Assessing the In Vitro Activity of Selected Porphyrins in Human Colorectal Cancer Cells

Abstract

Standard in vitro analyses determining the activity of different compounds included in the chemotherapy of colon cancer are currently insufficient. New ideas, such as photodynamic therapy (PDT), may bring tangible benefits. The aim of this study was to show that the biological activity of selected free-base and manganese (III) metallated porphyrins differs in the limitation of colon cancer cell growth in vitro. White light irradiation was also hypothesized to initiate a photodynamic effect on tested porphyrins. Manganese porphyrin (>1 μM) significantly decreased the viability of the colon tumor and normal colon epithelial cells, both in light/lack of light conditions, while decreasing a free-base porphyrin after only 3 min of white light irradiation. Both porphyrins interacted with cytostatics in an antagonistic manner. The manganese porphyrin mainly induced apoptosis and necrosis in the tumor, and apoptosis in the normal cells, regardless of light exposure conditions. The free-base porphyrin conducted mainly apoptosis and autophagy. Normal and tumor cells released low levels of IL-1β and IL-10. Tumor cells released a low level of IL-6. Light conditions and porphyrins were influenced at the cytokine level. Tested manganese (III) metallated and free-base porphyrins differ in their activity against human colon cancer cells. The first showed no photodynamic, but a toxic activity, whereas the second expressed high photodynamic action. White light use may induce a photodynamic effect associated with porphyrins.

Assessment of chemotherapeutic effects on cancer cells using adhesion noise spectroscopy

“…As opposed to the HT-29 cells, 5-FU did not cause a lowered cell proliferation on HDFs via CAN spectroscopy but remained constant ( Figure 3B ). The shorter doubling time of HT-29 cells ( Forgue-Lafitte et al, 1989 ; Frant et al, 2022 ) compared to HDFs ( Zhu et al, 2004 ; Endt et al, 2010 ; Rorteau et al, 2022 ) may lead to a higher 5-FU-uptake, resulting in stronger proliferation-reducing effects of drug treatment. However, the HDFs’ metabolic activity in the CCK-8 assay in the 5-FU-supplemented medium dropped after 24 h of exposure and stayed constant for the remaining time ( Figure 3B ).…”

Cellular Localization of Selected Porphyrins and Their Effect on the In Vitro Motility of Human Colon Tumors and Normal Cells

“…However, cells absorbed the porphyrin [ 24 ]. Our previous study [ 25 ] indicated that the cytotoxic activity of manganese porphyrin was due to damage to the cell membrane. The evidence suggests that the porphyrin under investigation may not be entering the cell, but instead accumulating within the cell membrane or culture fluid.…”

“…During the incubation of cells with the porphyrins, culture plates were sealed with aluminum foil. Experiments were conducted in two separate conditions: no irradiation (during the entire experiment) and short exposure to white light (3 min) emitted by fluorescent lamps (Osram Lumilux Cool White, Wilmington, MA, USA) with a total power of 90 W and a photon flux density of 120 µmol/m 2 s, according to the method described by Buczek et al [ 59 ] and Frant et al [ 25 ].…”

“…The concentrations of the porphyrins were selected, based on their toxic activity in relation to the tested cells. The toxicity analyses have been described in a previous paper [ 25 ]. After 24 h of cell incubation, MGG staining was performed, and scratch diameter differences were measured.…”

Photodynamic Therapy: From the Basics to the Current Progress of N-Heterocyclic-Bearing Dyes as Effective Photosensitizers

“…According to these studies, coordination with palladium was not as advantageous as with platinum [139], and for porphyrin dyes complexed with copper, nickel, and zinc ions, the copper derivative showed the worst photodynamic effects [140]. In contrast to most research involving metalloporphyrins, Frant et al [142] conclude in their work that manganese-metalized porphyrin is, by itself, cytotoxic, while its free-base analog induces effects only when irradiated on colorectal cancer cells. N-heterocyclic carbene, gold, mesofunctionalized zinc, and palladium coordinated porphyrins prepared by Scoditti et al [143] showed no cumulative impact on the ISC rate, revealing that the introduction of metals at different porphyrin positions does not induce a synergistic effect.…”