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Overexpression of CYP3A4 in a COLO 205 Colon Cancer Stem Cell Model in vitro.

Olszewski U, Liedauer R, Ausch C, Thalhammer T, Hamilton G - Cancers (Basel) (2011)

Bottom Line: We established an in vitro colon CSC-like model using the COLO 205 cell line, which revealed transiently increased expression of CD133 when transferred to serum-free stem cell culture medium.Assessment of global gene expression of COLO 205 cells under these conditions identified a set of upregulated genes including cytochrome P450 3A4 (CYP3A4) and aldehyde dehydrogenase 1A1 (ALDH1A1), as confirmed by real-time qPCR.In conclusion, this COLO 205 model provides evidence for CD133 induction concomitant with overexpression of CYP3A4, which, together with ATP-binding cassette, subfamily G, member 2 (ABCG2) and others, may have a role in chemoresistant colon CSCs and a negative impact on disease-free survival in colon cancer patients.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Boltzmann Cluster of Translational Oncology, c/o Balderichgasse 26/13, A-1170 Vienna, Austria. gerhard.hamilton@toc.lbg.ac.at.

ABSTRACT
Cancer stem cells (CSCs) seem to constitute a subpopulation of tumor cells that escape from chemotherapy and cause recurrent disease. Low proliferation rates, protection in a stem cell niche and overexpression of drug resistance proteins are considered to confer chemoresistance. We established an in vitro colon CSC-like model using the COLO 205 cell line, which revealed transiently increased expression of CD133 when transferred to serum-free stem cell culture medium. Assessment of global gene expression of COLO 205 cells under these conditions identified a set of upregulated genes including cytochrome P450 3A4 (CYP3A4) and aldehyde dehydrogenase 1A1 (ALDH1A1), as confirmed by real-time qPCR. ALDH1A1 is a CSC marker for certain tumor entities and confers resistance to cyclophosphamide. CYP3A4 is expressed in liver and colon and its overexpression seems particularly relevant in colon cancer, since it inactivates irinotecan and other xenobiotics, such as taxols and vinca alkaloids. In conclusion, this COLO 205 model provides evidence for CD133 induction concomitant with overexpression of CYP3A4, which, together with ATP-binding cassette, subfamily G, member 2 (ABCG2) and others, may have a role in chemoresistant colon CSCs and a negative impact on disease-free survival in colon cancer patients.

No MeSH data available.


Related in: MedlinePlus

Comparison of chemosensitivities of COLO 205 cells precultivated in either standard medium or serum-free stem cell medium. Viability of COLO 205 colon cancer cells precultivated in either normal tissue culture (con) or stem cell medium (CSC-like) after exposure to a range of chemotherapeutics in normal tissue culture medium for four days in vitro (mean ± SD). All differences were statistically significant, except for satraplatin.
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f2-cancers-03-01467: Comparison of chemosensitivities of COLO 205 cells precultivated in either standard medium or serum-free stem cell medium. Viability of COLO 205 colon cancer cells precultivated in either normal tissue culture (con) or stem cell medium (CSC-like) after exposure to a range of chemotherapeutics in normal tissue culture medium for four days in vitro (mean ± SD). All differences were statistically significant, except for satraplatin.

Mentions: Chemosensitivity of COLO 205 cells cultivated in either standard tissue culture or serum-free stem cell medium in vitro was evaluated in MTT assays (Figure 2). Survival of cells was compared for a range of drugs used in definite concentrations near their respective IC50 values, with exception of cisplatin and titanocene Y. The IC50 values for COLO 205 cells had been calculated from dose-response-curves obtained in MTT assays using 6–8 two-fold dilution steps of the compounds in previous experiments (data not shown). Thus, drug concentrations deduced from these tests were 5 μg/mL for oxoplatin, 0.5 μg/mL for cisplatin, 1 μg/mL for gemcitabine, 2.5 μg/mL for doxorubicin, 1 μg/mL for vinblastine, 0.25 μg/mL for etoposide, 2.5 μg/mL (5 μM) for satraplatin and 25 μg/mL for titanocene Y, respectively. COLO 205 cells precultivated in serum-free stem cell medium revealed a significant increase in resistance to most cytotoxic drugs, except for satraplatin with comparable sensitivity for standard and stem cell-like cells and titanocene Y, which showed higher activity against the latter cells.


Overexpression of CYP3A4 in a COLO 205 Colon Cancer Stem Cell Model in vitro.

Olszewski U, Liedauer R, Ausch C, Thalhammer T, Hamilton G - Cancers (Basel) (2011)

Comparison of chemosensitivities of COLO 205 cells precultivated in either standard medium or serum-free stem cell medium. Viability of COLO 205 colon cancer cells precultivated in either normal tissue culture (con) or stem cell medium (CSC-like) after exposure to a range of chemotherapeutics in normal tissue culture medium for four days in vitro (mean ± SD). All differences were statistically significant, except for satraplatin.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3756423&req=5

f2-cancers-03-01467: Comparison of chemosensitivities of COLO 205 cells precultivated in either standard medium or serum-free stem cell medium. Viability of COLO 205 colon cancer cells precultivated in either normal tissue culture (con) or stem cell medium (CSC-like) after exposure to a range of chemotherapeutics in normal tissue culture medium for four days in vitro (mean ± SD). All differences were statistically significant, except for satraplatin.
Mentions: Chemosensitivity of COLO 205 cells cultivated in either standard tissue culture or serum-free stem cell medium in vitro was evaluated in MTT assays (Figure 2). Survival of cells was compared for a range of drugs used in definite concentrations near their respective IC50 values, with exception of cisplatin and titanocene Y. The IC50 values for COLO 205 cells had been calculated from dose-response-curves obtained in MTT assays using 6–8 two-fold dilution steps of the compounds in previous experiments (data not shown). Thus, drug concentrations deduced from these tests were 5 μg/mL for oxoplatin, 0.5 μg/mL for cisplatin, 1 μg/mL for gemcitabine, 2.5 μg/mL for doxorubicin, 1 μg/mL for vinblastine, 0.25 μg/mL for etoposide, 2.5 μg/mL (5 μM) for satraplatin and 25 μg/mL for titanocene Y, respectively. COLO 205 cells precultivated in serum-free stem cell medium revealed a significant increase in resistance to most cytotoxic drugs, except for satraplatin with comparable sensitivity for standard and stem cell-like cells and titanocene Y, which showed higher activity against the latter cells.

Bottom Line: We established an in vitro colon CSC-like model using the COLO 205 cell line, which revealed transiently increased expression of CD133 when transferred to serum-free stem cell culture medium.Assessment of global gene expression of COLO 205 cells under these conditions identified a set of upregulated genes including cytochrome P450 3A4 (CYP3A4) and aldehyde dehydrogenase 1A1 (ALDH1A1), as confirmed by real-time qPCR.In conclusion, this COLO 205 model provides evidence for CD133 induction concomitant with overexpression of CYP3A4, which, together with ATP-binding cassette, subfamily G, member 2 (ABCG2) and others, may have a role in chemoresistant colon CSCs and a negative impact on disease-free survival in colon cancer patients.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Boltzmann Cluster of Translational Oncology, c/o Balderichgasse 26/13, A-1170 Vienna, Austria. gerhard.hamilton@toc.lbg.ac.at.

ABSTRACT
Cancer stem cells (CSCs) seem to constitute a subpopulation of tumor cells that escape from chemotherapy and cause recurrent disease. Low proliferation rates, protection in a stem cell niche and overexpression of drug resistance proteins are considered to confer chemoresistance. We established an in vitro colon CSC-like model using the COLO 205 cell line, which revealed transiently increased expression of CD133 when transferred to serum-free stem cell culture medium. Assessment of global gene expression of COLO 205 cells under these conditions identified a set of upregulated genes including cytochrome P450 3A4 (CYP3A4) and aldehyde dehydrogenase 1A1 (ALDH1A1), as confirmed by real-time qPCR. ALDH1A1 is a CSC marker for certain tumor entities and confers resistance to cyclophosphamide. CYP3A4 is expressed in liver and colon and its overexpression seems particularly relevant in colon cancer, since it inactivates irinotecan and other xenobiotics, such as taxols and vinca alkaloids. In conclusion, this COLO 205 model provides evidence for CD133 induction concomitant with overexpression of CYP3A4, which, together with ATP-binding cassette, subfamily G, member 2 (ABCG2) and others, may have a role in chemoresistant colon CSCs and a negative impact on disease-free survival in colon cancer patients.

No MeSH data available.


Related in: MedlinePlus