ABSTRACT
Curcumin is an antiproliferative phytochemical extracted from Curcuma longa L and which has been studied in preclinical drug screening using cell monolayers and animal models. However, several limitations of these culture systems may be overcome by performing screening with three-dimensional (3-D) cell culture. The aim of this study was to investigate the effects of curcumin on cytotoxicity and genotoxicity as well as spheroid growth using cervical adenocarcinoma HeLa cell spheroids by performing RT-PCR mRNA expression of genes involved in cell death (CASP3, CASP8, CASP9, PARP1, BBC3, BIRC5, BCL2, TNF), autophagy (BECN1, SQSTM1), cell cycle regulation (TP53, C-MYC, NF-kB, CDKN1A, m-TOR, TRAF-2), DNA damage repair (H2AFX, GADD45A, GADD45G), oxidative stress (GPX1), reticulum stress (EIF2AK3, ERN1), and invasion (MMP1, MMP9) was investigated. Curcumin was cytotoxic in a concentration-dependent manner. Curcumin-treated spheroids exhibited lower proliferative recovery and cell proliferation attenuation, as observed in the clonogenic assay. Further, no marked genotoxicity was detected. Curcumin-treated spheroids displayed reduced expression of BECN1 (2.9×), CASP9 (2.1×), and PARP1 (2.1×) mRNA. PARP1 inhibition suggested disruption of essential pathways of proliferation maintenance. Downregulated expression of CASP9 mRNA and unchanged expression of CASP3/8 mRNA suggested caspase-independent cell death, whereas downregulated expression of BECN1 mRNA indicated autophagic disruption. Therefore, curcumin exhibits the potential for drug development with antiproliferative activity to be considered for use in cancers.
Subject(s)
Curcumin , Animals , Humans , Curcumin/pharmacology , Caspase 3 , HeLa Cells , Caspases , Cell ProliferationABSTRACT
Uterine intussusception is a rare condition in bitches. This study aimed to report an unusual case of prolapsed uterine intussusception in a female dog. A 2-year-old American Bully bitch was received with labor history of large fetus requiring manual traction. The animal presented mucosal prolapse through the vulva, unproductive contractions and abdominal discomfort. After partial correction of mucosal prolapse, the dog was referred to ovary-hysterectomy surgery to correct prolapsed mucosa. During the surgical procedure, surgeons observed that the uterine horns were invaginated into the uterine body, rotated, and the tissue was slightly devitalized and congested. As previously described, this condition occurred during the immediate postpartum period. Thus, we suggest that this period can be a facilitator for the establishment of uterine intussusception.(AU)
A intussuscepção uterina é uma condição rara em cadelas. Portanto, este estudo tem por objetivo relatar um caso incomum de intussuscepção uterina prolapsada em fêmea canina. Uma cadela American Bully de dois anos de idade com histórico de parto de feto absoluto grande no qual necessitou de auxílio por tração manual foi apresentada. O animal exibiu um prolapso de mucosa através da vulva, contrações improdutivas e dores abdominais. Após a retração parcial do prolapso de mucosa, a cadela foi encaminhada para a ovário-histerectomia que teve por objetivo, também, corrigir a mucosa prolapsada. Durante o procedimento cirúrgico, foram verificados os cornos uterinos invaginados no corpo uterino, rotacionados, com o tecido levemente desvitalizado e congesto. Assim, como poucos casos encontrados na literatura, esta condição ocorreu durante o puerpério imediato. Dessa forma, sugere-se que este período, embora não seja um fator determinante para o estabelecimento da intussuscepção uterina, pode ser um facilitador no estabelecimento dessa condição.(AU)
