RRR-α-vitamin e succinate potentiates the antitumor effect of calcitriol in prostate cancer without overt side effects

Yi Yin, Jing Ni, Ming Chen, Yinglu Guo, Shuyuan Yeh

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Purpose: To determine the antitumor efficacy of using calcitriol combined with RRR-α-vitamin E succinate (VES) on prostate cancer. Experimental Design: The effects of VES or VES in combination with calcitriol on the calcitriol target genes were evaluated by Western blot and real-time PCR. The antiproliferation effect of the combination in prostate cancer cells was evaluated by the combination index method. The role of the vitamin D 3 receptor (VDR) in the enhanced antitumor effects of the combination was confirmed by small interfering RNA knockdown strategy. Xenograft-bearing mice were used to reaffirm the antitumor efficacy of this combination. Pathohistology analyses and expressions of VDR and its target genes were analyzed in untreated and treated tumors. Results: VES selectively increased VDR protein in different prostate cancer cells. Low closes of calcitriol combined with VES were significantly superior to the additive effect of individual treatments against prostate cancer cell proliferation. The expression of VDR target genes involved in antiproliferation were further sensitized in the presence of VES. Knockdown of VDR expression abolished the combination benefits in LNCaP and PC3 cells. Consistently, in prostate cancer xenograft models, VES enhanced the therapeutic efficacy of a tolerated dose of calcitriol yet without overt evidence of systemic toxicity and hypercalcemia. This notable in vivo effect was also accompanied by up-regulation of VDR target genes. Conclusions: Low-dose calcitriol combined with vitamin E analogue could be a solution to the calcemic side effect. The demonstration of superior antitumor activity of low-dose calcitriol plus VES provides the preclinical basis for developing a useful therapeutic strategy for prostate cancer.

Original languageEnglish (US)
Pages (from-to)190-200
Number of pages11
JournalClinical Cancer Research
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2009

Fingerprint

Calcitriol
Succinic Acid
Vitamin E
Vitamins
Prostatic Neoplasms
Calcitriol Receptors
Heterografts
Genes
Hypercalcemia
Small Interfering RNA
Real-Time Polymerase Chain Reaction
Research Design
Up-Regulation
Western Blotting
Cell Proliferation
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

RRR-α-vitamin e succinate potentiates the antitumor effect of calcitriol in prostate cancer without overt side effects. / Yin, Yi; Ni, Jing; Chen, Ming; Guo, Yinglu; Yeh, Shuyuan.

In: Clinical Cancer Research, Vol. 15, No. 1, 01.01.2009, p. 190-200.

Research output: Contribution to journalArticle

Yin, Yi ; Ni, Jing ; Chen, Ming ; Guo, Yinglu ; Yeh, Shuyuan. / RRR-α-vitamin e succinate potentiates the antitumor effect of calcitriol in prostate cancer without overt side effects. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 1. pp. 190-200.
@article{8b8b08e8db8f43cab670cfe3c471f26c,
title = "RRR-α-vitamin e succinate potentiates the antitumor effect of calcitriol in prostate cancer without overt side effects",
abstract = "Purpose: To determine the antitumor efficacy of using calcitriol combined with RRR-α-vitamin E succinate (VES) on prostate cancer. Experimental Design: The effects of VES or VES in combination with calcitriol on the calcitriol target genes were evaluated by Western blot and real-time PCR. The antiproliferation effect of the combination in prostate cancer cells was evaluated by the combination index method. The role of the vitamin D 3 receptor (VDR) in the enhanced antitumor effects of the combination was confirmed by small interfering RNA knockdown strategy. Xenograft-bearing mice were used to reaffirm the antitumor efficacy of this combination. Pathohistology analyses and expressions of VDR and its target genes were analyzed in untreated and treated tumors. Results: VES selectively increased VDR protein in different prostate cancer cells. Low closes of calcitriol combined with VES were significantly superior to the additive effect of individual treatments against prostate cancer cell proliferation. The expression of VDR target genes involved in antiproliferation were further sensitized in the presence of VES. Knockdown of VDR expression abolished the combination benefits in LNCaP and PC3 cells. Consistently, in prostate cancer xenograft models, VES enhanced the therapeutic efficacy of a tolerated dose of calcitriol yet without overt evidence of systemic toxicity and hypercalcemia. This notable in vivo effect was also accompanied by up-regulation of VDR target genes. Conclusions: Low-dose calcitriol combined with vitamin E analogue could be a solution to the calcemic side effect. The demonstration of superior antitumor activity of low-dose calcitriol plus VES provides the preclinical basis for developing a useful therapeutic strategy for prostate cancer.",
author = "Yi Yin and Jing Ni and Ming Chen and Yinglu Guo and Shuyuan Yeh",
year = "2009",
month = "1",
day = "1",
doi = "10.1158/1078-0432.CCR-08-0910",
language = "English (US)",
volume = "15",
pages = "190--200",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "1",

}

TY - JOUR

T1 - RRR-α-vitamin e succinate potentiates the antitumor effect of calcitriol in prostate cancer without overt side effects

AU - Yin, Yi

AU - Ni, Jing

AU - Chen, Ming

AU - Guo, Yinglu

AU - Yeh, Shuyuan

PY - 2009/1/1

Y1 - 2009/1/1

N2 - Purpose: To determine the antitumor efficacy of using calcitriol combined with RRR-α-vitamin E succinate (VES) on prostate cancer. Experimental Design: The effects of VES or VES in combination with calcitriol on the calcitriol target genes were evaluated by Western blot and real-time PCR. The antiproliferation effect of the combination in prostate cancer cells was evaluated by the combination index method. The role of the vitamin D 3 receptor (VDR) in the enhanced antitumor effects of the combination was confirmed by small interfering RNA knockdown strategy. Xenograft-bearing mice were used to reaffirm the antitumor efficacy of this combination. Pathohistology analyses and expressions of VDR and its target genes were analyzed in untreated and treated tumors. Results: VES selectively increased VDR protein in different prostate cancer cells. Low closes of calcitriol combined with VES were significantly superior to the additive effect of individual treatments against prostate cancer cell proliferation. The expression of VDR target genes involved in antiproliferation were further sensitized in the presence of VES. Knockdown of VDR expression abolished the combination benefits in LNCaP and PC3 cells. Consistently, in prostate cancer xenograft models, VES enhanced the therapeutic efficacy of a tolerated dose of calcitriol yet without overt evidence of systemic toxicity and hypercalcemia. This notable in vivo effect was also accompanied by up-regulation of VDR target genes. Conclusions: Low-dose calcitriol combined with vitamin E analogue could be a solution to the calcemic side effect. The demonstration of superior antitumor activity of low-dose calcitriol plus VES provides the preclinical basis for developing a useful therapeutic strategy for prostate cancer.

AB - Purpose: To determine the antitumor efficacy of using calcitriol combined with RRR-α-vitamin E succinate (VES) on prostate cancer. Experimental Design: The effects of VES or VES in combination with calcitriol on the calcitriol target genes were evaluated by Western blot and real-time PCR. The antiproliferation effect of the combination in prostate cancer cells was evaluated by the combination index method. The role of the vitamin D 3 receptor (VDR) in the enhanced antitumor effects of the combination was confirmed by small interfering RNA knockdown strategy. Xenograft-bearing mice were used to reaffirm the antitumor efficacy of this combination. Pathohistology analyses and expressions of VDR and its target genes were analyzed in untreated and treated tumors. Results: VES selectively increased VDR protein in different prostate cancer cells. Low closes of calcitriol combined with VES were significantly superior to the additive effect of individual treatments against prostate cancer cell proliferation. The expression of VDR target genes involved in antiproliferation were further sensitized in the presence of VES. Knockdown of VDR expression abolished the combination benefits in LNCaP and PC3 cells. Consistently, in prostate cancer xenograft models, VES enhanced the therapeutic efficacy of a tolerated dose of calcitriol yet without overt evidence of systemic toxicity and hypercalcemia. This notable in vivo effect was also accompanied by up-regulation of VDR target genes. Conclusions: Low-dose calcitriol combined with vitamin E analogue could be a solution to the calcemic side effect. The demonstration of superior antitumor activity of low-dose calcitriol plus VES provides the preclinical basis for developing a useful therapeutic strategy for prostate cancer.

UR - http://www.scopus.com/inward/record.url?scp=58849087664&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58849087664&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-08-0910

DO - 10.1158/1078-0432.CCR-08-0910

M3 - Article

C2 - 19118046

AN - SCOPUS:58849087664

VL - 15

SP - 190

EP - 200

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 1

ER -