rf. The photo degradation kinetics of Am in the presence of Rf was monitored using UV spectroscopy, fluorescence spectroscopy, and Fourier transform infrared spectroscopy. The resultant pro-oxidant action of Am was monitored through various assays like lipid peroxidation, protein carbonylation, and reactive oxygen species (ROS) generation. Furthermore, the cytotoxic potential of this system was studied using comet and MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. Treated lymphocytes were visualized using fluorescence and scanning electron microscopy to further validate apoptosis. ROS scavengers ameliorated the oxidative damage caused by this system suggesting pivotal role of ROS in causing apoptotic cell death. As cancer cells exhibit increased absorption of Rf as well as are very sensitive in any further ROS level increment, this putative pathway can serve as an effective anodyne phototherapeutic strategy for cancer treatment. © 2017 IUBMB Life, 69(8):611-622, 2017.

ROS mediated antibacterial activity of photoilluminated riboflavin: A photodynamic mechanism against nosocomial infections

“…3a) showed significant intracellular ROS generation. Our results are supported by studies from our lab [[33], [34], [35]] and those of others [36,37] that photoactivated riboflavin does produce ROS. Riboflavin absorbs photons from the illuminated light and undergoes intersystem conversion i.e.…”

“…Our results can be correlated with previous findings of antibiotic lethality due to altered redox status [40]. The effect of ROS scavengers on oxidative damage induced by photoilluminated riboflavin generated oxygen radicals has already been explored previously in our lab [34,41] and it has been clearly observed that if any protein/compound/enzyme is added that can quench generated ROS, then the detrimental effect of ROS is inhibited. Therefore, if any ROS quencher will be present in solution the bacterial inactivation will be hindered.…”

Dihydroartemisinin Increases the Sensitivity of Photodynamic Therapy Via NF-κB/HIF-1α/VEGF Pathway in Esophageal Cancer Cell in vitro and in vivo

“…Esophageal cancer has high morbidity and mortality, partly because patients tend to be diagnosed at an advanced stage and with esophageal obstruction, which seriously affects their quality of life. Thankfully, an effective medical treatment, PDT, has been found to relieve the esophageal obstruction by inducing localized tumor destruction via the photochemical generation of cytotoxic singlet oxygen [15][16][17][18][19].…”

Photochemical Modification of the Extracellular Matrix to Alter the Vascular Remodeling Process

“…However, the HUVEC cells seemed to recover over the next 24 h, and cytotoxicity was only observed 72 h post exposure at 200 µg/mL with the 7 J/cm 2 light dose (Table 1). In the presence of 7 J/cm 2 light dose, which represented the minimal light dose the vessel would be exposed to during in vivo treatment [9,18,19], cytotoxic effects were only observed with the highest concentration of the 10-8-10 Dimer (200 µg/mL) at 24, 48 and 72 h post exposure. The dose of 200 µg/mL is about 1000-fold above the dose of 10-8-10 Dimer which is delivered to the vascular tissues during in vivo or in vitro dosing with a 2 mg/mL 10-8-10 Dimer solution [17].…”