Melanoma is the leading cause of skin cancer deaths, and the poor prognosis of metastatic melanoma has made needs for a novel pharmacological treatment or efficient intervention. Carnosol, a major polyphenolic compound from Rosmarinus officinalis, has a wide range of biological activities including anti-cancer effect. However, the underlying molecular mechanisms of its anti-cancer effect remain poorly understood in malignant human melanoma cells. In the present study, we investigate the apoptotic effect and the underlying anti-cancer mechanisms of carnosol. Our results revealed that carnosol strongly induced apoptosis against human melanoma G361 cells in a dose-and timedependent manner, and caused dramatical elevation in cellular reactive oxygen species (ROS) level during apoptosis. In mechanistic studies, carnosol treatment decreased protein level of anti-apoptotic B-cell lymphoma 2 (Bcl-2) and B cell lymphoma-extra large (Bcl-xL), however, increased level of pro-apoptotic Bcl-2-associated X protein (Bax) protein. Moreover, carnosol escalated cellular level of p53, which was accompanied by a decline of mouse double minute 2 homolog (MDM2) level. Also, carnosol inhibited activation of Src and signal transducer and activator of transcription 3 (STAT3), therefore down-regulated STAT3-dependent gene expression, such as D-series cyclin and survivin. These changes by carnosol were attenuated by pre-treatment of N-acetyl cysteine, and abolished progression of carnosolinduced apoptosis. In conclusion, carnosol induced apoptosis in human melanoma G361 cells through ROS generation and inhibition of STAT3-mediated pathway. Our results provide molecular bases of carnosol-induced apoptosis, and suggest a novel candidate for human melanoma treatment.
Purpose: This study aimed to propose an effective model for the development of an infertility counseling system.Methods: We reviewed the infertility counseling system in Japan, Germany, the United States, the United Kingdom, and Australia. Additionally, we conducted a Focus Group Interview (FGI) with infertility experts and gathered their opinions about a potential counseling system tailored to the needs of infertile women and suitable for Korean context.Results: Based on the literature review and FGI, the proposed infertility counseling system aimed to promote the infertility treatment process; to build a user-friendly system, including financial support for infertility counseling; to incorporate the integrated model of providing medical information and psychological support for infertile women; and to develop a stepped care system. Additionally, the present findings revealed that, to promote infertility counseling, it is necessary to establish a central infertility counseling center that would be responsible for comprehensive planning, implementation, evaluation, research, and supervision of each counseling organization.Conclusion: The results of this study can be used as a basis for proposing a preliminary model for the development of an infertility counseling system in Korea.
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