Article Sidebar
Published:
Aug 2, 2017Keywords:
Article Details
Submission of a manuscript to this journal is a representation that the manuscript has not been published previously and is not under consideration for publication elsewhere.
All authors named in each manuscript would be required to sign a form (to be supplied by the Editor) so that they may retain their copyright in the article but to assign to us (the Publishers) and its licensees in perpetuity, in all forms, formats and media (whether known or created in the future) to (i) publish, reproduce, distribute, display and store the contribution, (ii) translate the contribution into other languages, create adaptations, reprints, include within collections and create summaries, extracts and/or abstracts of the contribution, (iii) create any other derivative works(s) based on the contribution, (iv) to exploit all subsidiary rights in the contribution, (v) the inclusion of electronic links from the contribution to third party material where-ever it may be located, and (vi) license any thrid party to do any or all of the above.
Main Article Content
Capecitabine treatment of HCT-15 colon cancer cells induces apoptosis via mitochondrial pathway
Abstract
Purpose: To investigate the effect of capecitabine on apoptosis induction in HCT-15 colon carcinoma cells and investigate the underlying mechanism.
Methods: Phase-contrast microscopy was used for the examination of morphological changes while flow cytometry was employed for the analysis of cell cycle distribution, induction of apoptosis, reactive oxygen species (ROS) production and expression of caspases. Western blot assay was used for the analysis of expression level of apoptosis-related and cell cycle regulatory proteins.
Results: Capecitabine treatment caused changes in the morphological appearance of HCT-15 cells after 48 h. The viability of HCT-15 cells was reduced to 23 % on treatment with capecitabine (5 μM) compared to 98 % in the control cultures. Incubation with capecitabine increased the population of HCT- 15 cells in G0/G1 phase to 56.43 % compared to 41.67 % in the control. Capecitabine treatment of HCT-15 cells caused condensation of DNA and induced apoptosis in a concentration-dependent manner. At 5 μM concentration of capecitabine, apoptosis was induced in 45.74 % of the cells. Incubation of HCT-15 cells with capecitabine for 48 h led to a significant increase in the production of ROS. Translocation of Endo G and AIF from mitochondria to the nuclei increased significantly (p < 0.005) on treatment with 5 μM capecitabine. Capecitabine treatment also reduced the expression of cyclin E and Cdc25c and promoted the level of caspases, Bax, AIF, Endo G, p21, PARP and p-p53. The expression level of Bcl-2 decreased in HCT-15 cells on incubation with 5 μM concentration of capecitabine.
Conclusion: Capecitabine treatment causes inhibition of colon cancer growth via the mitochondrial pathway of apoptosis. Thus, capecitabine may have therapeutic application in colon carcinoma treatment.
Keywords: Capecitabine, 5-Fluorouracil, Translocation, Colon cancer, Colitis, Apoptosis
