5-Fluorouracil induces apoptosis in human colon cancer cell lines with modulation of Bcl-2 family proteins

Abstract

Summary Recently. apoptosis has been implicated as one of the end points of cells exposed to chemotherapeutic agents. The p53 and Bcl-2 family of proteins are involved in chemotherapy-induced apoptosis. but in a cell type-dependent manner. We sought to determine the roles played by the p53 and Bcl-2 family of proteins in 5-fluorouracil (5-FU)-induced apoptosis of human colon cancer cell lines. We first studied the p53 genetic and functional status, and then 5-FU, at inhibitory concentration of 50% (ICj)

Resistance of colon cancer cells to long‐term 5‐fluorouracil exposure is correlated to the relative level of Bcl‐2 and Bcl‐XL in addition to Bax and p53 status

“…Unlike our results (Table I), HT-29 and LoVo cells were considered after short exposure as 5-FU resistant and sensitive cells, respectively. 3,22 By analysis of cell growth, we show that 5-FU does not affect the growth of HT-29 before the 4th or 5th day of culture which contrast with LoVo (Fig. 3).…”

“…3,4 Thus, alterations in genes related to this process can have profound impacts on chemotherapy and can participate to development of 5-FU resistance by tumoral cells. Among genes of the apoptotic pathway, the p53 tumor suppressor gene is involved in G1 growth arrest by inducing the cyclin dependent kinase inhibitor p21/WAF1 and also in apoptosis through transactivation of the pro-apoptotic bax gene in response to DNA-damage.…”

“…16,20 Recently, it has been suggested that the ratio of Bcl-x L to Bax may be related to chemosensitivity to 5-FU. 3 Very few data, in vivo or in vitro, have been reported to firmly establish a relationship between the genotype and/or phenotype of p53, Bax, Bcl-2 and Bcl-x L proteins and the level of response to 5-FU treatment of tumoral cells. A major difficulty encountered in vivo is to compare the expression of apoptotic genes in tumors before and after treatment.…”

“…A major difficulty encountered in vivo is to compare the expression of apoptotic genes in tumors before and after treatment. In vitro, the majority of the observations of cell death have been made after short times (24 -72 hr) of exposure to high 5-FU doses, 3,21,22 and thus differ from the conditions used in long-term therapy in vivo. 23 The aim of our study was to evaluate the accuracy of apoptosis-related proteins as markers allowing a better prediction of 5-FU resistance of tumoral cells.…”

Overexpression of hRFI inhibits 5-fluorouracil-induced apoptosis in colorectal cancer cells via activation of NF-κB and upregulation of BCL-2 and BCL-XL

“…Finally, the apoptosis regulators are known to be closely related to both chemosensitivity and prognosis in colorectal cancer (Kahlenberg et al, 2003). In particular, the expression of Bcl-2 family proteins is an important determinant of the chemosensitivity to 5-FU in colorectal cancer cells (Maurer et al, 1998;Ogura et al, 1999;Nita et al, 1998Nita et al, , 2000Violette et al, 2002). We have revealed in this study that hRFI overexpression in colorectal cancer cells elicits an increase of IC 50 values towards 5-FU as well as the specific upregulation of Bcl-2 and Bcl-XL.…”