Therapeutic effects of the euglenoid ichthyotoxin, euglenophycin, in colon cancer

Abstract

Colorectal cancer (CRC) remains one of the most commonly diagnosed cancers and the 3rd leading cause of cancer-related mortality. The emergence of drug resistance poses a major challenge in CRC care or treatment. This can be addressed by determining cancer mechanisms, discovery of druggable targets, and development of new drugs. In search for novel agents, aquatic microorganisms offer a vastly untapped pharmacological source that can be developed for cancer therapeutics. In this study, we characterized the anti-colorectal cancer potential of euglenophycin, a microalgal toxin from Euglena sanguinea. The toxin (49.1-114.6 μM) demonstrated cytotoxic, anti-proliferative, anti-clonogenic, and anti-migration effects against HCT116, HT29, and SW620 CRC cells. We identified G1 cell cycle arrest and cell type - dependent modulation of autophagy as mechanisms of growth inhibition. We validated euglenophycin’s anti-tumorigenic activity in vivo using CRL:Nu(NCr)Foxn1nu athymic nude mouse CRC xenograft models. Intraperitoneal toxin administration (100 mg/kg; 5 days) decreased HCT116 and HT29 xenograft tumor volumes (n=10 each). Tumor inhibition was associated with reduced expression of autophagy negative regulator mechanistic target of rapamycin (mTOR) and decreased trend of serum pro-inflammatory cytokines. Together, these results provide compelling evidence that euglenophycin can be a promising anti-colorectal cancer agent targeting multiple cancer-promoting processes. Furthermore, this study supports expanding natural products drug discovery to freshwater niches as prospective sources of anti-cancer compounds.

The Highly Pure Neem Leaf Extract, SCNE, Inhibits Tumorigenesis in Oral Squamous Cell Carcinoma via Disruption of Pro-tumor Inflammatory Cytokines and Cell Signaling

“…SCC4, Cal27, and HSC3 cells were cultured in 96-well plates in complete growth medium. A scratch was performed using a WoundMaker and visualized using the IncuCyte ZOOM real time imaging system (Essen BioScience, MI, USA) (12, 29). Cells were treated with 20 or 60 μg/ml SCNE and 10 or 50 μM NIM and imaged at 3 h intervals for 120 h (SCC4), 72 h (Cal27), and 8 h (HSC3) to monitor cell migration and wound healing.…”

“…Cellular protein extracts were prepared and proteins quantified as described previously (12, 29–31). Briefly cells were washed twice with 1X PBS, collected by scraping and centrifuged at 4°C at 300 g for 6 min.…”

A supercritical CO2 extract of neem leaf (A. indica) and its bioactive liminoid, nimbolide, suppresses colon cancer in preclinical models by modulating pro‐inflammatory pathways

“…Mice were injected subcutaneously in the right and left flank with 3 × 10 6 HCT116 or 10 × 10 6 HT29 cells in 0.1 mL of sterile PBS as previously described . Source of AIN76A was purchased from Envigo Teklad.…”

“…Serum cytokine/chemokine profile were assessed at termination and stored at −80°C until analysis using the Bio‐Plex Pro group 1 mouse cytokine 23‐plex assay kit and analyzed with the Bio‐Plex 200 Luminex‐based multiplex analysis system (Bio‐Rad, Hercules, CA) …”

Salvianolic acid B reverses multidrug resistance in nude mice bearing human colon cancer stem cells

“…This method has been widely applied for enriching CSCs ( 8 ). A nude mouse model for colon cancer can be established via subcutaneous injection or transplantation of xenograft tumor tissues ( 9 , 10 ); however, the methods required for the establishment of a CSC mouse model require further investigation.…”