2,3-Diaryl-2H-1-benzopyran derivatives interfere with classical and non-classical estrogen receptor signaling pathways, inhibit Akt activation and induce apoptosis in human endometrial cancer cells

Iram Fatima, V. Chandra, R. Saxena, M. Manohar, Y. Sanghani, K. Hajela, M. P.S. Negi, P. L. Sankhwar, S. K. Jain, A. Dwivedi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Objectives: The present study was undertaken to explore the mechanism of anti-proliferative action of benzopyran compound D1 (2-[piperidinoethoxyphenyl]-3-phenyl-2H-benzopyran) and its hydroxy-(D2) and methoxy-(D3) derivatives in Ishikawa and human primary endometrial adenocarcinoma cells. Methods: Transcriptional activation assays were performed using luciferase reporter system and cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The stage of cell cycle was determined by flow-cytometry and real time analysis of cyclinE1 and cdc2 genes. The apoptotic effects were measured by AnnexinV/PI staining and TUNEL. The expression of PCNA, cyclinD1, pAkt, XIAP, cleaved caspase-9, -3, PARP, Bax and Bcl2 were determined by immunoblotting. The caspase-3 activity and mitochondrial membrane potential were measured by colorimetric assay. Results: All three compounds inhibited E 2 -induced ERE- and AP-1-mediated transactivation and proliferation in endometrial adenocarcinoma cells dose-dependently. Compound D1 caused the arrest of cells in the G 2 phase while D2 and D3 caused arrest in G 1 phase of the cell cycle. All compounds interfered with Akt activation, decreased XIAP expression leading to an increased cleavage of caspase-9, -3, PARP, increased Bax/Bcl2 ratio and caspase-3 activity. Conclusion: Findings suggest that benzopyran derivatives inhibit cellular proliferation via modulating ER-dependent classical and non-classical signaling mechanisms, interfere with Akt activation and induce apoptosis via intrinsic pathway in endometrial adenocarcinoma cells.

Original languageEnglish (US)
Pages (from-to)198-210
Number of pages13
JournalMolecular and Cellular Endocrinology
Volume348
Issue number1
DOIs
StatePublished - Jan 2 2012

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Benzopyrans
Endometrial Neoplasms
Caspase 3
Estrogen Receptors
Caspase 9
Chemical activation
Cells
Apoptosis
Derivatives
Adenocarcinoma
Assays
Transcriptional Activation
Cell Cycle
Flow cytometry
Transcription Factor AP-1
Proliferating Cell Nuclear Antigen
Luciferases
Gastrin-Secreting Cells
Mitochondrial Membrane Potential
In Situ Nick-End Labeling

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

2,3-Diaryl-2H-1-benzopyran derivatives interfere with classical and non-classical estrogen receptor signaling pathways, inhibit Akt activation and induce apoptosis in human endometrial cancer cells. / Fatima, Iram; Chandra, V.; Saxena, R.; Manohar, M.; Sanghani, Y.; Hajela, K.; Negi, M. P.S.; Sankhwar, P. L.; Jain, S. K.; Dwivedi, A.

In: Molecular and Cellular Endocrinology, Vol. 348, No. 1, 02.01.2012, p. 198-210.

Research output: Contribution to journalArticle

Fatima, Iram ; Chandra, V. ; Saxena, R. ; Manohar, M. ; Sanghani, Y. ; Hajela, K. ; Negi, M. P.S. ; Sankhwar, P. L. ; Jain, S. K. ; Dwivedi, A. / 2,3-Diaryl-2H-1-benzopyran derivatives interfere with classical and non-classical estrogen receptor signaling pathways, inhibit Akt activation and induce apoptosis in human endometrial cancer cells. In: Molecular and Cellular Endocrinology. 2012 ; Vol. 348, No. 1. pp. 198-210.
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abstract = "Objectives: The present study was undertaken to explore the mechanism of anti-proliferative action of benzopyran compound D1 (2-[piperidinoethoxyphenyl]-3-phenyl-2H-benzopyran) and its hydroxy-(D2) and methoxy-(D3) derivatives in Ishikawa and human primary endometrial adenocarcinoma cells. Methods: Transcriptional activation assays were performed using luciferase reporter system and cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The stage of cell cycle was determined by flow-cytometry and real time analysis of cyclinE1 and cdc2 genes. The apoptotic effects were measured by AnnexinV/PI staining and TUNEL. The expression of PCNA, cyclinD1, pAkt, XIAP, cleaved caspase-9, -3, PARP, Bax and Bcl2 were determined by immunoblotting. The caspase-3 activity and mitochondrial membrane potential were measured by colorimetric assay. Results: All three compounds inhibited E 2 -induced ERE- and AP-1-mediated transactivation and proliferation in endometrial adenocarcinoma cells dose-dependently. Compound D1 caused the arrest of cells in the G 2 phase while D2 and D3 caused arrest in G 1 phase of the cell cycle. All compounds interfered with Akt activation, decreased XIAP expression leading to an increased cleavage of caspase-9, -3, PARP, increased Bax/Bcl2 ratio and caspase-3 activity. Conclusion: Findings suggest that benzopyran derivatives inhibit cellular proliferation via modulating ER-dependent classical and non-classical signaling mechanisms, interfere with Akt activation and induce apoptosis via intrinsic pathway in endometrial adenocarcinoma cells.",
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T1 - 2,3-Diaryl-2H-1-benzopyran derivatives interfere with classical and non-classical estrogen receptor signaling pathways, inhibit Akt activation and induce apoptosis in human endometrial cancer cells

AU - Fatima, Iram

AU - Chandra, V.

AU - Saxena, R.

AU - Manohar, M.

AU - Sanghani, Y.

AU - Hajela, K.

AU - Negi, M. P.S.

AU - Sankhwar, P. L.

AU - Jain, S. K.

AU - Dwivedi, A.

PY - 2012/1/2

Y1 - 2012/1/2

N2 - Objectives: The present study was undertaken to explore the mechanism of anti-proliferative action of benzopyran compound D1 (2-[piperidinoethoxyphenyl]-3-phenyl-2H-benzopyran) and its hydroxy-(D2) and methoxy-(D3) derivatives in Ishikawa and human primary endometrial adenocarcinoma cells. Methods: Transcriptional activation assays were performed using luciferase reporter system and cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The stage of cell cycle was determined by flow-cytometry and real time analysis of cyclinE1 and cdc2 genes. The apoptotic effects were measured by AnnexinV/PI staining and TUNEL. The expression of PCNA, cyclinD1, pAkt, XIAP, cleaved caspase-9, -3, PARP, Bax and Bcl2 were determined by immunoblotting. The caspase-3 activity and mitochondrial membrane potential were measured by colorimetric assay. Results: All three compounds inhibited E 2 -induced ERE- and AP-1-mediated transactivation and proliferation in endometrial adenocarcinoma cells dose-dependently. Compound D1 caused the arrest of cells in the G 2 phase while D2 and D3 caused arrest in G 1 phase of the cell cycle. All compounds interfered with Akt activation, decreased XIAP expression leading to an increased cleavage of caspase-9, -3, PARP, increased Bax/Bcl2 ratio and caspase-3 activity. Conclusion: Findings suggest that benzopyran derivatives inhibit cellular proliferation via modulating ER-dependent classical and non-classical signaling mechanisms, interfere with Akt activation and induce apoptosis via intrinsic pathway in endometrial adenocarcinoma cells.

AB - Objectives: The present study was undertaken to explore the mechanism of anti-proliferative action of benzopyran compound D1 (2-[piperidinoethoxyphenyl]-3-phenyl-2H-benzopyran) and its hydroxy-(D2) and methoxy-(D3) derivatives in Ishikawa and human primary endometrial adenocarcinoma cells. Methods: Transcriptional activation assays were performed using luciferase reporter system and cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The stage of cell cycle was determined by flow-cytometry and real time analysis of cyclinE1 and cdc2 genes. The apoptotic effects were measured by AnnexinV/PI staining and TUNEL. The expression of PCNA, cyclinD1, pAkt, XIAP, cleaved caspase-9, -3, PARP, Bax and Bcl2 were determined by immunoblotting. The caspase-3 activity and mitochondrial membrane potential were measured by colorimetric assay. Results: All three compounds inhibited E 2 -induced ERE- and AP-1-mediated transactivation and proliferation in endometrial adenocarcinoma cells dose-dependently. Compound D1 caused the arrest of cells in the G 2 phase while D2 and D3 caused arrest in G 1 phase of the cell cycle. All compounds interfered with Akt activation, decreased XIAP expression leading to an increased cleavage of caspase-9, -3, PARP, increased Bax/Bcl2 ratio and caspase-3 activity. Conclusion: Findings suggest that benzopyran derivatives inhibit cellular proliferation via modulating ER-dependent classical and non-classical signaling mechanisms, interfere with Akt activation and induce apoptosis via intrinsic pathway in endometrial adenocarcinoma cells.

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U2 - 10.1016/j.mce.2011.08.018

DO - 10.1016/j.mce.2011.08.018

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JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

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