HepG2 cells (HCC), characterized by epithelial-like morphology, high proliferation rates, and nontumorigenicity, require cost-effective and efficient treatment. Silymarin, a flavonoid extract of Silybum marianum, is effective in the treatment of HCC. Here, we have reported a comparative anticancer study of the well-characterized nanoformulations of lactobionic acid-adorned porous PLGAencapsulated silymarin (LA-PLGA-Sil) with only porous PLGA-encapsulated silymarin (PLGA-Sil) against HepG2 cells. Treatment of HepG2 cells with LA-PLGA-Sil produced a significant deterioration in cell viability at an essentially low dose as compared with PLGA-Sil, due to the adorned lactobionic acid moiety, which results in better targeting. p53, a tumor suppressor gene, essentially initiates apoptosis in cells procuring wild-type p53 (p53 +/+). In our report, treatment of HepG2 cells (p53 +/+) with LA-PLGA-Sil activated p53, which in turn inhibited the proliferation of cells by instigating cell-cycle arrest and apoptosis in a concentration-dependent manner and simultaneously stabilized the nuclear translocation of NFκB-p65. To explore the effect of LA-PLGA-Sil on the expression of microRNA, we observed that LA-PLGA-Sil markedly upregulated the miR-29b in human HCC cells. Reactivation of the p53 gene by miR-29b targeted Bcl-2 and triggered the sequential activation of mediators such as proapoptotic Bax protein, release of cytochrome c, and the activation of caspase proteins (caspase-3 and caspase-9). Furthermore, the overexpression of NFκB-p65 in HepG2 cells reversed the repression, and this stabilization effect of LA-PLGA-Sil on the nuclear translocation of p65 led to the significant downregulation of miR-29b and successively decreased the p53 expression in LA-PLGA-Sil-treated cells, thereby providing a survival mechanism to HepG2. In entirety, our study demonstrated the extensive potential of LA-PLGA-Sil to instigate the cell death of HepG2 cells via apoptosis by targeting the miR-29b/p53 axis through the stabilization of NFκB. It also impaired the migratory activity of HepG2 cells and thereby furnished a comprehensive way to HCC therapeutic treatment.
Epidermal growth factor receptor (EGFR) normally over-express in non-small cell lung cancer (NSCLC) and its mutations act as oncogenic drivers in the cellular signal transduction pathway and induce downstream activation...
Till date most of the accessible therapeutic options are virtually non-responsive towards Triple-negative breast cancer (TNBC) due to their highly aggressive and metastatic nature. Interestingly, chemotherapy reacts soundly in many...
BackgroundCancer continues to threat the mortal alongside scientific community with its burgeoning grasp. Although efforts have been directed to tame cancer by radiotherapy, photodynamic therapy, chemotherapy it came at a cost of fatal side effects.PurposePlant derived bioactive compounds carries an inevitable advantage of being safer, bioavailable & less toxic compared to contemporary chemotherapeutics. This study analyzed anti-cancerous potential of volatile oil, extracted fromNigella sativa, in-vitro against MDA-MB-231, MCF-7 & in-vivo on tumor growth in mice after successful oral administration.Study DesignOur strategic approach employed solvent extraction of black seed oil (BSO) to highlight orchestrated use of its potent integrants - TQ, Carvacrol & TA which in modest amounts show anti-cancerous properties compared to their individual treatment.We attempted to show this cost effective, safe & bioavailable form of dealing with the atrocities of breast cancer by means of MTT, Apoptotic, Western Blot Assays besides Transwell & Wound healing Assay. Reduction in the solid tumour in-vivo & near normalcy restoration of tissue section architecture from the BSO treated tumour sets are indicative of the better anti-tumorigenic potential of BSO.MethodsBSO’s Solvent extraction was performed followed by its characterization. MTT aided cytotoxicity study of BSO alongside major components in PBMC & cancer cells while its efficacy was presented by flow cytometric ROS analysis, cell cycle arrest & apoptosis assessment. Anti-migratory potential evaluated by Wound Healing, Transwell Migration & Western Blot while the expression study of a wide range of proteins, miRNAs & the in-vivo studies undertaken climaxed the confirmation of the anti-cancerous potential of BSO.ResultsComparatively reduced concentrations of TQ, TA & Carvacrol in BSO played a synergistic role to enhance apoptotic potential via Caspase 7 & 9, through enhanced ROS & expression of apoptotic family of proteins, miRNAs besides uplifting the anti-migratory perspective by effectively enhancing E-cad & downregulating lamellipodia, filopodia assembly & MMPs in MCF-7 & MDA-MB-231. Similar observations in-vivo outlined the therapeutic potential of BSO.ConclusionThis study culminates isolation & processing of BSO in a simplified procedure, thereby aiming at a more lucrative paradigm to be accepted in contemporary phytomedicine research.
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