Selective photodynamic effects on cervical adenocarcinoma cells provided by F127 Pluronic®-based micelles modulating hypericin delivery

Abstract Cervical cancer is a leading cause of death among women. The endocervical adenocarcinoma (ECA) represents an aggressive and metastatic type of cancer with no effective treatment options currently available. We evaluated the antitumoral and anti-migratory effects of hypericin (HYP) encapsulated on Pluronic F127 (F127/HYP) photodynamic therapy (PDT) against a human cell line derived from invasive cervical adenocarcinoma (HeLa) compared to a human epithelial cell line (HaCaT). The phototoxicity and cytotoxicity of F127/HYP were evaluated by the following assays: colorimetric assay, MTT, cellular morphological changes by microscopy and long-term cytotoxicity by clonogenic assay. In addition, we performed fluorescence microscopy to analyze cell uptake and subcellular distribution of F127/HYP, cell death pathway and reactive oxygen species (ROS) production. The PDT mechanism was determined with sodium azide and D-mannitol and cell migration by wound-healing assay. The treatment with F127/HYP promoted a phototoxic result in the HeLa cells in a dose-dependent and selective form. Internalization of F127/HYP was observed mainly in the mitochondria, causing cell death by necrosis and ROS production especially by the type II PDT mechanism. Furthermore, F127/HYP reduced the long-term proliferation and migration capacity of HeLa cells. Overall, our results indicate a potentially application of F127/HYP micelles as a novel approach for PDT with HYP delivery to more specifically treat ECA.

Effects of depomedroxyprogesterone acetate on the development and maintenance of Candida albicans in the vagina of oophorectomized Wistar rats (Rattus norvegicus) / Efeitos do acetato de depomedroxyprogesterone sobre o desenvolvimento e manutenção de Candida albicans na vagina de ooforectomizado ratos Wistar ( Rattus norvegicus )

The objective of this study was to determine the effect of medroxyprogesterone acetate (DMPA) on the development and maintenance of Candida albicans in the vagina of oophorectomized Wistar rats. The animals were divided into negative control groups (NCG), which received injections of sterile saline; positive control groups (PCG), which were given injections of estradiol valerate; and progesterone groups (PG), which were given injections of Depo-Provera®. After one week of hormonal induction, vaginal infection by C. albicans was induced in all the groups and detected by vaginal yeast culture and Papanicolaou smear. In addition, scanning and transmission electron microscopy images were obtained to confirm the vaginal infection by yeast in PG. A difference in progesterone levels in PG was observed between the basal level and after hormonal induction (P<0.0001). In this group, 100 percent of the rats acquired vaginal infection in the first week, but did not maintain it until the third week. The pharmaceutical brand of DMPA was effective for inducing the metestrus or diestrus phase of the estrous cycle in rats, similar to the use of pure progesterone. In contrast to estrogen treatment, progesterone alone could not support an experimental vaginal infection by C. albicans for any significant period of time.

O objetivo do presente estudo foi determinar os efeitos do acetato de depomedroxyprogesterona (ADMP) no desenvolvimento e manutenção de Candida albicans na vagina de ratas Wistar ooferectomizadas. Os animais foram divididos em grupos controle negativos (GCN), que receberam injeções de salina estéril; grupos controle positivos (GCP), que receberam injeções de valerato de estradiol; e grupos progesterona (GP), nos quais foram feitas injeções de Depo-Provera®. Após uma semana da aplicação hormonal, foi induzida a infecção vaginal por C. albicans em todos os grupos, detectada por cultura para leveduras vaginais e esfregaço de Papanicolaou. Foram feitas ainda imagens por microscopia eletrônica de varredura e transmissão para confirmar a infecção pela levedura no GP. Foram observados diferentes níveis de progesterona em GP, entre os valores basais e após a indução hormonal (P<0,0001). Neste grupo, 100,0 por cento das ratas contraíram a infecção vaginal na primeira semana, mas não a mantiveram até a terceira semana. A forma farmacêutica de ADMP foi efetiva em induzir as fases de metaestro e diestro do ciclo estral das ratas, da mesma forma que usando progesterona pura. Em contraste com o que ocorre no tratamento com estrógeno, a progesterona não pôde manter a infecção vaginal experimental por C. albicans por um período significativo de tempo.