The anticancer properties of flavokawain b, a kava-kava compound, towards ovarian cancer cells and its antiangiogenic action in vivo and in vitro

• Ano de defesa: 2016
• Autor(a) principal: Mariana Costa Rossette
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Universidade Federal de Minas Gerais
• Palavras-chave em Português: Piper methysticum (Homeopatia)/uso terapêutico; Chalconas/uso terapêutico; Medicina; Neoplasias ovarianas/quimioterapia; Peixe-zebra; Inibidores da angiogênese
• Link de acesso: https://hdl.handle.net/1843/BUOS-AQ3QWJ

Natural products have been utilized for centuries as novel compounds for the treatment and prevention of many diseases. The anticancer potential of chalcones in the Kava-kava extract, a plant grown in the Pacific Islands, have been inferred from the correlation with kava consumption and lower incidence of cancer in these populations. Flavokawain B, a naturally occurring chalcone of kava-kava, has shown impressive anti-cancer effects in several studies, besides other significant anti-inflammatory and antinociceptive activities. Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy and the fifth most common cause of cancer-related deaths in woman. Current treatment with surgery and chemotherapy has improved survival; however recurrence and disease progression occurs in approximately 80% of patients in advanced stage. The development of more effective treatment strategies is urgent and many studies are being done in order to develop target chemotherapeutics against ovarian cancer molecular pathogenesis pathways, such as antiangiogenic drugs, PARP and PI3K inhibitors. In the present work we identified, for the first time, flavokawain B as causing strong antiproliferative and apoptotic effects against ovarian cancer cells with less cytocidal action against normal cells. Flavokawain B results in downregulation of Bcl-2 anti-apoptotic protein expression, increased Bax:Bcl-2 ratio and a significant dose-dependent inhibition of Akt activation on OVCAR-3 cells. These are important findings, since Bcl-2 overexpression and Akt overactivation are frequently associated with poor prognosis and resistance to chemotherapy in ovarian cancer. In addition, this work has demonstrated the strong antiangiogenic action of FKB in vitro and in vivo utilizing a zebrafish model. Altogether, we believe that FKB might be a promising weapon in the arsenal of treatment options against ovarian cancer.