MEK5/ERK5 activation regulates colon cancer stem-like cell properties.

Colon cancer has been proposed to be sustained by a small subpopulation of stem-like cells with unique properties allowing them to survive conventional therapies and drive tumor recurrence. Identification of targetable signaling pathways contributing to malignant stem-like cell maintenance may therefore translate into new therapeutic strategies to overcome drug resistance. Here we demonstrated that MEK5/ERK5 signaling activation is associated with stem-like malignant phenotypes.

In Silico HCT116 Human Colon Cancer Cell-Based Models En Route to the Discovery of Lead-Like Anticancer Drugs.

To discover new inhibitors against the human colon carcinoma HCT116 cell line, two quantitative structure⁻activity relationship (QSAR) studies using molecular and nuclear magnetic resonance (NMR) descriptors were developed through exploration of machine learning techniques and using the value of half maximal inhibitory concentration (IC). In the first approach, A, regression models were developed using a total of 7339 molecules that were extracted from the ChEMBL and ZINC databases and recent literature. The performance of the regression models was successfully evaluated by internal and external validations, the best model achieved R² of 0.

Convergence of miR-143 overexpression, oxidative stress and cell death in HCT116 human colon cancer cells.

MicroRNAs (miRNAs) regulate a wide variety of biological processes, including tumourigenesis. Altered miRNA expression is associated with deregulation of signalling pathways, which in turn cause abnormal cell growth and de-differentiation, contributing to cancer. miR-143 and miR-145 are anti-tumourigenic and influence the sensitivity of tumour cells to chemotherapy and targeted therapy.

Vobasinyl-Iboga Alkaloids from Tabernaemontana elegans: Cell Cycle Arrest and Apoptosis-Inducing Activity in HCT116 Colon Cancer Cells.

Phytochemical investigation of the roots of the African medicinal plant Tabernaemontana elegans led to the isolation of three new (1-3) and two known (4 and 5) bisindole alkaloids of the vobasinyl-iboga type. The structures of 1-3 were assigned by spectroscopic methods, mainly using 1D and 2D NMR experiments. All of the isolated compounds were evaluated for their cytotoxicity against HCT116 colon and HepG2 liver carcinoma cells by the MTS metabolism assay.

The Madeira Archipelago As a Significant Source of Marine-Derived Actinomycete Diversity with Anticancer and Antimicrobial Potential.

Marine-derived actinomycetes have demonstrated an ability to produce novel compounds with medically relevant biological activity. Studying the diversity and biogeographical patterns of marine actinomycetes offers an opportunity to identify genera that are under environmental pressures, which may drive adaptations that yield specific biosynthetic capabilities. The present study describes research efforts to explore regions of the Atlantic Ocean, specifically around the Madeira Archipelago, where knowledge of the indigenous actinomycete diversity is scarce.

(3'R)-hydroxytabernaelegantine C: A bisindole alkaloid with potent apoptosis inducing activity in colon (HCT116, SW620) and liver (HepG2) cancer cells.

Ethnopharmacological Relevance: Tabernaemontana elegans Stapf. (Apocynaceae) is a medicinal plant traditionally used in African countries to treat cancer.

Aims Of The Study: To discover new apoptosis inducing lead compounds from T.

MEK5/ERK5 signaling inhibition increases colon cancer cell sensitivity to 5-fluorouracil through a p53-dependent mechanism.

The MEK5/ERK5 signaling pathway is emerging as an important contributor to colon cancer onset, progression and metastasis; however, its relevance to chemotherapy resistance remains unknown. Here, we evaluated the impact of the MEK5/ERK5 cascade in colon cancer cell sensitivity to 5-fluorouracil (5-FU). Increased ERK5 expression was correlated with poor overall survival in colon cancer patients.

miR-143 or miR-145 overexpression increases cetuximab-mediated antibody-dependent cellular cytotoxicity in human colon cancer cells.

miR-143 and miR-145 are downregulated in colon cancer. Here, we tested the effect of restoring these miRNAs on sensitization to cetuximab in mutant KRAS (HCT116 and SW480) and wild-type KRAS (SW48) colon cancer cells. We evaluated cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) and the modulation of signaling pathways involved in immune effector cell-mediated elimination of cancer cells.

Monoterpene indole alkaloid hydrazone derivatives with apoptosis inducing activity in human HCT116 colon and HepG2 liver carcinoma cells.

The derivatization of dregamine (1) and tabernaemontanine (2), two epimeric monoterpene indole alkaloids isolated from the methanol extract of the roots of Tabernaemontana elegans, with several hydrazines and hydroxylamine gave rise to ten new derivatives (3-12). Their structures were assigned by spectroscopic methods, including 2D NMR experiments. The compounds were tested for their ability to induce apoptosis in HCT116 colon and HepG2 liver cancer cells.

Efficient recovery of proteins from multiple source samples after TRIzol(®) or TRIzol(®)LS RNA extraction and long-term storage.

Background: Simultaneous isolation of nucleic acids and proteins from a single biological sample facilitates meaningful data interpretation and reduces time, cost and sampling errors. This is particularly relevant for rare human and animal specimens, often scarce, and/or irreplaceable. TRIzol(®) and TRIzol(®)LS are suitable for simultaneous isolation of RNA, DNA and proteins from the same biological sample.

miR-143 overexpression impairs growth of human colon carcinoma xenografts in mice with induction of apoptosis and inhibition of proliferation.

Background: MicroRNAs (miRNAs) are aberrantly expressed in human cancer and involved in the (dys)regulation of cell survival, proliferation, differentiation and death. Specifically, miRNA-143 (miR-143) is down-regulated in human colon cancer. In the present study, we evaluated the role of miR-143 overexpression on the growth of human colon carcinoma cells xenografted in nude mice (immunodeficient mouse strain: N: NIH(s) II-nu/nu).