[Decursin affects proliferation, apoptosis, and migration of colorectal cancer cells through PI3K/Akt signaling pathway]

by Selleckchem | Sep 15 2023

We investigated the effects of decursin on the proliferation, apoptosis, and migration of colorectal cancer HT29 and HCT116 cells through the phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway. Decursin(10, 30, 60, and 90 μmol·L~(-1)) was used to treat HT29 and HCT116 cells. The survival, colony formation ability, proliferation, apoptosis, wound hea-ling area, and migration of the HT29 and HCT116 cells exposed to decursin were examined by cell counting kit-8(CCK8), cloning formation experiments, Ki67 immunofluorescence staining, flow cytometry, wound healing assay, and Transwell assay, respectively. Western blot was employed to determine the expression levels of epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), vimentin, B-cell lymphoma/leukemia-2(Bcl-2), Bcl-2-associated X protein(Bax), tumor suppressor protein p53, PI3K, and Akt. Compared with the control group, decursin significantly inhibited the proliferation and colony number and promoted the apoptosis of HT29 and HCT116 cells, and it significantly down-regulated the expression of Bcl-2 and up-regulated the expression of Bax. Decursin inhibited the wound healing and migration of the cells, significantly down-regulated the expression of N-cadherin and vimentin, and up-regulated the expression of E-cadherin. In addition, it significantly down-regulated the expression of PI3K and Akt and up-regulated that of p53. In summary, decursin may regulate epithelial-mesenchymal transition(EMT) via the PI3K/Akt signaling pathway, thereby affecting the proliferation, apoptosis, and migration of colorectal cancer cells.

Comments:

The study you described investigated the effects of decursin, a natural compound, on colorectal cancer cells (HT29 and HCT116) and explored its potential mechanisms of action. Here's a summary of the findings:

1. Treatment with different concentrations of decursin (10, 30, 60, and 90 μmol·L^(-1)) significantly inhibited the proliferation and colony formation ability of HT29 and HCT116 cells. This suggests that decursin has anti-proliferative effects on colorectal cancer cells.

2. Decursin treatment promoted apoptosis in both HT29 and HCT116 cells. Apoptosis is a programmed cell death process that helps eliminate damaged or abnormal cells. By enhancing apoptosis, decursin may contribute to the suppression of colorectal cancer cell growth.

3. Decursin inhibited wound healing and migration of HT29 and HCT116 cells. This indicates that decursin can impede the ability of these cancer cells to migrate and invade surrounding tissues.

4. The expression levels of various proteins were measured to understand the underlying mechanisms of decursin's effects. Decursin treatment resulted in the downregulation of Bcl-2, an anti-apoptotic protein, and the upregulation of Bax, a pro-apoptotic protein. This shift in the balance between pro- and anti-apoptotic proteins likely contributes to decursin-induced apoptosis.

5. Decursin treatment also led to the downregulation of N-cadherin and vimentin, which are proteins associated with mesenchymal cell characteristics, and the upregulation of E-cadherin, which is associated with epithelial cell characteristics. These changes indicate that decursin may regulate a process called epithelial-mesenchymal transition (EMT). EMT is a biological process involved in cancer progression, where cells acquire mesenchymal properties, including increased migratory and invasive capabilities.

6. The PI3K/Akt signaling pathway was investigated in this study. Decursin treatment resulted in the downregulation of PI3K and Akt, which are key components of this pathway. The PI3K/Akt pathway is known to play a crucial role in cell survival, proliferation, and migration. By inhibiting this pathway, decursin may contribute to the suppression of colorectal cancer cell growth and migration.

7. Decursin treatment upregulated the expression of tumor suppressor protein p53. p53 is a well-known tumor suppressor that regulates cell cycle arrest, DNA repair, and apoptosis. The upregulation of p53 by decursin suggests its involvement in the anti-cancer effects of decursin.

In summary, the findings suggest that decursin has inhibitory effects on colorectal cancer cells. It can suppress proliferation, promote apoptosis, inhibit migration, and regulate EMT through modulation of the PI3K/Akt signaling pathway. These results highlight the potential of decursin as a therapeutic agent for colorectal cancer, although further studies are needed to validate its efficacy and safety in preclinical and clinical settings.