Sunitinib with photoirradiation-mediated reactive oxygen species generation induces apoptosis of renal cell carcinoma cells.

Photodynamic therapy is a clinically approved, minimally invasive,-therapeutic procedure used for the treatment of several cancers. In recent years, sunitinib, one of the tyrosine kinase inhibitors, has also attracted attention as a novel photosensitizer. However, there is currently no data available on the combined cytotoxic effects of sunitinib and photoirradiation on renal cell carcinoma including how the treatment induced cellular toxicity.

In the present study, we used sunitinib as a photosensitizer and evaluated the effects of sunitinib and photodynamic therapy treatment on renal cancer cell lines, including the induction of cell death.

Our study showed that treatment with sunitinib and photoirradiation at 8 mW/cm2 for 30 min resulted in the production intracellular reactive oxygen species (ROS), which is indicated by the increase in mRNA expression levels of PAI-1, NF-κβ, and Caspase-3. An increase in rate of apoptotic reaction and increase in the expression level of apoptotic marker were also observed when cells undergo treatment with sunitinib and photoirradiation.

Our findings suggest that combining photodynamic therapy with sunitinib represents a minimally invasive therapeutic procedure with cancer selectivity for renal cell carcinoma.

Photodiagnosis and photodynamic therapy. 2021 Jun 30 [Epub ahead of print]

Shinkuro Yamamoto, Taku Nakayama, Hitomi Seki, Chiaki Kawada, Hideo Fukuhara, Takashi Karashima, Shun-Ichiro Ogura, Keiji Inoue

Department of Urology, Kochi Medical School, Kohasu, Oko-cho, Nankoku-shi, Kochi, 783-8505, Japan. Electronic address: ., Center for Photodynamic Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku-shi, Kochi, 783-8505, Japan; School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa, 226-8501, Japan. Electronic address: ., Department of Urology, Kochi Medical School, Kohasu, Oko-cho, Nankoku-shi, Kochi, 783-8505, Japan. Electronic address: ., Department of Urology, Kochi Medical School, Kohasu, Oko-cho, Nankoku-shi, Kochi, 783-8505, Japan. Electronic address: ., Department of Urology, Kochi Medical School, Kohasu, Oko-cho, Nankoku-shi, Kochi, 783-8505, Japan; Center for Photodynamic Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku-shi, Kochi, 783-8505, Japan. Electronic address: ., Department of Urology, Kochi Medical School, Kohasu, Oko-cho, Nankoku-shi, Kochi, 783-8505, Japan. Electronic address: ., Center for Photodynamic Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku-shi, Kochi, 783-8505, Japan; School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa, 226-8501, Japan. Electronic address: ., Department of Urology, Kochi Medical School, Kohasu, Oko-cho, Nankoku-shi, Kochi, 783-8505, Japan; Center for Photodynamic Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku-shi, Kochi, 783-8505, Japan. Electronic address: .