β-Elemene Promotes Apoptosis Induced by Hyperthermia via Inhibiting HSP70

Thermotherapy has been presented as a promising strategy to be used as an effective nonsurgical technique for colorectal carcinoma. Although this strategy presents several advantages, including low toxicity and high repeatability, thermotherapy often needs to be combined with other therapies because residual tumor cells that survive hyperthermal treatment often lead to relapse. In this study, we evaluated the effects of β-elemene, which has been proven to have the potential to reverse chemotherapy drug resistance, on promoting the antitumor effects of hyperthermia. β-elemene treatment significantly promoted apoptosis after 2 hours of hyperthermia treatment and blocked cell cycle phases at G1/G0. β-elemene also significantly decreased colony formation and tumor formation abilities after hyperthermia treatment. β-elemene treatment significantly decreased HSP70, but not HSP90 or HSP27, induced by hyperthermia treatment without disturbing HSP70 mRNA. It was also found that β-elemene decreased phosphorylated ERK1/2 induced by hyperthermia. Regain of HSP70 reversed β-elemene-mediated apoptosis, indicating that β-elemene may induce apoptosis by decreasing HSP70. Moreover, β-elemene treatment significantly decreased invasion capacity by decreasing the EMT, which was induced by hyperthermia treatment. Taken together, our results offer a potential strategy for CRC therapy via the combination of hyperthermia and β-elemene.