Curcumin as a safe traditional compound has various benefits such as anticancer activities. However, low solubility in water is a problem. Herein, curcumin encapsulated in polymersome nanoparticles (CPNs) have been developed, the physicochemical properties have been evaluated, and cytotoxicity effects on HT29 cells were evaluated by MTT assay and annexin V/PI staining. The expression of stemness markers including CD44, CD133, and CD24, as well as miRNAs (miR‐126, miR‐34a, miR‐21, miR‐155, miR‐221, and miR‐222) and some potential targets, was evaluated in CPNs‐treated and untreated cells. Physicochemical analysis confirmed the encapsulation of curcumin in polymersomes and showed a spherical shape, an appropriate mean size of 259.5±1.5 nm, the acceptable polydispersity index of ~ 0.465, and the zeta potential of (‐8.74±0.2), as well as long‐term storage of CPNs at 4°C. According to the result, CPNs with the IC50 of 14 μg/ml increased apoptosis and induced S arrest in treated cells. Flow cytometry analysis showed the decrease in cancer stemness markers. RT‐qPCR analysis identified the downregulation of miR‐21, miR‐155, and miR‐221/222, as well as upregulation of miR‐34a, miR‐126, and deregulation of some apoptotic targets such as P53, CASP9, CASP8, CASP3, BAX, and BCl‐2 in CPNs‐treated cells. As a result, CPNs can be a safe and effective complementary agent to diminish cancer stem cells and tumor recurrence in colorectal cancer therapy.
Curcumin is an anti‐cancerous agent, but its low‐solubility limits its clinical use. The relationship between deregulation of miRNAs and their targets suggested that miRNAs can be interest targets of curcumin in treatment of different cancers. In this study, to overcome essential defects of the clinical usage of this golden drug, curcumin‐encapsulated polymersome nanoparticles (CPNs) have been developed, and the cytotoxicity effects were studied on MDA‐MB‐231 breast cancer cells. The expression level of miR‐182/125b and the expression pattern of some potential targets in apoptotic pathway, predicted by in silico approaches, were analyzed by RT‐qPCR in CPNs‐treated and untreated cells. Moreover, the amount of CASP9 and CASP8 proteins were determined by Western blotting. The effect of CPNs on cell migration were studied by scratch test and the level of EGFR, E‐cadherin, and beta‐catenin proteins were monitored in CPNs‐treated and untreated cells by western blotting. RT‐qPCR analysis identified the downregulation of miR‐125b and miR‐182 in CPNs‐treated cells and the upregulation of some predicted apoptotic target genes such as P53, CASP9 and BAX after 24 hours. Western blotting confirmed the effects of curcumin on the increase of cleaved CASP9 protein. Based on data from the current experiment, the migration of MDA‐MB‐231 cells was decreased after CPNs treatment. According to the results, CPNs, as suitable and compatible nanocarriers, can deliver curcumin into cancerous cells more effectively and can increase the therapeutic effects of curcumin on MDA‐MB‐231 cells partly by suppression of miR‐125b and miR‐182 as well as induction of apoptosis and inhibition of metastatic progression.
The most serious hallmark step of carcinogenesis is oxidative stress, which induces cell DNA damage. Although in normal conditions ROS are important second messengers, in pathological conditions such as cancer, due to imbalanced redox enzyme expression, oxidative stress can occur. Recent studies with firmly established evidence suggest an interdependence between oxidative stress and thyroid cancer based on thyroid hormone synthesis. Indeed, a reduced antioxidant defense system might play a part in several steps of progression in thyroid cancer. Based on studies that have been conducted previously, future drug designs for targeting enzymatic ROS sources, as a single agent or in combination, have to be tested. Polyphenols represent the potential for modulating biological events in thyroid cancer, including antioxidative activity. Targeting enzymatic ROS sources, without affecting the physiological redox state, might be an important purpose. As regards the underlying chemopreventive mechanisms of natural compounds that have been discussed in other cancer models, the confirmation of the influence of polyphenols on thyroid cancer is inconclusive and rarely available. Therefore, there is a need for further scientific investigations into the features of the antioxidative effects of polyphenols on thyroid cancer. The current review illustrates the association between some polyphenols and the key enzymes that take place in oxidation reactions in developing thyroid cancer cells. This review gives the main points of the enzymatic ROS sources act and redox signaling in normal physiological or pathological contexts and supplies a survey of the currently available modulators of TPO, LOX, NOX, DUOX, Nrf2, and LPO derived from polyphenols.
Colorectal Cancer (CRC) has the most common malignant gastrointestinal cancer which representing about13% of all malignant tumor. CRC Cancer Stem Cell is the major reasons for recurrence of disease cause of solid tumor metastasis, relapse of cancer after treatment and drug resistance. Silibinin, an herbal extract from milk thistle plant, has been identified as a potential cancer medicine that can target the signaling pathway of CSCs and change their abilities. In our study, the results of CSC confirmation test such as specific surface CD markers and ability to form colonospheres was indicated the HT-29 cells as CSC-CRC. To increase the effectiveness of Silibinin, and also, to evaluate therapeutic intentions on HT-29 cancer stem-like cells, we encapsulated Silibinin in polymersome nanoparticle and validated the anti-proliferative and apoptotic activities of this new patent by MTT assay, AnnexinV/PI method, cell cycle analysis and DAPI staining. Furthermore, the efficacy of drug on Multicellular Tumor Spheroid (MCTS) and single cell suspension was showed that SPN had succeed to decrees the expression level of CSC CD markers compared with control group. Follow by using miRNAs as a novel and minus invasive expertise for prognostic, RT-qPCR confirmed that SPNs can repress oncogenic miRNAs such as miR-221 and miR-222. Silibinin encapsulated in Polymersome Nanoparticles (SPNs) can also enhance the expression of tumor suppressor miR-34a and some of its proapoptotic target genes such as P53, BAX, CASP9, CASP3, and CASP8. Our results suggested that SPNs can be recognized as a new stimulant factor to direct the HT-29 cancer cells toward apoptosis pathways thorough modify expression of some miRNAs and their apoptotic target genes directly and/or indirectly.
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