20 Citations (Scopus)

Abstract

5,16-dihydrotanshinone I (DHTS) is extracted from Salvia miltiorrhiza Bunge (tanshen root) and was found to be the most effective compound of tanshen extracts against breast cancer cells in our previous studies. However, whether DHTS can induce apoptosis through an endoplasmic reticular (ER) stress pathway was examined herein. In this study, we found that DHTS significantly inhibited the proliferation of human prostate DU145 carcinoma cells and induced apoptosis. DHTS was able to induce ER stress as evidenced by the upregulation of glucose regulation protein 78 (GRP78/Bip) and CAAT/enhancer binding protein homologous protein/growth arrest- and DNA damage-inducible gene 153 (CHOP/GADD153), as well as increases in phosphorylated eukaryotic initiation factor 2 (eIF2), c-jun N-terminal kinase (JNK), and X-box-binding protein 1 (XBP1) mRNA splicing forms. DHTS treatment also caused significant accumulation of polyubiquitinated proteins and hypoxia-inducible factor (HIF)-1, indicating that DHTS might be a proteasome inhibitor that is known to induce ER stress or enhance apoptosis caused by the classic ER stress-dependent mechanism. Moreover, DHTS-induced apoptosis was reversed by salubrinal, an ER stress inhibitor. Results suggest that DHTS can induce apoptosis of prostate carcinoma cells via induction of ER stress and/or inhibition of proteasome activity, and may have therapeutic potential for prostate cancer patients.

Original languageEnglish
Article number865435
JournalEvidence-based Complementary and Alternative Medicine
Volume2011
DOIs
Publication statusPublished - 2011

Fingerprint

Salvia miltiorrhiza
Prostate
Apoptosis
Carcinoma
Transcription Factor CHOP
Eukaryotic Initiation Factor-2
CCAAT-Enhancer-Binding Proteins
Hypoxia-Inducible Factor 1
Proteasome Inhibitors
JNK Mitogen-Activated Protein Kinases
Proteasome Endopeptidase Complex
Prostatic Neoplasms
Proteins
Up-Regulation
15,16-dihydrotanshinone I
Breast Neoplasms
Glucose
Messenger RNA
Therapeutics
Genes

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

@article{2a5220136a65476788d0bd85a04de187,
title = "15,16-Dihydrotanshinone I, a compound of salvia miltiorrhiza bunge, induces apoptosis through inducing endoplasmic reticular stress in human prostate carcinoma cells",
abstract = "5,16-dihydrotanshinone I (DHTS) is extracted from Salvia miltiorrhiza Bunge (tanshen root) and was found to be the most effective compound of tanshen extracts against breast cancer cells in our previous studies. However, whether DHTS can induce apoptosis through an endoplasmic reticular (ER) stress pathway was examined herein. In this study, we found that DHTS significantly inhibited the proliferation of human prostate DU145 carcinoma cells and induced apoptosis. DHTS was able to induce ER stress as evidenced by the upregulation of glucose regulation protein 78 (GRP78/Bip) and CAAT/enhancer binding protein homologous protein/growth arrest- and DNA damage-inducible gene 153 (CHOP/GADD153), as well as increases in phosphorylated eukaryotic initiation factor 2 (eIF2), c-jun N-terminal kinase (JNK), and X-box-binding protein 1 (XBP1) mRNA splicing forms. DHTS treatment also caused significant accumulation of polyubiquitinated proteins and hypoxia-inducible factor (HIF)-1, indicating that DHTS might be a proteasome inhibitor that is known to induce ER stress or enhance apoptosis caused by the classic ER stress-dependent mechanism. Moreover, DHTS-induced apoptosis was reversed by salubrinal, an ER stress inhibitor. Results suggest that DHTS can induce apoptosis of prostate carcinoma cells via induction of ER stress and/or inhibition of proteasome activity, and may have therapeutic potential for prostate cancer patients.",
author = "Liang, {Yu Chih} and Chuang, {Mao Te} and Ho, {Feng Ming} and Wu, {Chien Chih} and Zhuang, {Shao Yu} and Lin, {Shyr Yi} and Suk, {Fat Moon}",
year = "2011",
doi = "10.1155/2011/865435",
language = "English",
volume = "2011",
journal = "Evidence-based Complementary and Alternative Medicine",
issn = "1741-427X",
publisher = "Hindawi Publishing Corporation",

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TY - JOUR

T1 - 15,16-Dihydrotanshinone I, a compound of salvia miltiorrhiza bunge, induces apoptosis through inducing endoplasmic reticular stress in human prostate carcinoma cells

AU - Liang, Yu Chih

AU - Chuang, Mao Te

AU - Ho, Feng Ming

AU - Wu, Chien Chih

AU - Zhuang, Shao Yu

AU - Lin, Shyr Yi

AU - Suk, Fat Moon

PY - 2011

Y1 - 2011

N2 - 5,16-dihydrotanshinone I (DHTS) is extracted from Salvia miltiorrhiza Bunge (tanshen root) and was found to be the most effective compound of tanshen extracts against breast cancer cells in our previous studies. However, whether DHTS can induce apoptosis through an endoplasmic reticular (ER) stress pathway was examined herein. In this study, we found that DHTS significantly inhibited the proliferation of human prostate DU145 carcinoma cells and induced apoptosis. DHTS was able to induce ER stress as evidenced by the upregulation of glucose regulation protein 78 (GRP78/Bip) and CAAT/enhancer binding protein homologous protein/growth arrest- and DNA damage-inducible gene 153 (CHOP/GADD153), as well as increases in phosphorylated eukaryotic initiation factor 2 (eIF2), c-jun N-terminal kinase (JNK), and X-box-binding protein 1 (XBP1) mRNA splicing forms. DHTS treatment also caused significant accumulation of polyubiquitinated proteins and hypoxia-inducible factor (HIF)-1, indicating that DHTS might be a proteasome inhibitor that is known to induce ER stress or enhance apoptosis caused by the classic ER stress-dependent mechanism. Moreover, DHTS-induced apoptosis was reversed by salubrinal, an ER stress inhibitor. Results suggest that DHTS can induce apoptosis of prostate carcinoma cells via induction of ER stress and/or inhibition of proteasome activity, and may have therapeutic potential for prostate cancer patients.

AB - 5,16-dihydrotanshinone I (DHTS) is extracted from Salvia miltiorrhiza Bunge (tanshen root) and was found to be the most effective compound of tanshen extracts against breast cancer cells in our previous studies. However, whether DHTS can induce apoptosis through an endoplasmic reticular (ER) stress pathway was examined herein. In this study, we found that DHTS significantly inhibited the proliferation of human prostate DU145 carcinoma cells and induced apoptosis. DHTS was able to induce ER stress as evidenced by the upregulation of glucose regulation protein 78 (GRP78/Bip) and CAAT/enhancer binding protein homologous protein/growth arrest- and DNA damage-inducible gene 153 (CHOP/GADD153), as well as increases in phosphorylated eukaryotic initiation factor 2 (eIF2), c-jun N-terminal kinase (JNK), and X-box-binding protein 1 (XBP1) mRNA splicing forms. DHTS treatment also caused significant accumulation of polyubiquitinated proteins and hypoxia-inducible factor (HIF)-1, indicating that DHTS might be a proteasome inhibitor that is known to induce ER stress or enhance apoptosis caused by the classic ER stress-dependent mechanism. Moreover, DHTS-induced apoptosis was reversed by salubrinal, an ER stress inhibitor. Results suggest that DHTS can induce apoptosis of prostate carcinoma cells via induction of ER stress and/or inhibition of proteasome activity, and may have therapeutic potential for prostate cancer patients.

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