Colchicine induces apoptosis in HT-29 human colon cancer cells via the AKT and c-Jun N-terminal kinase signaling pathways

Abstract

Colchicine is a natural compound, which belongs to the botanical family Colchicaceae and prevents growth of cancer cells via antimitotic activity by interacting with microtubules. Although numerous studies have demonstrated that the effect of colchicine on cell apoptosis is mediated by the activation of caspase‑3, the signaling pathways involved in the process remain unknown. In the current study, evidence is presented regarding the missing information using HT‑29 human colon cancer cells. The effect of colchicine on apoptosis in HT‑29 cells and the apoptosis‑associated signaling pathways were determined using various methods, including cell viability assay, Annexin V/propidium idodide (PI) binding, PI staining, Hoechst 33342 staining, mitochondrial membrane potential (Δψm) assay, reactive oxygen species (ROS) assay and western blot analysis. Colchicine was observed to induce a dose‑dependent reduction in cell viability in HT‑29 cells and early apoptosis occurred when the cells were treated with 1 µg/ml colchicine. Furthermore, colchicine treatment induced a loss of Δψm, increased ROS production, activated caspase‑3, upregulated BAX expression and downregulated Bcl‑2 expression, which evidenced the colchicine activity on apoptosis, potentially by acting via the intrinsic apoptotic signaling pathway. Colchicine increased phosphorylation of p38, although not phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase, which indicates that colchicine activates the p38 signaling pathway in order to induce cell apoptosis. Therefore, colchicine exhibited significant growth inhibition of the HT‑29 colon cancer cell line and induced apoptosis in the cells via the mitochondrial pathway, which is regulated by p38 signaling pathways.

Activation of PERK Contributes to Apoptosis and G2/M Arrest by Microtubule Disruptors in Human Colorectal Carcinoma Cells

“…The differential roles of JNK activation in MTA-induced anticancer effects were previously reported. Huang et al [47] reported that colchicine induced apoptosis of HT-29 cells via JNK activation. Wang et al [48] indicated that JNK activation was involved in TAX-induced apoptosis.…”

Effects of Colchicine on Cell Cycle Arrest and MMP-2 mRNA Expression in MCF 7 Breast Adenocarcinoma Cells

“…Colchicine causes antiproliferative effects through the inhibition of microtubule formation, which leads to mitotic arrest and cell death by apoptosis (13). Previous studies also reported that colchicine and its potent derivatives showed a favorable therapeutic effect on hypopharyngeal, pancreatic, gastric, colon and hepatocellular carcinoma (10,(13)(14)(15)(16)(17). In conclusion, the results of our study indicate that colchicine can be identified as a potential anticancer compound for MCF-7 breast cancer cell line.…”

5-(Furan-2-yl)-4-(3,4,5-trimethoxyphenyl)-3H-1,2-dithiol-3- one oxime (6f), a new synthetic compound, causes human fibrosarcoma HT-1080 cell apoptosis by disrupting tubulin polymerisation and inducing G2/M arrest

“…Several microtubule-targeted agents, including vinca alkaloids, taxanes and colchicine, bind to tubulin and alter the polymerisation dynamics of microtubules, in turn disrupting cell cycle and inducing apoptosis (23)(24)(25). Therefore, in the present study, the effect of 6f on cell cycle progression was tested by flow cytometry.…”