Synergistic effects of dendrosomal nanocurcumin and oxaliplatin on oncogenic properties of ovarian cancer cell lines by down-expression of MMPs

BACKGROUND: Contrary to the advantageous anticancer activities of curcumin (Cur), limited bioavailability and solubility hindered its efficacy. Here, nontoxic dendrosomal nano carrier with Cur was used to overcome these problems. Despite considerable antitumor properties of Oxaliplatin (Oxa), the limiting factors are drug resistance and adverse side-effects. The hypothesis of this study was to evaluate the possible synergism between dendrosomal nanocurcumin (DNC) and Oxa and these agents showed growth regulatory effects on SKOV3 and OVCAR3 cells. METHODS: and materials In the present study, colony formation, wound healing motility, cell adhesion, transwell invasion and migration assay and cell cycle arrest with or without DNC, Oxa and Combination were defined. In addition to, real time PCR and Western blot were used to analyze AKT, PI3K, PKC, JNK, P38 and MMPs mRNAs and proteins expressions. Docking of MMP-2-Cur, MMP-2-DNC and MMP-2-Oxa was performed and the results of all three complexes were simulated by molecular dynamics. RESULTS: Our findings illustrated that DNC had the greatest effect on cell death as compared to the Cur alone. Moreover, the growth inhibitory effects (such as cell death correlated to apoptosis) were more intense if Oxa was added followed by DNC at 4 h interval. However, insignificant effects were observed upon simultaneous addition of these two agents in both cell lines. Besides, a combination of agents synergistically alters the relative expression of MMP-9. CONCLUSIONS: The docking results showed that His70 and Asp100 may play a key role at the MMP-2 binding site. The matrigel invasion as well as cell viability of ovarian cancer cell lines SKOV3 and OVCAR3 by DNC alone or in combination with Oxa was inhibited significantly. The inhibitory effects of these agents were due to the differential expression levels of MMP 2 and MMP 9 regulated by multiple downstream signaling cascades. From the molecular dynamic simulation studies, it was confirmed that DNC established a strong interaction with MMP-2.

Protective effect of Lepidium sativum seed extract on histopathology and morphology of epididymis in diabetic rat model / Efecto protector de extracto de semilla Lepidium sativum sobre la histopatología y morfología del epidídimo en modelo de rata diabética

Diabetes mellitus is a frequent and serious metabolic illness all over the world and plants have been a desirable source of medicine recently. Diabetes has unpleasant effect on male reproductive system and it may lead to male infertility. It causes erectile dysfunction and reduces ejaculate volume by affecting the health of small blood vessels and the small nerves that control ejaculation and also decreases libido by decreasing testosterone levels. Current study evaluated the possible protective efficiency of Lepidium sativum (Garden cress) seed extract on fasting blood sugar (FBS) and then assessed histopathological change of epididymis in streptozotocine (STZ)-induced diabetic rats. We randomly categorized 50 adult male Wistar rats into five groups (each 10 rats). Group 1 was control placebo group receiving only 0.1 ml normal saline via gastric gavages, Group 2 as control diabetic rats received an intraperitoneal (IP) injection of STZ 60 mg/kg body weight. Rats with FBS >250 mg/dl were considered as diabetic. Group 3 were diabetic rats receiving insulin in dose 3U/100 g body weight and Groups 4 and 5 were diabetic rats that received 0.1 cc of 200 and 400 mg/kg, ethanol extract of Lepidium sativum seed by gavages daily. One day after the last gavages, rats were anesthetized by chloroform. Epididymis duct was removed from abdomen and weighed with a digital scale. Afterwards, samples were putted in Bouin's solution for histological measurement. Administration of 200 and 400 mg/ml doses of Lepidium sativum seed extract increased epithelium height and decreased interstitial volume density and fibro muscular thickness significantly. Also, volume density of epithelium, fibro muscular, lumen and interstitial decreased significantly. Tubular and lumen diameter did not change significantly in different groups. It appears Lepidium sativum seed extract is a beneficial protective supplementary agent against adverse effects of diabetes on male reproductive system.

La diabetes mellitus es una enfermedad metabólica frecuente y grave que afecta a los hombres en todo el mundo. Recientemente, las plantas han sido una fuente deseable de medicina para este tipo de enfermedad. La diabetes tiene un efecto perjudicial en el sistema reproductivo masculino y puede conducir a la infertilidad. Causa disfunción eréctil y reduce el volumen de la eyaculación al afectar los pequeños vasos sanguíneos y los nervios que controlan la eyaculación. También disminuye la libido reduciendo los niveles de testosterona. El presente estudio evaluó la posible eficacia protectora del extracto de semilla de Lepidium sativum en la glucemia en ayunas y también se evaluó el cambio histopatológico del epidídimo en ratas diabéticas inducidas por estreptozotocina (STZ). Se dividieron aleatoriamente 50 ratas Wistar macho adultas en cinco grupos de 10 ratas cada uno. El grupo 1 recibió 0,1 ml de solución salina normal a través de los gavajes gástricos, el grupo 2 de ratas diabéticas control recibió una inyección intraperitoneal (IP) de STZ 60 mg / kg de peso corporal. Las ratas con FBS> 250 mg / dl se consideraron como diabéticas. El Grupo 3 eran ratas diabéticas que recibieron insulina en dosis de 3 U/ 100 g de peso corporal y los Grupos 4 y 5 estaban compuestos por ratas diabéticas que recibieron 0,1 cc con 200 y 400 mg / kg, de extracto de etanol de semillas de Lepidium sativum por gavajes diarios. Un día después de los últimos gavages, las ratas fueron anestesiadas con cloroformo. Se extrajo el epidídimo y se pesó con una pesa digital. Posteriormente, las muestras se pusieron en solución de Bouin para el estudio histológico. La administración de dosis de 200 y 400 mg / ml de extracto de semilla Lepidium sativum aumentó la altura del epitelio y disminuyó significativamente la densidad volumétrica intersticial y el grosor fibromuscular. Además, la densidad volumétrica del epitelio fibromuscular, lumen e intersticio disminuyeron significativamente. El diámetro tubular y el lumen no cambiaron significativamente en los diferentes grupos. El extracto de semilla de Lepidium sativum es un agente complementario beneficioso protector contra los efectos adversos de la diabetes en el sistema reproductor masculino.