Nanolipoparticles-mediated MDR1 siRNA delivery reduces doxorubicin resistance in breast cancer cells and silences MDR1 expression in xenograft model of human breast cancer

Objective(s): P-glycoprotein (P-gp) is an efflux protein, the overexpression of which has been associated with multidrug resistance in various cancers. Although siRNA delivery to reverse P-gp expression may be promising for sensitizing of tumor cells to cytotoxic drugs, the therapeutic use of siRNA requires effective carriers that can deliver siRNA intracellularly with minimal toxicity on target cells. We investigated a special class of PEGylated lipid-based nanoparticles (NP), named nanolipoparticles (NLPs), for siRNA- mediated P-gp downregulation. Materials and Methods: NLPs were prepared based on low detergent dialysis method. After characterization, we evaluated the effect of NLPs on siRNA delivery, and P-gp downregulation compared to oligofectamineTM (OFA) in vitro and in vivo. Results: Our results showed a significant decrease in P-gp expression and subsequent enhancement of chemosensitivity to doxorubicin in vitro. Although the effectiveness of NLPs for in vitro siRNA delivery compared to OFA was limited, the results of in vivo studies showed noticeable effectiveness of NLPs for systemic siRNA delivery. siRNA delivery using NLPs could downregulate MDR1 in tumor cells more than 80%, while OFA had a reverse effect on MDR1 expression in vivo. Conclusion: The results indicated that the prepared NLPs could be suitable siRNA delivery systems for tumor therapy

Role of regulatory miRNAs of the PI3K/AKT signaling pathway in the pathogenesis of breast cancer

Breast cancer is one of the most common tumors in women. Current data indicate that the overexpression of some microRNAs (miRNAs) is associated with breast cancer, in relation to stage, tumor size and potential for metastasis. Some studies have reported that miRNAs have critical roles in cellular processes implicated in breast cancer cell growth, migration and metastasis by targeting the PI3K/AKT oncogenic signaling pathway. Therefore, identifying novel regulatory miRNAs for this oncogenic pathway and discovery of their related target genes may represent a promising therapeutic approach for breast cancer therapy. This review highlights the recent findings about the potential role of PI3K/AKT signaling regulatory miRNAs in breast cancer tumorigenesis

Synergistic effects of Ferula gummosa and radiotherapy on induction of cytotoxicity in HeLa cell line

Objective: Cervical cancer is the second most common type of cancer among women, worldwide; and for treatment of this type of cancer radiotherapy is commonly used. Ferula gummosa Boiss(“Barije” in Persian, from the family Apiaceae), (F. gummosa), is an extremely precious medicinal plant which naturally grows throughout the Mediterranean and Central Asia and is a native plant in Iran. The present study examined the cytotoxic effects of F. gummosa in terms of induction of apoptosis and radiosensitivity in HeLa cells. Materials and Methods: In order to determine F. gummosa cytotoxicity in HeLa cells, the cells were incubated with different concentrations of the plant resin(0-1000 µg/ml) for 24, 48 and 72 hr. Cytotoxicity was determined by MTT assay. The role of apoptosis in F. gummosa cytotoxicity was investigated using flow cytometry following propidium iodide (PI) staining of DNA. For radiosensitivity assessment, F. gummosa-treated cells were exposed to 2 Gy γ-rays, and cytotoxicity was determined in irradiated and non-irradiated (control) groups by MTT and the synergism factor was calculated. Results: F. gummosa decreased cell viability in HeLa cells in a concentration- and time-dependent manner. Flow cytometryanalysisindicated that apoptosis is involved in F. gummosa-induced cytotoxicity. Co-administration of F. gummosa and radiotherapy, showed that this plantat non-toxic low doses, could result in almost 5-fold increment in sensitization of cells towards radiation-induced toxicity. Conclusion: The concurrent use of F. gummosa and radiation increases radiosensitivity and cell death. Therefore, F. gummosa can be considered as a potential radiosensitizer agent against cervical cancer

An ethnobotanical survey on hormozgan province, Iran

Objective: The present study is based on an ethnobotanical research project conducted in Hormozgan province that is located in south of Iran, bordering waters of the Persian Gulf and Oman Sea. This survey was carried out in order to recover the ethnobotanical and ethnomedicinal knowledge of the residents of this province. They are using medicinal and functional plants for treating or preventing several diseases. Materials and Methods: Ethnobotanical data sheets were run with the native inhabitants and people of the province by arranging frequent field trips to different parts of the province and direct interviews with them especially those who were more familiar with the plants and their usage.Results: A total of 150 plant species belonging to 53 families were recorded for their ethnobotanical and ethnomedicinal uses among the people of province. The records were developed by scientific names, family names, local names, medicinal parts used, different ways of their application, and traditional uses of the plants. There was high compliance in the use of plants in painful disorders, gastrointestinal, and dermatological diseases.Conclusion: This study revealed that the people of Hormozgan province have a rich knowledge of natural resources. The use and consumption of medicinal plants are still important parts of their life. Rational use of native medicinal plants may benefit and improve their living standards and quality of life. The results of this study can be used as a basis for selecting herbs for further pharmacological, phytochemical, and pharmacognostical studies

Nanolipoparticles-mediated MDR1 siRNA delivery: preparation, characterization and cellular uptake

Objective(s): Lipid-based nanoparticles (NLP) are PEGylated carriers composed of lipids and encapsulated nucleic acids with a diameter less than 100 nm. The presence of PEG in the NLP formulation improves the particle pharmacokinetic behavior. The purpose of this study was to prepare and characterize NLPs containing MDR1 siRNA and evaluate their cytotoxicity and cellular uptake. MDR1 siRNA could be used in multidrug resistance reversal in cancer therapy. Materials and Methods: siRNAs were encapsulated into NLPs consisted of mPEG-DSPE/DOTAP/DOPE (10:50:40 molar ratio) by the detergent dialysis method. The particle diameters of NLPs and their surface charge were measured using dynamic light scattering. siRNA encapsulation efficiency was determined by an indirect method via filtration and free siRNA concentration determination. NLPs cytotoxicity was investigated by MTT assay. The ability of NLPs for siRNA delivery checked in two human cell lines (MCF-7/ADR and EPP85-181/RDB) by fluorescence microscopy and compared with oligofectamine. Results: NLPs containing MDR1 siRNA were prepared with the stable size of 80-90 nm and the zeta potential near to neutral. The siRNA encapsulation efficacy was more than 80%. These properties are suitable for in vivo siRNA delivery. NLPs cytotoxicity studies demonstrated they were non-toxic at the doses used. NLPs improved siRNA localization in both cell lines. Conclusion: NLPs containing MDR1 siRNA can be a good candidate for in vivo siRNA delivery studies