Anti-tumorigenic action of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]- 2H-benzo(b)pyran

Evidence for involvement of GPR30/EGFR signaling pathway

V. Chandra, Iram Fatima, R. Saxena, M. K. Hussain, K. Hajela, P. Sankhwar, B. G. Roy, S. Chandna, A. Dwivedi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objective: The aim of the present study was to investigate the effect of non-steroidal, pure antiestrogenic benzopyran derivative i.e., 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran (K-1) on the growth of human endometrial cancer cells in vivo and in vitro and to elucidate its mechanism of action. Methods: Cell proliferation was assayed by measuring the incorporation of 5′-bromo-2′-deoxyuridine in Ishikawa and primary endometrial cancer cells. The expression of proliferation and apoptotic markers was analyzed by immunoblotting. The effect of K-1 on GPR30-regulated proteins was analyzed by ELISA and by immunoblotting. Nude mice bearing subcutaneous implanted-Ishikawa tumors, were treated for 14 days with K-1 (200 μg/kg body weight/day/orally). The proliferation markers, GPR30-regulated proteins and apoptotic markers were analyzed by immunoblotting in tumor xenograft. The apoptotic effect of compound K-1 was determined by TUNEL assay. Results: Compound K-1 inhibited proliferation of endometrial adenocarcinoma cells and decreased the expression of proliferation markers. It caused apoptosis by increasing the expression of apoptotic markers (NOXA, PUMAα) and reducing the expression of p-CREB and BclxL. Compound interfered with GPR30-regulated-EGFR activation, decreased p-ERK, p-c-jun, c-fos, cyclinD1 and c-myc expression. Treatment of tumor-bearing mice with K-1 resulted in a significant decrease in tumor volume and weight. Decreased expression of p-ERK and its downstream molecules and increased expression of apoptotic markers were observed in tumor in K-1 treated animals. Conclusion Findings suggest the potent inhibitory effect of compound K-1 on endometrial cancer cellular growth (in-vitro) and on tumor size (in-vivo) which is mediated at least, in part, by interference with GPR30-signaling.

Original languageEnglish (US)
Pages (from-to)433-442
Number of pages10
JournalGynecologic oncology
Volume129
Issue number2
DOIs
StatePublished - May 1 2013

Fingerprint

Endometrial Neoplasms
Immunoblotting
Neoplasms
Tumor Burden
Benzopyrans
In Situ Nick-End Labeling
Bromodeoxyuridine
Growth
Heterografts
Nude Mice
Proteins
Adenocarcinoma
Enzyme-Linked Immunosorbent Assay
Body Weight
Cell Proliferation
2-(piperidinoethoxyphenyl)-3-(4-hydroxyphenyl)-2H-benzo(b)pyran
Apoptosis
In Vitro Techniques
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Obstetrics and Gynecology

Cite this

Anti-tumorigenic action of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]- 2H-benzo(b)pyran : Evidence for involvement of GPR30/EGFR signaling pathway. / Chandra, V.; Fatima, Iram; Saxena, R.; Hussain, M. K.; Hajela, K.; Sankhwar, P.; Roy, B. G.; Chandna, S.; Dwivedi, A.

In: Gynecologic oncology, Vol. 129, No. 2, 01.05.2013, p. 433-442.

Research output: Contribution to journalArticle

Chandra, V. ; Fatima, Iram ; Saxena, R. ; Hussain, M. K. ; Hajela, K. ; Sankhwar, P. ; Roy, B. G. ; Chandna, S. ; Dwivedi, A. / Anti-tumorigenic action of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]- 2H-benzo(b)pyran : Evidence for involvement of GPR30/EGFR signaling pathway. In: Gynecologic oncology. 2013 ; Vol. 129, No. 2. pp. 433-442.
@article{30ee0f14b2bc4cd4913172bef7992389,
title = "Anti-tumorigenic action of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]- 2H-benzo(b)pyran: Evidence for involvement of GPR30/EGFR signaling pathway",
abstract = "Objective: The aim of the present study was to investigate the effect of non-steroidal, pure antiestrogenic benzopyran derivative i.e., 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran (K-1) on the growth of human endometrial cancer cells in vivo and in vitro and to elucidate its mechanism of action. Methods: Cell proliferation was assayed by measuring the incorporation of 5′-bromo-2′-deoxyuridine in Ishikawa and primary endometrial cancer cells. The expression of proliferation and apoptotic markers was analyzed by immunoblotting. The effect of K-1 on GPR30-regulated proteins was analyzed by ELISA and by immunoblotting. Nude mice bearing subcutaneous implanted-Ishikawa tumors, were treated for 14 days with K-1 (200 μg/kg body weight/day/orally). The proliferation markers, GPR30-regulated proteins and apoptotic markers were analyzed by immunoblotting in tumor xenograft. The apoptotic effect of compound K-1 was determined by TUNEL assay. Results: Compound K-1 inhibited proliferation of endometrial adenocarcinoma cells and decreased the expression of proliferation markers. It caused apoptosis by increasing the expression of apoptotic markers (NOXA, PUMAα) and reducing the expression of p-CREB and BclxL. Compound interfered with GPR30-regulated-EGFR activation, decreased p-ERK, p-c-jun, c-fos, cyclinD1 and c-myc expression. Treatment of tumor-bearing mice with K-1 resulted in a significant decrease in tumor volume and weight. Decreased expression of p-ERK and its downstream molecules and increased expression of apoptotic markers were observed in tumor in K-1 treated animals. Conclusion Findings suggest the potent inhibitory effect of compound K-1 on endometrial cancer cellular growth (in-vitro) and on tumor size (in-vivo) which is mediated at least, in part, by interference with GPR30-signaling.",
author = "V. Chandra and Iram Fatima and R. Saxena and Hussain, {M. K.} and K. Hajela and P. Sankhwar and Roy, {B. G.} and S. Chandna and A. Dwivedi",
year = "2013",
month = "5",
day = "1",
doi = "10.1016/j.ygyno.2013.02.005",
language = "English (US)",
volume = "129",
pages = "433--442",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Anti-tumorigenic action of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]- 2H-benzo(b)pyran

T2 - Evidence for involvement of GPR30/EGFR signaling pathway

AU - Chandra, V.

AU - Fatima, Iram

AU - Saxena, R.

AU - Hussain, M. K.

AU - Hajela, K.

AU - Sankhwar, P.

AU - Roy, B. G.

AU - Chandna, S.

AU - Dwivedi, A.

PY - 2013/5/1

Y1 - 2013/5/1

N2 - Objective: The aim of the present study was to investigate the effect of non-steroidal, pure antiestrogenic benzopyran derivative i.e., 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran (K-1) on the growth of human endometrial cancer cells in vivo and in vitro and to elucidate its mechanism of action. Methods: Cell proliferation was assayed by measuring the incorporation of 5′-bromo-2′-deoxyuridine in Ishikawa and primary endometrial cancer cells. The expression of proliferation and apoptotic markers was analyzed by immunoblotting. The effect of K-1 on GPR30-regulated proteins was analyzed by ELISA and by immunoblotting. Nude mice bearing subcutaneous implanted-Ishikawa tumors, were treated for 14 days with K-1 (200 μg/kg body weight/day/orally). The proliferation markers, GPR30-regulated proteins and apoptotic markers were analyzed by immunoblotting in tumor xenograft. The apoptotic effect of compound K-1 was determined by TUNEL assay. Results: Compound K-1 inhibited proliferation of endometrial adenocarcinoma cells and decreased the expression of proliferation markers. It caused apoptosis by increasing the expression of apoptotic markers (NOXA, PUMAα) and reducing the expression of p-CREB and BclxL. Compound interfered with GPR30-regulated-EGFR activation, decreased p-ERK, p-c-jun, c-fos, cyclinD1 and c-myc expression. Treatment of tumor-bearing mice with K-1 resulted in a significant decrease in tumor volume and weight. Decreased expression of p-ERK and its downstream molecules and increased expression of apoptotic markers were observed in tumor in K-1 treated animals. Conclusion Findings suggest the potent inhibitory effect of compound K-1 on endometrial cancer cellular growth (in-vitro) and on tumor size (in-vivo) which is mediated at least, in part, by interference with GPR30-signaling.

AB - Objective: The aim of the present study was to investigate the effect of non-steroidal, pure antiestrogenic benzopyran derivative i.e., 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran (K-1) on the growth of human endometrial cancer cells in vivo and in vitro and to elucidate its mechanism of action. Methods: Cell proliferation was assayed by measuring the incorporation of 5′-bromo-2′-deoxyuridine in Ishikawa and primary endometrial cancer cells. The expression of proliferation and apoptotic markers was analyzed by immunoblotting. The effect of K-1 on GPR30-regulated proteins was analyzed by ELISA and by immunoblotting. Nude mice bearing subcutaneous implanted-Ishikawa tumors, were treated for 14 days with K-1 (200 μg/kg body weight/day/orally). The proliferation markers, GPR30-regulated proteins and apoptotic markers were analyzed by immunoblotting in tumor xenograft. The apoptotic effect of compound K-1 was determined by TUNEL assay. Results: Compound K-1 inhibited proliferation of endometrial adenocarcinoma cells and decreased the expression of proliferation markers. It caused apoptosis by increasing the expression of apoptotic markers (NOXA, PUMAα) and reducing the expression of p-CREB and BclxL. Compound interfered with GPR30-regulated-EGFR activation, decreased p-ERK, p-c-jun, c-fos, cyclinD1 and c-myc expression. Treatment of tumor-bearing mice with K-1 resulted in a significant decrease in tumor volume and weight. Decreased expression of p-ERK and its downstream molecules and increased expression of apoptotic markers were observed in tumor in K-1 treated animals. Conclusion Findings suggest the potent inhibitory effect of compound K-1 on endometrial cancer cellular growth (in-vitro) and on tumor size (in-vivo) which is mediated at least, in part, by interference with GPR30-signaling.

UR - http://www.scopus.com/inward/record.url?scp=84876292049&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876292049&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2013.02.005

DO - 10.1016/j.ygyno.2013.02.005

M3 - Article

VL - 129

SP - 433

EP - 442

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 2

ER -