Photobiomodulation Enhances Cisplatin Cytotoxicity in a Culture Model with Oral Cell Lineages

• Published in: Photochemistry and photobiology 2020-01, Vol.96 (1), p.182-190
• Main Authors: Diniz, Ivana M. A., Souto, Giovanna R., Freitas, Iuri D. P., de Arruda, José Alcides A., da Silva, Janine M., Silva, Tarcília A., Mesquita, Ricardo A.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis; ATP; Cancer; Cell culture; Cell death; Cell Line, Tumor; Cell lineage; Cell viability; Chemotherapy; Cisplatin; Cisplatin - pharmacology; Combined Modality Therapy; Cytotoxicity; Energy metabolism; Humans; Keratinocytes; Light therapy; Low-Level Light Therapy; Mouth Neoplasms - pathology; Necrosis; Sensitivity analysis; Toxicity; Transforming growth factor-b1; Vascular endothelial growth factor
• ISSN: 0031-8655; 1751-1097
• DOI: 10.1111/php.13152

Cisplatin plays a central role in cancer chemotherapy, but resistance to this drug remains a major obstacle in treatment. Drawbacks related to cisplatin failure may be associated with cell energy metabolism. This study investigated whether photobiomodulation (PBM) can potentiate the effects of cisplatin on keratinocytes (HaCat) and cancer cells (SCC25 and HN12). Cells were treated with laser (GaAlAs; 660 nm; 60 mW; 0.33 J; 2.14 W cm−2; 11.7 J cm−2 and 6 s) and cisplatin (7.8 μg mL−1) to evaluate cell viability, Ki‐67, VEGF, TGF‐β1, EGF expression and ROS production. Observations were validated in the SCC25 cell lineage, where the type of cell death (necrosis/apoptosis) and the amount of ATP were assessed. Cell lineages showed increased sensitivity to cisplatin associated with PBM (Cis‐PBM). Ki‐67 was augmented in all cell lineages treated with Cis‐PBM when compared to cisplatin alone (Cis). Cis or Cis‐PBM significantly decreased VEGF expression in cancer cells, while no changes were seen in the expression of TGF‐β1 or EGF compared to control. ROS levels were similar in the Cis and Cis‐PBM groups. Cells treated with Cis‐PBM died by apoptosis, leading to greater consumption of ATP. These observations suggest that PBM may potentiate the effects of cisplatin, leading to increased drug cytotoxicity and enhanced cell death. Drawbacks related to cisplatin failure may be associated with the cell energy metabolism. Photobiomodulation is known to transiently increase ROS production and to promote ATP synthesis. In this study, we investigated whether photobiomodulation can potentiate the effects of cisplatin on keratinocytes and cancer cells. Results suggest that cells treated with cisplatin in combination with photobiomodulation presented more cell cycle arrest and died mostly by apoptosis. Photobiomodulation may potentiate the effects of cisplatin, leading to increased drug cytotoxicity and enhanced cell death.