Identification of drug candidate against prostate cancer from the aspect of somatic cell reprogramming

Takeo Kosaka, Go Nagamatsu, Shigeru Saito, Mototsugu Oya, Toshio Suda, Katsuhisa Horimoto

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Considering the similarities between the transcriptional programming involved in cancer progression and somatic cell reprogramming, we tried to identify drugs that would be effective against malignant cancers. We used the early transposon Oct4 and Sox2 enhancer (EOS) system to select human prostate cancer (PCA) cells expressing high levels of OCT4. Patients with metastatic castration-resistant PCA that does not respond to treatment with docetaxel have few therapeutic options. The OCT4-expressing PCA cells selected using the EOS system showed increased tumorigenicity and high resistance to docetaxel, both in vitro and in vivo. By using their gene expression data, expression signature-based prediction for compound candidates identified an antiviral drug, ribavirin, as a conversion modulator from drug resistance to sensitivity. Treatment of PCA cells with ribavirin decreased their resistance against treatment with docetaxel. This indicated that ribavirin reversed the gene expression, including that of humoral factors, in the OCT4-expressing PCA cells selected using the EOS system. Thereby, ribavirin increased the efficacy of docetaxel for cancer cells. We propose a novel cell reprogramming approach, named drug efficacy reprogramming, as a new model for identifying candidate antitumor drugs.

Original languageEnglish
Pages (from-to)1017-1026
Number of pages10
JournalCancer Science
Volume104
Issue number8
DOIs
Publication statusPublished - 2013 Aug

Fingerprint

docetaxel
Ribavirin
Prostatic Neoplasms
Pharmaceutical Preparations
Gene Expression
Neoplasms
Castration
Therapeutics
Drug Resistance
Antineoplastic Agents
Antiviral Agents
Cellular Reprogramming

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Identification of drug candidate against prostate cancer from the aspect of somatic cell reprogramming. / Kosaka, Takeo; Nagamatsu, Go; Saito, Shigeru; Oya, Mototsugu; Suda, Toshio; Horimoto, Katsuhisa.

In: Cancer Science, Vol. 104, No. 8, 08.2013, p. 1017-1026.

Research output: Contribution to journalArticle

Kosaka, Takeo ; Nagamatsu, Go ; Saito, Shigeru ; Oya, Mototsugu ; Suda, Toshio ; Horimoto, Katsuhisa. / Identification of drug candidate against prostate cancer from the aspect of somatic cell reprogramming. In: Cancer Science. 2013 ; Vol. 104, No. 8. pp. 1017-1026.
@article{f3971bc0c9ee4d5a8c7cd3817921f126,
title = "Identification of drug candidate against prostate cancer from the aspect of somatic cell reprogramming",
abstract = "Considering the similarities between the transcriptional programming involved in cancer progression and somatic cell reprogramming, we tried to identify drugs that would be effective against malignant cancers. We used the early transposon Oct4 and Sox2 enhancer (EOS) system to select human prostate cancer (PCA) cells expressing high levels of OCT4. Patients with metastatic castration-resistant PCA that does not respond to treatment with docetaxel have few therapeutic options. The OCT4-expressing PCA cells selected using the EOS system showed increased tumorigenicity and high resistance to docetaxel, both in vitro and in vivo. By using their gene expression data, expression signature-based prediction for compound candidates identified an antiviral drug, ribavirin, as a conversion modulator from drug resistance to sensitivity. Treatment of PCA cells with ribavirin decreased their resistance against treatment with docetaxel. This indicated that ribavirin reversed the gene expression, including that of humoral factors, in the OCT4-expressing PCA cells selected using the EOS system. Thereby, ribavirin increased the efficacy of docetaxel for cancer cells. We propose a novel cell reprogramming approach, named drug efficacy reprogramming, as a new model for identifying candidate antitumor drugs.",
author = "Takeo Kosaka and Go Nagamatsu and Shigeru Saito and Mototsugu Oya and Toshio Suda and Katsuhisa Horimoto",
year = "2013",
month = "8",
doi = "10.1111/cas.12183",
language = "English",
volume = "104",
pages = "1017--1026",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Identification of drug candidate against prostate cancer from the aspect of somatic cell reprogramming

AU - Kosaka, Takeo

AU - Nagamatsu, Go

AU - Saito, Shigeru

AU - Oya, Mototsugu

AU - Suda, Toshio

AU - Horimoto, Katsuhisa

PY - 2013/8

Y1 - 2013/8

N2 - Considering the similarities between the transcriptional programming involved in cancer progression and somatic cell reprogramming, we tried to identify drugs that would be effective against malignant cancers. We used the early transposon Oct4 and Sox2 enhancer (EOS) system to select human prostate cancer (PCA) cells expressing high levels of OCT4. Patients with metastatic castration-resistant PCA that does not respond to treatment with docetaxel have few therapeutic options. The OCT4-expressing PCA cells selected using the EOS system showed increased tumorigenicity and high resistance to docetaxel, both in vitro and in vivo. By using their gene expression data, expression signature-based prediction for compound candidates identified an antiviral drug, ribavirin, as a conversion modulator from drug resistance to sensitivity. Treatment of PCA cells with ribavirin decreased their resistance against treatment with docetaxel. This indicated that ribavirin reversed the gene expression, including that of humoral factors, in the OCT4-expressing PCA cells selected using the EOS system. Thereby, ribavirin increased the efficacy of docetaxel for cancer cells. We propose a novel cell reprogramming approach, named drug efficacy reprogramming, as a new model for identifying candidate antitumor drugs.

AB - Considering the similarities between the transcriptional programming involved in cancer progression and somatic cell reprogramming, we tried to identify drugs that would be effective against malignant cancers. We used the early transposon Oct4 and Sox2 enhancer (EOS) system to select human prostate cancer (PCA) cells expressing high levels of OCT4. Patients with metastatic castration-resistant PCA that does not respond to treatment with docetaxel have few therapeutic options. The OCT4-expressing PCA cells selected using the EOS system showed increased tumorigenicity and high resistance to docetaxel, both in vitro and in vivo. By using their gene expression data, expression signature-based prediction for compound candidates identified an antiviral drug, ribavirin, as a conversion modulator from drug resistance to sensitivity. Treatment of PCA cells with ribavirin decreased their resistance against treatment with docetaxel. This indicated that ribavirin reversed the gene expression, including that of humoral factors, in the OCT4-expressing PCA cells selected using the EOS system. Thereby, ribavirin increased the efficacy of docetaxel for cancer cells. We propose a novel cell reprogramming approach, named drug efficacy reprogramming, as a new model for identifying candidate antitumor drugs.

UR - http://www.scopus.com/inward/record.url?scp=84881101720&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881101720&partnerID=8YFLogxK

U2 - 10.1111/cas.12183

DO - 10.1111/cas.12183

M3 - Article

VL - 104

SP - 1017

EP - 1026

JO - Cancer Science

JF - Cancer Science

SN - 1347-9032

IS - 8

ER -