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Specific Colon Cancer Cell Cytotoxicity Induced by Bacteriophage E Gene Expression under Transcriptional Control of Carcinoembryonic Antigen Promoter.

Rama AR, Hernandez R, Perazzoli G, Burgos M, Melguizo C, Vélez C, Prados J - Int J Mol Sci (2015)

Bottom Line: The bacteriophage E gene has demonstrated significant antitumor activity in several cancers, but without any tumor-specific activity.We used the carcinoembryonic antigen promoter (CEA) to direct E gene expression (pCEA-E) towards colon cancer cells. pCEA-E induced a high cell growth inhibition of human HTC-116 colon adenocarcinoma and mouse MC-38 colon cancer cells in comparison to normal human CCD18co colon cells, which have practically undetectable levels of CEA.These results suggest that the CEA promoter is an excellent candidate for directing E gene expression specifically toward colon cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Science, University of Jaén, Jaén 23071, Spain. arama@ujaen.es.

ABSTRACT
Colorectal cancer is one of the most prevalent cancers in the world. Patients in advanced stages often develop metastases that require chemotherapy and usually show a poor response, have a low survival rate and develop considerable toxicity with adverse symptoms. Gene therapy may act as an adjuvant therapy in attempts to destroy the tumor without affecting normal host tissue. The bacteriophage E gene has demonstrated significant antitumor activity in several cancers, but without any tumor-specific activity. The use of tumor-specific promoters may help to direct the expression of therapeutic genes so they act against specific cancer cells. We used the carcinoembryonic antigen promoter (CEA) to direct E gene expression (pCEA-E) towards colon cancer cells. pCEA-E induced a high cell growth inhibition of human HTC-116 colon adenocarcinoma and mouse MC-38 colon cancer cells in comparison to normal human CCD18co colon cells, which have practically undetectable levels of CEA. In addition, in vivo analyses of mice bearing tumors induced using MC-38 cells showed a significant decrease in tumor volume after pCEA-E treatment and a low level of Ki-67 in relation to untreated tumors. These results suggest that the CEA promoter is an excellent candidate for directing E gene expression specifically toward colon cancer cells.

No MeSH data available.


Related in: MedlinePlus

Effect of pCEA-E on cell proliferation. Cells from cell lines HTC-116 (A), T-84 (B), MC-38 (C) and CCD18co (D) were transfected with pCEA-E to determine proliferation rate modulation after 24, 48 and 72 h. Data represent the mean value of three replicates ± the standard error of the mean (SEM).
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ijms-16-12601-f002: Effect of pCEA-E on cell proliferation. Cells from cell lines HTC-116 (A), T-84 (B), MC-38 (C) and CCD18co (D) were transfected with pCEA-E to determine proliferation rate modulation after 24, 48 and 72 h. Data represent the mean value of three replicates ± the standard error of the mean (SEM).

Mentions: To analyze the E gene antiproliferative effect under CEA promoter transcriptional control, we selected the colon cancer cell lines with the highest (HTC-116) and lowest (T-84) CEA promoter activity, as well as normal CCD18co cells, which presented practically CEA promoter activity. Furthermore, we analyzed MC-38 cells in order to carry out in vivo experiments. As shown in Figure 2A, HTC-116 cells transfected with the E gene showed a significant and time-dependent decrease in growth. Cell growth inhibition was 15%, 31% and 48% at 24, 48 and 72 h, respectively, after transfection and in relation to control cells. Similar results were observed for the MC-38 colon cancer cells, which were also characterized by strong CEA promoter activity (Figure 2C). By contrast, T-84 cells with weak CEA promoter activity showed proliferation inhibition levels of only 4%, 8.5% and 13.5% at 24, 48 and 72 h after transfection, respectively. CCD118co colon cells with no CEA promoter activity showed an insignificant change in the % of proliferation (see “control”).


Specific Colon Cancer Cell Cytotoxicity Induced by Bacteriophage E Gene Expression under Transcriptional Control of Carcinoembryonic Antigen Promoter.

Rama AR, Hernandez R, Perazzoli G, Burgos M, Melguizo C, Vélez C, Prados J - Int J Mol Sci (2015)

Effect of pCEA-E on cell proliferation. Cells from cell lines HTC-116 (A), T-84 (B), MC-38 (C) and CCD18co (D) were transfected with pCEA-E to determine proliferation rate modulation after 24, 48 and 72 h. Data represent the mean value of three replicates ± the standard error of the mean (SEM).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490463&req=5

ijms-16-12601-f002: Effect of pCEA-E on cell proliferation. Cells from cell lines HTC-116 (A), T-84 (B), MC-38 (C) and CCD18co (D) were transfected with pCEA-E to determine proliferation rate modulation after 24, 48 and 72 h. Data represent the mean value of three replicates ± the standard error of the mean (SEM).
Mentions: To analyze the E gene antiproliferative effect under CEA promoter transcriptional control, we selected the colon cancer cell lines with the highest (HTC-116) and lowest (T-84) CEA promoter activity, as well as normal CCD18co cells, which presented practically CEA promoter activity. Furthermore, we analyzed MC-38 cells in order to carry out in vivo experiments. As shown in Figure 2A, HTC-116 cells transfected with the E gene showed a significant and time-dependent decrease in growth. Cell growth inhibition was 15%, 31% and 48% at 24, 48 and 72 h, respectively, after transfection and in relation to control cells. Similar results were observed for the MC-38 colon cancer cells, which were also characterized by strong CEA promoter activity (Figure 2C). By contrast, T-84 cells with weak CEA promoter activity showed proliferation inhibition levels of only 4%, 8.5% and 13.5% at 24, 48 and 72 h after transfection, respectively. CCD118co colon cells with no CEA promoter activity showed an insignificant change in the % of proliferation (see “control”).

Bottom Line: The bacteriophage E gene has demonstrated significant antitumor activity in several cancers, but without any tumor-specific activity.We used the carcinoembryonic antigen promoter (CEA) to direct E gene expression (pCEA-E) towards colon cancer cells. pCEA-E induced a high cell growth inhibition of human HTC-116 colon adenocarcinoma and mouse MC-38 colon cancer cells in comparison to normal human CCD18co colon cells, which have practically undetectable levels of CEA.These results suggest that the CEA promoter is an excellent candidate for directing E gene expression specifically toward colon cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Science, University of Jaén, Jaén 23071, Spain. arama@ujaen.es.

ABSTRACT
Colorectal cancer is one of the most prevalent cancers in the world. Patients in advanced stages often develop metastases that require chemotherapy and usually show a poor response, have a low survival rate and develop considerable toxicity with adverse symptoms. Gene therapy may act as an adjuvant therapy in attempts to destroy the tumor without affecting normal host tissue. The bacteriophage E gene has demonstrated significant antitumor activity in several cancers, but without any tumor-specific activity. The use of tumor-specific promoters may help to direct the expression of therapeutic genes so they act against specific cancer cells. We used the carcinoembryonic antigen promoter (CEA) to direct E gene expression (pCEA-E) towards colon cancer cells. pCEA-E induced a high cell growth inhibition of human HTC-116 colon adenocarcinoma and mouse MC-38 colon cancer cells in comparison to normal human CCD18co colon cells, which have practically undetectable levels of CEA. In addition, in vivo analyses of mice bearing tumors induced using MC-38 cells showed a significant decrease in tumor volume after pCEA-E treatment and a low level of Ki-67 in relation to untreated tumors. These results suggest that the CEA promoter is an excellent candidate for directing E gene expression specifically toward colon cancer cells.

No MeSH data available.


Related in: MedlinePlus