Abstract

Renal cell carcinoma (RCC) represents the most common form of kidney cancer, which accounts for 3–5% newly diagnosed cancer cases. Since limited therapies are available for RCC, a search for new options is required. Therefore, in this study, we evaluated the combination effect of cinnamaldehyde (CNM) and hyperthermia treatment. CNM treatment combined with 43 °C hyperthermia synergistically increased cytotoxicity in RCC cell line ACHN cells. Through Western blot assays, we observed increased apoptosis signaling and decreased proliferation/metastasis signaling, along with a repressed heat shock protein 70 level. In flow cytometry analyses, CNM and hyperthermia combination clearly induced apoptosis and mitochondrial potential of ACHN cells, while arresting the cell cycle. Investigation of reactive oxygen species (ROS) suggested a significant increase of ROS generation by CNM and 43 °C hyperthermia co-treatment. We could verify that ROS is crucial in the apoptotic action of combination treatment with CNM and hyperthermia through further experiments regarding an ROS scavenger. Overall, we suggest CNM and hyperthermia combination treatment as an alternative option of anticancer strategies for RCC.

Highlights

  • Kidney cancer is the 6th most frequently diagnosed cancer in men and the 10th in women, accounting for 5% and 3% of newly diagnosed cancer cases in 2018 worldwide [1]

  • The renal adenocarcinoma cell line ACHN cells were obtained from the Korean Cell Line Bank (Seoul, Korea) and maintained in Dulbecco’s Modified Eagle Medium (DMEM) medium supplemented with 10% fetal bovine serum (FBS) (Gibco, Grand Island, NY, USA) and 1% penicillin-strep (Gibco, Grand Island, NY, USA) at 37 ◦ C in an incubator with humidified air with 5% CO2

  • Co-treatment with hyperthermia of 43 ◦ C showed dramatically inhibited cell proliferation compared to 37 ◦ C, especially when combined with 90 μM of CNM

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Summary

Introduction

Kidney cancer is the 6th most frequently diagnosed cancer in men and the 10th in women, accounting for 5% and 3% of newly diagnosed cancer cases in 2018 worldwide [1]. Clear cell renal cell carcinoma (RCC) represents the most common form of kidney cancer, which makes up approximately. 80% of the total [2]. An increase of RCC incidence has been observed, probably due to improved early. Biomedicines 2020, 8, 357 detection techniques; the 5-year survival rate has increased during the past 30 years. In the USA, 5-year relative survival rates increased from 50% in 1975–1977 to 74% in 2007–2013 [1]. According to the World Health Organization, more than 14,000 deaths per year result from RCC, ranking as the 13th cause of death from cancer, as approximately 17%

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