Anticancer Activity and Molecular Mechanism of Resveratrol–Bovine Serum Albumin Nanoparticles on Subcutaneously Implanted Human Primary Ovarian Carcinoma Cells in Nude Mice

Abstract

This study investigates the antitumor effects and functional mechanism of resveratrol-bovine serum albumin nanoparticles (RES-BSANP) on human primary ovarian carcinoma cells in nude mice. An implanted tumor model was established by injecting a suspension of the human primary ovarian cancer cell SKOV 3 into the subcutaneous tissue of nude mice. The tumor-bearing mice (n ¼ 32) were randomly divided into 8 groups, which received intraperitoneal injections of normal saline (0.9%, 0.5 mL), BSA (1.5 mg/kg, 0.5 mL), or RES-BSANP or RES (200, 100, and 50 mg/kg, 0.5 mL), respectively, once a week for 4 weeks. The in vivo antitumor efficacy was evaluated by measurement of tumor volume, whereas morphological alterations were observed by transmission electron microscope (atomic force microscopy); TUNEL assays and immunoblotting for apoptotic and cell proliferation proteins were carried out to elucidate the possible mechanism. RES-BSANP was found to exhibit certain highly desirable characteristics such as innocuity, better dispersity, and water solubility; it affected the in vivo tissue/organ distribution of RES in a remarkable manner. The administration of RES-BSANP significantly retarded the growth of carcinomas in nude mice from the third week onwards, and the inhibition rate was markedly higher than in mice treated with RES (52.43% vs. 46.34%, p < 0.05), without causing weight loss ( p > 0.05). Simultaneously, apoptotic and necrotic morphological characteristics were observed with electron microscopy in the tumor tissues of treated mice. TUNEL staining revealed that the tumors from RES-BSANPtreated mice exhibited a similar apoptotic index as RES control tumors. Western blot analysis of the protein expression profiles revealed that part of the mechanism may be mediated by triggering the release of cytochrome c from the intermembrane space and upregulating the expression of caspase-9 and caspase-3, suggesting that the mitochondrial apoptotic pathway was being activated.

Resveratrol Exerts Differential Effects in Vitro and in Vivo against Ovarian Cancer Cells

“…In another study, resveratrol or resveratrol-bovine serum albumin nanoparticle preparation (50, 100 or 200 mg/ kg; once a week for 4 weeks), administered through i.p. injections beginning on the 7 th day post-implantation, significantly inhibited the growth of xenografted SKOV3 carcinoma in nu/nu mice via apoptosis regulated through the mitochondrial apoptotic pathway (Guo et al, 2010). Although a tumor xenograft model may not be readily interpreted as the true physiologic or clinical condition (Gescher & Steward, 2003;Becher & Holland, 2006;Teicher, 2006), our results may indicate differential response of resveratrol on orthotopic ovarian cancer as compared to xenograft models.…”

Role of membrane dynamics processes and exogenous molecules in cellular resveratrol uptake: Consequences in bioavailability and activities

“…Furthermore, the accumulation of albumin in solid tumours forms the rationale for developing albumin-based drug delivery systems for tumour targeting. Recent studies show antitumour activity of RSV-BSA nanoparticles in different tumour models [81,82]. Albumin nanoparticles constitute a promising drug carrier system for the transport of drugs and for specific target delivery [83][84][85][86].…”

Modulation of inflammatory signaling pathways by phytochemicals in ovarian cancer

“…Resveratrol inhibits proliferation and induces apoptosis in various cancer cell lines, including breast, prostate, colon, and ovarian cancer cells [2]. In nude mice implanted with human ovarian cancer cells, resveratrol suppressed tumor growth when it was administered intraperitoneally, and apoptotic features were observed in the tumor tissues [22,34]. Resveratrol also enhanced the efficacy of cisplatin and doxorubicin in ovarian cancer cells, while reducing the doxorubicin-related cardiac toxicity [51].…”