Kenalog modified by ionizing

Kenalog is a synthetic glucocorticoid drug used to treat various cancers including ocular and choroidal melanoma. However, the drug achieves rarely sustainable results for patients. To overcome this difficulty, the structure of Kenalog was altered by ionizing radiation (IR) to develop a more effective anticancer agent for treatment of various skin cancers. The anticancer effect of modified Kenalog (Kenalog‐IR) was assessed in melanoma cancer cells in vitro. The assessment of mitochondrial functions by MTT assay revealed significant inhibition of melanoma cancer cell viability by Kenalog-IR compared to Kenalog. Moreover, Kenalog-IR-induced apoptotic cell death was associated with the intrinsic mitochondrial pathway by triggering the release of intrinsic apoptosis molecules through activation of caspase-related molecules in concentration and time-dependent manners. Furthermore, it was observed that Kenalog-IR-induced apoptosis was associated with the generation of reactive oxygen species (ROS) with increased G2/M cell cycle arrest. Collectively, Kenalog-IR may be a potential suppressor of skin-related cancer in particular melanoma cancer. Introduction Glucocorticoids have been used for the treatment of various disorders including skin-related diseases and cancers (1,2) and in recent years, several trials have been performed to assess their use as adjuvant therapy in various applications (2-4). They have inhibitory effects in choroidal neovascularization and were revealed to be generally effective in providing anti‐inflammatory effects and short‐term relief in mice (5). Kenalog (triamcinolone acetonide), a synthetic glucocorticoid is commonly used to treat various diseases such as ocular and choroidal melanoma (6,7). However, like many other glucocorticoids, treatment with Kenalog aggravates side effects and rarely achieves sustainable results for patients and in cases requiring chronic therapy (8,9). This may be due to the ability of some tissues such as skin cells including melanoma to produce glucocorticoids from cholesterol due to intramolecular rearrangements caused by UV light that may impair the effectiveness of the drug (10,11). In recent years, several approaches have been devised to increase the bioactivity of glucocorticoids to overcome the problems related to low efficacy and increased adverse effects (12). One of the approaches is incrementally modified drugs (IMD) (13). IMD involves the addition of functional groups and/or synthesis of a conventional drug chemically. Using this innovative technology, several modified glucocorticoid drugs, for example nitro-steroids 21-NO-prednisolone and many other NO‐releasing nonsteroidal anti‐inflammatory drugs (NSAIDs), have been demonstrated to have enhanced efficacy (14). However, efforts made thus far in IMD do not cater enough to the use of physical means such as ionizing radiation (IR). With this in mind, the use of ionizing radiation was developed to improve the potency and efficacy of glucocorticoids in cancer treatment. Various studies have reported the use of ionizing radiation to improve the efficacy of glucocorticoids (15). In a previous study, we revealed that rotenone derivatives modified by ionizing radiation had potential anti-carcinogenic activity in hepatic cancer cells (16). The aim of the present study, was to further improve our knowledge on γ-irradiated glucocorticoids as potential anticancer drugs for Kenalog modified by ionizing radiation induces intrinsic apoptosis mediated by elevated levels of reactive oxygen species in melanoma cancer REMIGIUS AMBROSE KAWALA1,2, FATUMA JUMAPILI RAMADHANI1,2, HYO JIN CHOI1, EUN-HEE LEE1, CHUL-HONG PARK1, BYUNG YEOUP CHUNG1 and HYOUNG-WOO BAI1,2 1Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI), Jeongeup-si, Jeollabuk-do 580-185; 2Radiation Biotechnology and Applied Radioisotope Science, University of Science and Technology (UST), Daejeon 34113, Republic of Korea Received June 16, 2018; Accepted December 6, 2018 DOI: 10.3892/or.2018.6940 Correspondence to: Dr Hyoung-Woo Bai, Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI), 29 Geumgu-gil, Jeongeup-si, Jeollabuk-do 580-185,