beta-elemene and Colorectal-Neoplasms

Topics: AMP-Activated Protein Kinases; Animals; Apoptosis; Autophagy; Cell Line, Tumor; Colorectal Neoplasms; Humans; Mice; Mice, Nude; Reactive Oxygen Species; Sesquiterpenes; TOR Serine-Threonine Kinases

Topics: Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; MicroRNAs; RNA, Long Noncoding; RNA, Messenger; Sesquiterpenes; Transcriptome

The aim of this study is to construct a SYL3C aptamer-anchored microemulsion based on β-elemene and PTX (SYL3C/EP-MEs) for enhancement on colorectal cancer therapy. Such microemulsion is consist of encapsulated drugs (β-elemene and PTX), tumor targeting ligand (3'-end thiolated SYL3C aptamer), thiol conjugated site (maleimide-modified PEGylated 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, mal-DOPE-PEG), pH-sensitive component (DOPE) and other necessary excipients. SYL3C/EP-MEs showed a spherical particle with an average particle size around 30 nm and a high encapsulation efficiency (>80%) for both drugs. β-elemene and PTX could be released controllably from SYL3C/EP-MEs as pH values changed. SYL3C/EP-MEs displayed a selective affinity to HT-29 cells, leading to an obvious increase in cellular uptake, cell apoptosis and cytotoxicity. In the HT-29 tumor xenograft-bearing nude mice model studies, SYL3C/EP-MEs showed an overwhelming tumor growth inhibition, the longest survival time and the lowest systemic toxicity among all the treatments. The potential mechanism of enhanced anti-cancer ability was probably associated with the induction of M1 macrophage polarization, the downregulation of mutant p53 protein and the reduction of bcl-2 protein expression. Collectively, the microemulsion codelivery of β-elemene and PTX using functionalization with SYL3C aptamer provides a novel approach for combinational colorectal cancer-targeted treatment.

Topics: Animals; Antineoplastic Agents; Apoptosis; Aptamers, Nucleotide; Cell Line, Tumor; Colorectal Neoplasms; Drug Carriers; Drug Delivery Systems; Emulsions; HT29 Cells; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Particle Size; Sesquiterpenes; Xenograft Model Antitumor Assays

Colorectal carcinoma is a common malignant tumor occurring in the alimentary system. Despite developments of modern medicine, developed resistance to 5-fluorouracil (5-FU) may lead to poor prognosis. Herein, we aimed to explore the effects of beta-elemene on colorectal carcinoma cells (HCT116 and HT29) as well as the underlying mechanisms. Beta-elemene reduced cell viability and induced apoptosis in HCT116 and HT29 cells. Increased apoptosis following beta-elemene exposure was due to enhanced sensitivity to 5-FU through down-regulating miR-191. Expression of key kinases, including Wnt3a, and β-catenin, were down-regulated by beta-elemene through a miR-191 mechanism. Moreover, beta-elemene might improve resistance of colorectal carcinoma cells to 5-FU by down-regulating miR-191, thereby inhibiting the Wnt/β-catenin pathway.

Topics: beta Catenin; Colorectal Neoplasms; Down-Regulation; Fluorouracil; Gene Expression Regulation, Neoplastic; HCT116 Cells; Humans; MicroRNAs; Neoplasm Proteins; RNA, Neoplasm; Sesquiterpenes; Wnt Signaling Pathway; Wnt3A Protein

Cisplatin-based combination treatment is the most effective systemic chemotherapy for bladder cancer; however, resistance to cisplatin remains a significant problem in the treatment of this disease. β-Elemene is a new natural compound that blocks cell-cycle progression and has a broad spectrum of antitumor activity. This study was conducted to explore the potential of β-elemene as a chemosensitizer for enhancing the therapeutic efficacy and potency of cisplatin in bladder cancer and other solid carcinomas. β-Elemene not only markedly inhibited cell growth and proliferation but also substantially increased cisplatin cytotoxicity towards human bladder cancer 5637 and T-24 cells. Similarly, β-elemene also enhanced cisplatin sensitivity and augmented cisplatin cytotoxicity in small-cell lung cancer and carcinomas of the brain, breast, cervix, ovary, and colorectal tract in vitro, with dose-modifying factors ranging from 5 to 124. β-Elemene-enhanced cisplatin cytotoxicity was associated with increased apoptotic cell death, as determined by DNA fragmentation, and increased activities of caspase-3, -7, -8, -9, and -10 in bladder cancer cell lines. Collectively, these results suggest that β-elemene augments the antitumor activity of cisplatin in human bladder cancer by enhancing the induction of cellular apoptosis via a caspase-dependent mechanism. Cisplatin combined with β-elemene as a chemosensitizer warrants further pre-clinical therapeutic studies and may be useful for the treatment of cisplatin-resistant bladder cancer and other types of carcinomas.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Blotting, Western; Brain Neoplasms; Breast Neoplasms; Caspase 3; Cell Cycle; Cell Proliferation; Cisplatin; Colorectal Neoplasms; Drug Synergism; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lung Neoplasms; Ovarian Neoplasms; Sesquiterpenes; Tumor Cells, Cultured; Urinary Bladder Neoplasms