Abstract. Millimeter wave (MW) is an electromagnetic wave with a wavelength between 1 and 10 mm and a frequency of 30-300 GHz that causes multiple biological effects and has been used as a major component in physiotherapies for the clinical treatment of various types of diseases including cancers. However, the precise molecular mechanism of the anticancer activity of millimeter wave remains to be elucidated. In the present study, we investigated the cellular effects of the MW in the U-2OS human osteosarcoma cell line. Our results showed that MW induced cell morphological changes and reduced cell viability in a dose-and time-dependent manner suggesting that MW inhibited the growth of U-2OS cells as demonstrated. Hoechst 33258 staining and Annexin V/propidium iodide double staining exhibited the typical nuclear features of apoptosis and increased the proportion of apoptotic Annexin V-positive cells in a dose-dependent manner, respectively. In addition, MW treatment caused loss of plasma membrane asymmetry, release of cytochrome c, collapse of mitochondrial membrane potential, activation of caspase-9 and -3, and increase of the ratio of proapoptotic Bax to anti-apoptotic Bcl-2. Taken together, the results indicate that the U-2OS cell growth inhibitory activity of MW was due to mitochondrial-mediated apoptosis, which may partly explain the anticancer activity of millimeter wave treatment.
IntroductionHuman osteosarcoma (OS) is the most common primary malignant bone tumor, accounting for approximately 20% of all primary sarcomas in bone (1). It occurs predominantly in adolescents and young adults (2). Well-known for its metastasis and high local recurrence rate (3,4), osteosarcoma is a type of cancer whose treatment requires an extensive multimodal approach including surgery, radiotherapy and chemotherapy.Currently, chemotherapeutic regimens for human osteosarcoma treatment use combination of multiple chemotherapeutic agents including high-dose methotrexate (HD-MTX) with leucovorin rescue, doxorubicin (adriamycin), cisplatin, and ifosfamide either with or without etoposide (5). Although new therapies consisting of aggressive adjuvant chemotherapy and wide tumor excision have led to a significant benefit in terms of patients' survival, the frequent acquisition of drug-resistant phenotypes and unwanted side effects are often associated with chemotherapy and remain as serious problems (6). Moreover, many currently used chemo-therapeutic agents for cancer therapy have potent cytotoxic effects in normal cells and may induce DNA mutations that probably lead to secondary cancers (7). Therefore, new therapeutic strategies which can improve the effect of current chemotherapy need to be developed.A millimeter wave (MW) is an electromagnetic wave with a wavelength between 1 and 10 mm and a frequency of 30-300 GHz. Organisms produce coherent oscillations at 0.5x10 10 -3x10 12 during metabolism similar to the frequency of a millimeter wave. Therefore, the energy of a millimeter wave can be absorbed by the organism through resonan...