Structural alterations in cell organelles induced by photodynamic treatment with chlorin p₆‐histamine conjugate in human oral carcinoma cells probed by 3D fluorescence microscopy

Abstract

We have explored the intracellular cell organelle's structural alterations after photodynamic treatment with chlorin p6‐histamine conjugate (Cp6‐his) in human oral cancer cells. Herein, the cells were treated with Cp6‐his (10 μm) and counterstained with organelle‐specific fluorescence probes to find the site of intracellular localization using confocal microscopy. For photodynamic therapy (PDT), the cells were exposed to ~30 kJ/m2 red light (660 ± 20 nm) to induce ~90% cytotoxicity. We used the three‐dimensional (3D) image reconstruction approach to analyze the photodynamic damage to cell organelles. The result showed that Cp6‐his localized mainly in the endoplasmic reticulum (ER) and lysosomes but not in mitochondria and Golgi apparatus (GA). The 3D model revealed that in necrotic cells, PDT led to extensive fragmentation of ER and fragmentation and swelling of GA as well. Results suggest that the indirect damage to GA occurred due to loss of connection between ER and GA. Moreover, in damaged cells with no sign of necrosis, the perinuclear ER appeared condensed and surrounded by several small clumps at the peripheral region of the cell, and the GA was observed to form a single condensed structure. Since these structural changes were associated with apoptotic cell death, it is suggested that the necrotic and apoptotic death induced by PDT with Cp6‐his is determined by the severity of damage to ER and indirect damage to GA. The results suggest that the indirect damage to cell organelle apart from the sites of photosensitizer localization and the severity of damage at the organelle level contribute significantly to the mode of cell death in PDT.

Progress in the Application of Fluorescent Probes in Oral Tumor Diseases

“…Parihar et al [28] employed fluorescent probes targeted at specific organelles to study the re-infection of oral cancer cells and to monitor the structural changes in organelles triggered by photodynamic therapy (PDT) using a chlorin-p6-histamine conjugate in human oral cancer cells. Their findings suggested that the effectiveness of PDT in inducing apoptosis through various cell death pathways primarily depends on the subcellular localization of the photosensitizer and the extent of damage to organelles.…”

Smart and intelligent optical materials for sensing applications

“…Parihar and Dube [54] explored photodynamic therapy (PDT) using a chlorin p6‐histamine conjugate on the intracellular cell organelle structural alterations in human oral cancer cells. The results of this study indicated indirect damage to cell organelles apart from the sites of photosensitizer localization and led to cell death in PDT.…”

Design, Synthesis, and Biological Evaluation of Novel Quercetin Derivatives as PPAR‐γ Partial Agonists by Modulating Epithelial–Mesenchymal Transition in Lung Cancer Metastasis

“…[ 11,12 ] The application of derivatives that may advocate a strategy to revive the therapeutic condition of cancer treatment via PPAR‐ γ . [ 21 ] Mainly, derivatization of quercetin have drawn increasing interest due to the existence of multiple hydroxyl groups (−OH) that are known to form effective sulfates, methyl ethers, azomethines, and glucuronides compounds. The factors that contribute to its effectiveness includes the presence of 3‐OH which plays a key role in kinase inhibition, [ 22 ] the 7‐OH that leads to weak uncoupling activity, [ 22 ] the 5‐OH is the least reactive one, the carbonyl at 4‐C provides strong intramolecular H‐bonding and the catechol moiety (3’‐OH, 4’‐OH) has redox properties.…”