Combination of CYP inhibitor with MEK/ERK inhibitor enhances the inhibitory effect on erk in braf mutant colon cancer cells

Sun Min Lim, Jee Won Hwang, Joong Bae Ahn, Soo Kyung Bae, Chan Hee Park, Ki Yeol Kim, SunYoung Rha, Hyuncheol Chung, Jae Kyung Roh, Sang Joon Shin

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background/Aim: To investigate mechanisms of discrepancy in response to a MEK/ERK inhibitor, U0126, in KRAS- and BRAF-mutant colorectal cancer cells. Materials and Methods: Multiparametric flow cytometry was performed on two colon cancer cell lines, HCT116 and HT29. Cells were treated with U0126, and phospho-specific antibodies were used to monitor ERK signaling. Results: HCT116 and HT29 cells were treated with increasing amounts of U0126. The western blot analysis revealed that by increasing the amount of U0126 resulted in inhibition of phospho-ERK, in HCT116 and to a lesser degree in HT29 cells. Microarray profiling identified CYP1A1 and 1A2 overexpression in HT29 cells and that inhibition of CYP1A1 with a-naphthoflavone and furanfylline restored sensitivity to U0126 in HT29 cells. Conclusion: Combination of a CYP inhibitor with MEK/ERK inhibitor enhances the inhibitory effect on ERK in BRAF-mutant colon cancer cells.

Original languageEnglish
Pages (from-to)2499-2508
Number of pages10
JournalAnticancer Research
Volume33
Issue number6
Publication statusPublished - 2013 Jun 1

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Mitogen-Activated Protein Kinase Kinases
HT29 Cells
Colonic Neoplasms
Cytochrome P-450 CYP1A1
Phospho-Specific Antibodies
HCT116 Cells
Colorectal Neoplasms
Flow Cytometry
Western Blotting
U 0126
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Lim, S. M., Hwang, J. W., Ahn, J. B., Bae, S. K., Park, C. H., Kim, K. Y., ... Shin, S. J. (2013). Combination of CYP inhibitor with MEK/ERK inhibitor enhances the inhibitory effect on erk in braf mutant colon cancer cells. Anticancer Research, 33(6), 2499-2508.
Lim, Sun Min ; Hwang, Jee Won ; Ahn, Joong Bae ; Bae, Soo Kyung ; Park, Chan Hee ; Kim, Ki Yeol ; Rha, SunYoung ; Chung, Hyuncheol ; Roh, Jae Kyung ; Shin, Sang Joon. / Combination of CYP inhibitor with MEK/ERK inhibitor enhances the inhibitory effect on erk in braf mutant colon cancer cells. In: Anticancer Research. 2013 ; Vol. 33, No. 6. pp. 2499-2508.
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abstract = "Background/Aim: To investigate mechanisms of discrepancy in response to a MEK/ERK inhibitor, U0126, in KRAS- and BRAF-mutant colorectal cancer cells. Materials and Methods: Multiparametric flow cytometry was performed on two colon cancer cell lines, HCT116 and HT29. Cells were treated with U0126, and phospho-specific antibodies were used to monitor ERK signaling. Results: HCT116 and HT29 cells were treated with increasing amounts of U0126. The western blot analysis revealed that by increasing the amount of U0126 resulted in inhibition of phospho-ERK, in HCT116 and to a lesser degree in HT29 cells. Microarray profiling identified CYP1A1 and 1A2 overexpression in HT29 cells and that inhibition of CYP1A1 with a-naphthoflavone and furanfylline restored sensitivity to U0126 in HT29 cells. Conclusion: Combination of a CYP inhibitor with MEK/ERK inhibitor enhances the inhibitory effect on ERK in BRAF-mutant colon cancer cells.",
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Lim, SM, Hwang, JW, Ahn, JB, Bae, SK, Park, CH, Kim, KY, Rha, S, Chung, H, Roh, JK & Shin, SJ 2013, 'Combination of CYP inhibitor with MEK/ERK inhibitor enhances the inhibitory effect on erk in braf mutant colon cancer cells', Anticancer Research, vol. 33, no. 6, pp. 2499-2508.

Combination of CYP inhibitor with MEK/ERK inhibitor enhances the inhibitory effect on erk in braf mutant colon cancer cells. / Lim, Sun Min; Hwang, Jee Won; Ahn, Joong Bae; Bae, Soo Kyung; Park, Chan Hee; Kim, Ki Yeol; Rha, SunYoung; Chung, Hyuncheol; Roh, Jae Kyung; Shin, Sang Joon.

In: Anticancer Research, Vol. 33, No. 6, 01.06.2013, p. 2499-2508.

Research output: Contribution to journalArticle

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T1 - Combination of CYP inhibitor with MEK/ERK inhibitor enhances the inhibitory effect on erk in braf mutant colon cancer cells

AU - Lim, Sun Min

AU - Hwang, Jee Won

AU - Ahn, Joong Bae

AU - Bae, Soo Kyung

AU - Park, Chan Hee

AU - Kim, Ki Yeol

AU - Rha, SunYoung

AU - Chung, Hyuncheol

AU - Roh, Jae Kyung

AU - Shin, Sang Joon

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Background/Aim: To investigate mechanisms of discrepancy in response to a MEK/ERK inhibitor, U0126, in KRAS- and BRAF-mutant colorectal cancer cells. Materials and Methods: Multiparametric flow cytometry was performed on two colon cancer cell lines, HCT116 and HT29. Cells were treated with U0126, and phospho-specific antibodies were used to monitor ERK signaling. Results: HCT116 and HT29 cells were treated with increasing amounts of U0126. The western blot analysis revealed that by increasing the amount of U0126 resulted in inhibition of phospho-ERK, in HCT116 and to a lesser degree in HT29 cells. Microarray profiling identified CYP1A1 and 1A2 overexpression in HT29 cells and that inhibition of CYP1A1 with a-naphthoflavone and furanfylline restored sensitivity to U0126 in HT29 cells. Conclusion: Combination of a CYP inhibitor with MEK/ERK inhibitor enhances the inhibitory effect on ERK in BRAF-mutant colon cancer cells.

AB - Background/Aim: To investigate mechanisms of discrepancy in response to a MEK/ERK inhibitor, U0126, in KRAS- and BRAF-mutant colorectal cancer cells. Materials and Methods: Multiparametric flow cytometry was performed on two colon cancer cell lines, HCT116 and HT29. Cells were treated with U0126, and phospho-specific antibodies were used to monitor ERK signaling. Results: HCT116 and HT29 cells were treated with increasing amounts of U0126. The western blot analysis revealed that by increasing the amount of U0126 resulted in inhibition of phospho-ERK, in HCT116 and to a lesser degree in HT29 cells. Microarray profiling identified CYP1A1 and 1A2 overexpression in HT29 cells and that inhibition of CYP1A1 with a-naphthoflavone and furanfylline restored sensitivity to U0126 in HT29 cells. Conclusion: Combination of a CYP inhibitor with MEK/ERK inhibitor enhances the inhibitory effect on ERK in BRAF-mutant colon cancer cells.

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