Butanol fraction containing berberine or related compound from Nexrutine® inhibits NFκB signaling and induces apoptosis in prostate cancer cells

Sri Balasubashini Muralimanoharan, A. B. Kunnumakkara, Bhaskaran Shylesh, Kaustubh H. Kulkarni, Xu Haiyan, Hu Ming, Bharat B. Aggarwal, Ghosh Rita, Addanki P. Kumar

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

BACKGROUND. Epidemiological and laboratory studies support the hypothesis that several plant components influence prostate carcinogenesis and holds promise for disease prevention. Previously we reported that Nexrutine® (bark extract from Phellodendron amurense) inhibits proliferation of prostate cancer cells and prostate tumor development in the transgenic adenocarcinoma of mouse prostate (TRAMP) model through modulation of Akt signaling pathway. In the present investigation we conducted studies to further define the mechanism of action of Nexrutine® and to identify the active component associated with its biological activity. METHODS. Androgen-responsive, androgen-independent human prostate cancer cell lines and tissues from TRAMP mice fed Nexrutine® were used in these studies. Activity guided fractionation identified butanol fraction recapitulating the activities of Nexrutine® assessed by proliferation assays, apoptotic assays (DAPI and TUNEL staining), transient transfections, gel shift assays and Western blotting. In addition ultra-performance liquid chromatography (UPLC) of butanol fraction was used to identify active component of Nexrutine®. RESULTS. Butanol fraction recapitulated the activities of Nexrutine® in (i) inhibiting proliferation; (ii) inducing apoptosis; and (iii) modulating transcriptional activity of NFκB in prostate cancer cells. Our data also indicates that both Nexrutine® and butanol fraction modulates NFκB transcriptional activity by inhibiting IκBα phosphorylation. Expression of p65 and phosphorylated IκBα are high in tumors from TRAMP mice. In contrast dietary administration of Nexrutine® reduced expression of p65 and phosphorylated IκBα in prostate from TRAMP mice. In addition using UPLC, we have identified berberine or closely related compound in the butanol fraction. CONCLUSION. The results suggest that berberine or closely related component of butanol fraction may be responsible for the observed biological activities and induce apoptosis in prostate cancer cells by targeting critical cell survival signaling pathways both in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)494-504
Number of pages11
JournalProstate
Volume69
Issue number5
DOIs
StatePublished - Apr 1 2009

Fingerprint

Berberine
Butanols
Prostatic Neoplasms
Apoptosis
Prostate
Transgenic Mice
Adenocarcinoma
Liquid Chromatography
Androgens
Phellodendron
Plant Structures
Nexrutine
In Situ Nick-End Labeling
Transfection
Epidemiologic Studies
Neoplasms
Cell Survival
Carcinogenesis
Western Blotting
Gels

Keywords

  • Apoptosis
  • Fractionation
  • Nexrutine

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Urology

Cite this

Muralimanoharan, S. B., Kunnumakkara, A. B., Shylesh, B., Kulkarni, K. H., Haiyan, X., Ming, H., ... Kumar, A. P. (2009). Butanol fraction containing berberine or related compound from Nexrutine® inhibits NFκB signaling and induces apoptosis in prostate cancer cells. Prostate, 69(5), 494-504. https://doi.org/10.1002/pros.20899

Butanol fraction containing berberine or related compound from Nexrutine® inhibits NFκB signaling and induces apoptosis in prostate cancer cells. / Muralimanoharan, Sri Balasubashini; Kunnumakkara, A. B.; Shylesh, Bhaskaran; Kulkarni, Kaustubh H.; Haiyan, Xu; Ming, Hu; Aggarwal, Bharat B.; Rita, Ghosh; Kumar, Addanki P.

In: Prostate, Vol. 69, No. 5, 01.04.2009, p. 494-504.

Research output: Contribution to journalArticle

Muralimanoharan, SB, Kunnumakkara, AB, Shylesh, B, Kulkarni, KH, Haiyan, X, Ming, H, Aggarwal, BB, Rita, G & Kumar, AP 2009, 'Butanol fraction containing berberine or related compound from Nexrutine® inhibits NFκB signaling and induces apoptosis in prostate cancer cells', Prostate, vol. 69, no. 5, pp. 494-504. https://doi.org/10.1002/pros.20899
Muralimanoharan, Sri Balasubashini ; Kunnumakkara, A. B. ; Shylesh, Bhaskaran ; Kulkarni, Kaustubh H. ; Haiyan, Xu ; Ming, Hu ; Aggarwal, Bharat B. ; Rita, Ghosh ; Kumar, Addanki P. / Butanol fraction containing berberine or related compound from Nexrutine® inhibits NFκB signaling and induces apoptosis in prostate cancer cells. In: Prostate. 2009 ; Vol. 69, No. 5. pp. 494-504.
@article{e2faf50bbcec49d0893e67c709c610f7,
title = "Butanol fraction containing berberine or related compound from Nexrutine{\circledR} inhibits NFκB signaling and induces apoptosis in prostate cancer cells",
abstract = "BACKGROUND. Epidemiological and laboratory studies support the hypothesis that several plant components influence prostate carcinogenesis and holds promise for disease prevention. Previously we reported that Nexrutine{\circledR} (bark extract from Phellodendron amurense) inhibits proliferation of prostate cancer cells and prostate tumor development in the transgenic adenocarcinoma of mouse prostate (TRAMP) model through modulation of Akt signaling pathway. In the present investigation we conducted studies to further define the mechanism of action of Nexrutine{\circledR} and to identify the active component associated with its biological activity. METHODS. Androgen-responsive, androgen-independent human prostate cancer cell lines and tissues from TRAMP mice fed Nexrutine{\circledR} were used in these studies. Activity guided fractionation identified butanol fraction recapitulating the activities of Nexrutine{\circledR} assessed by proliferation assays, apoptotic assays (DAPI and TUNEL staining), transient transfections, gel shift assays and Western blotting. In addition ultra-performance liquid chromatography (UPLC) of butanol fraction was used to identify active component of Nexrutine{\circledR}. RESULTS. Butanol fraction recapitulated the activities of Nexrutine{\circledR} in (i) inhibiting proliferation; (ii) inducing apoptosis; and (iii) modulating transcriptional activity of NFκB in prostate cancer cells. Our data also indicates that both Nexrutine{\circledR} and butanol fraction modulates NFκB transcriptional activity by inhibiting IκBα phosphorylation. Expression of p65 and phosphorylated IκBα are high in tumors from TRAMP mice. In contrast dietary administration of Nexrutine{\circledR} reduced expression of p65 and phosphorylated IκBα in prostate from TRAMP mice. In addition using UPLC, we have identified berberine or closely related compound in the butanol fraction. CONCLUSION. The results suggest that berberine or closely related component of butanol fraction may be responsible for the observed biological activities and induce apoptosis in prostate cancer cells by targeting critical cell survival signaling pathways both in vitro and in vivo.",
keywords = "Apoptosis, Fractionation, Nexrutine",
author = "Muralimanoharan, {Sri Balasubashini} and Kunnumakkara, {A. B.} and Bhaskaran Shylesh and Kulkarni, {Kaustubh H.} and Xu Haiyan and Hu Ming and Aggarwal, {Bharat B.} and Ghosh Rita and Kumar, {Addanki P.}",
year = "2009",
month = "4",
day = "1",
doi = "10.1002/pros.20899",
language = "English (US)",
volume = "69",
pages = "494--504",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - Butanol fraction containing berberine or related compound from Nexrutine® inhibits NFκB signaling and induces apoptosis in prostate cancer cells

AU - Muralimanoharan, Sri Balasubashini

AU - Kunnumakkara, A. B.

AU - Shylesh, Bhaskaran

AU - Kulkarni, Kaustubh H.

AU - Haiyan, Xu

AU - Ming, Hu

AU - Aggarwal, Bharat B.

AU - Rita, Ghosh

AU - Kumar, Addanki P.

PY - 2009/4/1

Y1 - 2009/4/1

N2 - BACKGROUND. Epidemiological and laboratory studies support the hypothesis that several plant components influence prostate carcinogenesis and holds promise for disease prevention. Previously we reported that Nexrutine® (bark extract from Phellodendron amurense) inhibits proliferation of prostate cancer cells and prostate tumor development in the transgenic adenocarcinoma of mouse prostate (TRAMP) model through modulation of Akt signaling pathway. In the present investigation we conducted studies to further define the mechanism of action of Nexrutine® and to identify the active component associated with its biological activity. METHODS. Androgen-responsive, androgen-independent human prostate cancer cell lines and tissues from TRAMP mice fed Nexrutine® were used in these studies. Activity guided fractionation identified butanol fraction recapitulating the activities of Nexrutine® assessed by proliferation assays, apoptotic assays (DAPI and TUNEL staining), transient transfections, gel shift assays and Western blotting. In addition ultra-performance liquid chromatography (UPLC) of butanol fraction was used to identify active component of Nexrutine®. RESULTS. Butanol fraction recapitulated the activities of Nexrutine® in (i) inhibiting proliferation; (ii) inducing apoptosis; and (iii) modulating transcriptional activity of NFκB in prostate cancer cells. Our data also indicates that both Nexrutine® and butanol fraction modulates NFκB transcriptional activity by inhibiting IκBα phosphorylation. Expression of p65 and phosphorylated IκBα are high in tumors from TRAMP mice. In contrast dietary administration of Nexrutine® reduced expression of p65 and phosphorylated IκBα in prostate from TRAMP mice. In addition using UPLC, we have identified berberine or closely related compound in the butanol fraction. CONCLUSION. The results suggest that berberine or closely related component of butanol fraction may be responsible for the observed biological activities and induce apoptosis in prostate cancer cells by targeting critical cell survival signaling pathways both in vitro and in vivo.

AB - BACKGROUND. Epidemiological and laboratory studies support the hypothesis that several plant components influence prostate carcinogenesis and holds promise for disease prevention. Previously we reported that Nexrutine® (bark extract from Phellodendron amurense) inhibits proliferation of prostate cancer cells and prostate tumor development in the transgenic adenocarcinoma of mouse prostate (TRAMP) model through modulation of Akt signaling pathway. In the present investigation we conducted studies to further define the mechanism of action of Nexrutine® and to identify the active component associated with its biological activity. METHODS. Androgen-responsive, androgen-independent human prostate cancer cell lines and tissues from TRAMP mice fed Nexrutine® were used in these studies. Activity guided fractionation identified butanol fraction recapitulating the activities of Nexrutine® assessed by proliferation assays, apoptotic assays (DAPI and TUNEL staining), transient transfections, gel shift assays and Western blotting. In addition ultra-performance liquid chromatography (UPLC) of butanol fraction was used to identify active component of Nexrutine®. RESULTS. Butanol fraction recapitulated the activities of Nexrutine® in (i) inhibiting proliferation; (ii) inducing apoptosis; and (iii) modulating transcriptional activity of NFκB in prostate cancer cells. Our data also indicates that both Nexrutine® and butanol fraction modulates NFκB transcriptional activity by inhibiting IκBα phosphorylation. Expression of p65 and phosphorylated IκBα are high in tumors from TRAMP mice. In contrast dietary administration of Nexrutine® reduced expression of p65 and phosphorylated IκBα in prostate from TRAMP mice. In addition using UPLC, we have identified berberine or closely related compound in the butanol fraction. CONCLUSION. The results suggest that berberine or closely related component of butanol fraction may be responsible for the observed biological activities and induce apoptosis in prostate cancer cells by targeting critical cell survival signaling pathways both in vitro and in vivo.

KW - Apoptosis

KW - Fractionation

KW - Nexrutine

UR - http://www.scopus.com/inward/record.url?scp=61949090849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61949090849&partnerID=8YFLogxK

U2 - 10.1002/pros.20899

DO - 10.1002/pros.20899

M3 - Article

C2 - 19107816

AN - SCOPUS:61949090849

VL - 69

SP - 494

EP - 504

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 5

ER -