Cinnamaldehyde and Hyperthermia Co-Treatment Synergistically Induces ROS-Mediated Apoptosis in ACHN Renal Cell Carcinoma Cells

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.

Inhibiting AGS Cancer Cell Proliferation through the Combined Application of Aucklandiae Radix and Hyperthermia: Investigating the Roles of Heat Shock Proteins and Reactive Oxygen Species

“…This study also sheds light on the downregulation of factors related to metastasis and angiogenesis, such as Cyclin D1, VEGF, and MMP-9, under combined treatment, emphasizing the potential therapeutic promise of this strategy for controlling cancer cell proliferation and metastasis [60][61][62][63]. Importantly, the combined application of AR and 43 • C HT was found to induce cell cycle arrest at the G2/M phase, a process closely associated with the provocation of apoptosis [64,65]. Our findings suggest that the occurrence of apoptosis was dose-dependent under the combined treatment, suggesting the potential for a precise therapeutic approach.…”

In Vitro Effect of Herbal Medicines with Thermal Characteristics on Heat Sensitivity in Cancer Cells

“…Physiological reactions of the body to high-temperature stimulation include alterations in membrane permeability or the cytoskeletal system, macromolecule synthesis or intracellular signaling, and DNA repair inhibition [12,13]. In addition, in vitro studies on the combination of hyperthermia with natural products have demonstrated (A) the efficacy of using compounds produced from nature in conjunction with hyperthermia [10,14]. Therefore, we hypothesized that the combination of herbal medications capable of inducing warm or hot qi and hyperthermia might boost the efficacy of hyperthermia treatment of cancer in vitro.…”

“…To complement these apoptotic qualities, hyperthermia is often combined with other therapeutic procedures like radiation, chemotherapy, surgery, and immunotherapy [9]. Specifically, natural products may significantly improve the outcome of hyperthermia on cancer cells by acting synergistically and with fewer adverse effects, and in addition is inexpensive [10].…”

Enhancing Gastric Cancer Therapeutic Efficacy through Synergistic Cotreatment of Linderae Radix and Hyperthermia in AGS Cells

“…One approach to overcome these limitations is the use of hyperthermia therapy [40]. Cancer hyperthermia therapy involves the use of heat to target and selectively destroy cancer cells [41,42]. However, cancer hyperthermia therapy has limited efficacy when used alone because it induces a heat shock response that activates HSFs and HSPs.…”