Anticancer Effects of Colchicine on Hypopharyngeal Cancer

Abstract

Colchicine is an alkaloid widely used for the treatment of inflammatory diseases, such as gout. It suppresses cell division by inhibiting mitosis. We investigated the anticancer effects of colchicine on human hypopharyngeal cancer cells and the mechanisms underlying its anticancer effects. XTT cell proliferation assay showed that colchicine inhibited the growth and proliferation of human hypopharyngeal cancer cells (FaDu and SNU1041) in a dose- and time-dependent manner. Colchicine also inhibited the migration, invasion, and adhesion of hypopharyngeal cancer cells in a dose-dependent manner. The levels of mRNA expression and activity of matrix metalloproteinase-9 (MMP9) and urokinase-type plasminogen activator (uPA) decreased after treatment with colchicine. Further investigation revealed that colchicine inhibited the phosphorylation of the FAK/SRC complex and paxillin. Tumor volume ratios in colchicine-treated mice (0.1 mg/kg, every 2 days for 14 days) increased less than in control mice. To our knowledge, this is the first report showing that colchicine can suppress cell invasion, migration, and adhesion through reduced expression of MMP9, the uPA system, and the FAK/SRC complex. Colchicine has the potential to prevent disease progression in hypopharyngeal cancer and may have application as an adjunctive treatment.

Animal models of chemotherapy-induced cognitive decline in preclinical drug development

“…Colchicine exhibited the anti-cancer effects in prostate adenocarcinoma cell line MAT-LyLu (MLL) and human prostate cancer cells (PC-3) and also in male Copenhagen rats treated intraperitoneally (given as 0.1% from 10 mg/ml of stock solution) for 9 days (Fakih et al 1995). Reactive oxygen species-mediated cell death and anti-tumor effects of colchicine were also reported in human hypopharyngeal cancer cell lines (Cho et al 2017), lung cancer cell lines (Bhattacharya et al 2016), pancreatic cancer cell lines (Larocque et al 2014), and breast cancer cell lines (Sun et al 2016). But the pharmaceutical importance of colchicine for its anticancer activity is questionable because of its very narrow (Nokia et al 2012) therapeutic index, so the monitoring of drug plasma concentration is Despite its anti-cancer effects, colchicine is a neurotoxic agent that induces neurofibrillary degeneration, depletion of antioxidant defense system, and loss of cholinergic neurons with marked destruction of hippocampal granule cells and septohippocampal pathway affecting learning and memory (Table 10).…”

Plants in Anticancer Drug Discovery: From Molecular Mechanism to Chemoprevention

“…Colchicine blocks the cell cycle at the G2/M phase inhibiting the action of tubulin, thereby the formation of microtubule severely damages the internal scaffolding of the cells and trigger apoptosis [ 120 ]. Owing to its high toxicity, colchicine has not found significant use in cancer treatment; however, it is still used as a lead compound for the generation of potential anticancer drugs [ 121 ].…”

Targeted Nano-Drug Delivery of Colchicine against Colon Cancer Cells by Means of Mesoporous Silica Nanoparticles

“…Despite COL not yet being used clinically for cancer therapy because of its toxicity to normal cells, it is used as a lead compound in generating potent anticancer agents [5][6][7][8][9]. To reduce the side effects of COL on normal cells, many types of research have included analogs of COL [10,11] and combination treatments with other drugs [12].…”