Ceramide involvement in homocamptothecin- and camptothecin-induced cytotoxicity and apoptosis in colon HT29 cells

  • Authors:
    • D. Chauvier
    • H. Morjani
    • M. Manfait
  • View Affiliations

  • Published online on: April 1, 2002     https://doi.org/10.3892/ijo.20.4.855
  • Pages: 855-863
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Topoisomerase I inhibitors of the camptothecin (CPT) family have emerged as potent clinical chemotherapeutic agents in first-line treatment of solid colorectal cancer and in second-line for 5-fluorouracil resistant patients. CPT and homocamptothecin (hCPT), derivative with enhanced lactone stability, induced growth inhibition in HT29 cells via p53-independent apoptosis. hCPT- and CPT-induced apoptosis was dependent on caspase-3 but not caspase-1. We report here substantial evidence that ceramide, resulting from de novo pathway or catabolism modulation, acted as a second messenger of these antitumor drugs in HT29 cells and leads to the activation of caspase-3. In addition, hCPT and CPT may favor ceramide signaling by disturbing sites of synthesis (Golgi) and trafficking of glucosylceramide from Golgi to lipid droplets. This work contributes to the understanding of the mechanism of action of CPTs, and suggests that inhibitors of glycosylation or activators of de novo metabolism could be of clinical interest in enhancing the effects of CPTs.

Related Articles

Journal Cover

April 2002
Volume 20 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Chauvier D, Morjani H and Manfait M: Ceramide involvement in homocamptothecin- and camptothecin-induced cytotoxicity and apoptosis in colon HT29 cells. Int J Oncol 20: 855-863, 2002
APA
Chauvier, D., Morjani, H., & Manfait, M. (2002). Ceramide involvement in homocamptothecin- and camptothecin-induced cytotoxicity and apoptosis in colon HT29 cells. International Journal of Oncology, 20, 855-863. https://doi.org/10.3892/ijo.20.4.855
MLA
Chauvier, D., Morjani, H., Manfait, M."Ceramide involvement in homocamptothecin- and camptothecin-induced cytotoxicity and apoptosis in colon HT29 cells". International Journal of Oncology 20.4 (2002): 855-863.
Chicago
Chauvier, D., Morjani, H., Manfait, M."Ceramide involvement in homocamptothecin- and camptothecin-induced cytotoxicity and apoptosis in colon HT29 cells". International Journal of Oncology 20, no. 4 (2002): 855-863. https://doi.org/10.3892/ijo.20.4.855