Ovatodiolide suppresses nasopharyngeal cancer by targeting stem cell-like population, inducing apoptosis, inhibiting EMT and dysregulating JAK/STAT signaling pathway

Shao Cheng Liu, Chih Ming Huang, Oluwaseun Adebayo Bamodu, Chun Shu Lin, Bing Lan Liu, Yew Min Tzeng, Jo Ting Tsai, Wei Hwa Lee, Tsung Ming Chen

研究成果: 雜誌貢獻文章

5 引文 (Scopus)

摘要

Background: Treatment for metastatic nasopharyngeal carcinoma (NPC) is challenging. Till now, a truly effective chemotherapy regimen for NPC has not yet been identified. These clinical observations prompted us to investigate a potential drug as alternative option for treating. Purpose: This study evaluated the inhibitory effects of Ovatodiolide (Ova), on tumorigenic and cancer stem cell characteristics of NPC cells. Methods: Two NPC cell lines (NPC-BM1 and NPC-BM2) were used to examine the anticancer effects of Ova and the molecular mechanism underlying these activities by using sulforhodamine B cytotoxicity assay, western blot, immunofluorescence, migration, colony and tumorsphere formation assays. Results: Ova significantly inhibited the viability of BM1 and BM2 cells, downregulated Bcl-xL and Puma, and upregulated Bax/Bad expression levels. Ova dose-dependent suppressed migratory/invasive potential of NPC cells, and reduced ability to form colonies. Ova-induced apoptosis correlated with increased Bax/Bcl-xL ratio while NPC motility and colony formation inhibition were associated with reduced expression of p-FAK, p-PXN, F-actin, and Slug proteins and increased E-cadherin. Furthermore, ova inhibited NPC tumorsphere formation, associated with decreased SOX2, OCT4 and JAK-STAT signaling pathway. Ova also attenuated NPC stem cell tumorigenicity, inhibited tumor growth, and enhanced the sensitivity of NPC cells to cisplatin treatment, in vivo. Conclusions: Our results demonstrated the anticancer efficacy of Ova in NPC and its potential as a putative inhibitor of JAK2 and STAT3, which are essential in tumorigenesis of NPC. Further development of Ova is encouraged.
原文英語
頁(從 - 到)269-278
頁數10
期刊Phytomedicine
56
DOIs
出版狀態已發佈 - 三月 15 2019

指紋

Nasopharyngeal Neoplasms
Neoplastic Stem Cells
Apoptosis
Population
lissamine rhodamine B
Nasopharyngeal carcinoma
ovatodiolide
Puma
Gastropoda
Cadherins
Cisplatin

Keywords

  • Cancer stem cell
  • Chemoresistance
  • JAK-STAT pathway
  • Nasopharyngeal carcinoma
  • Ovatodiolide

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine

引用此文

@article{698cd1fb965340a49da38e35cbe4676c,
title = "Ovatodiolide suppresses nasopharyngeal cancer by targeting stem cell-like population, inducing apoptosis, inhibiting EMT and dysregulating JAK/STAT signaling pathway",
abstract = "Background: Treatment for metastatic nasopharyngeal carcinoma (NPC) is challenging. Till now, a truly effective chemotherapy regimen for NPC has not yet been identified. These clinical observations prompted us to investigate a potential drug as alternative option for treating. Purpose: This study evaluated the inhibitory effects of Ovatodiolide (Ova), on tumorigenic and cancer stem cell characteristics of NPC cells. Methods: Two NPC cell lines (NPC-BM1 and NPC-BM2) were used to examine the anticancer effects of Ova and the molecular mechanism underlying these activities by using sulforhodamine B cytotoxicity assay, western blot, immunofluorescence, migration, colony and tumorsphere formation assays. Results: Ova significantly inhibited the viability of BM1 and BM2 cells, downregulated Bcl-xL and Puma, and upregulated Bax/Bad expression levels. Ova dose-dependent suppressed migratory/invasive potential of NPC cells, and reduced ability to form colonies. Ova-induced apoptosis correlated with increased Bax/Bcl-xL ratio while NPC motility and colony formation inhibition were associated with reduced expression of p-FAK, p-PXN, F-actin, and Slug proteins and increased E-cadherin. Furthermore, ova inhibited NPC tumorsphere formation, associated with decreased SOX2, OCT4 and JAK-STAT signaling pathway. Ova also attenuated NPC stem cell tumorigenicity, inhibited tumor growth, and enhanced the sensitivity of NPC cells to cisplatin treatment, in vivo. Conclusions: Our results demonstrated the anticancer efficacy of Ova in NPC and its potential as a putative inhibitor of JAK2 and STAT3, which are essential in tumorigenesis of NPC. Further development of Ova is encouraged.",
keywords = "Cancer stem cell, Chemoresistance, JAK-STAT pathway, Nasopharyngeal carcinoma, Ovatodiolide, Cancer stem cell, Chemoresistance, JAK-STAT pathway, Nasopharyngeal carcinoma, Ovatodiolide",
author = "Liu, {Shao Cheng} and Huang, {Chih Ming} and Bamodu, {Oluwaseun Adebayo} and Lin, {Chun Shu} and Liu, {Bing Lan} and Tzeng, {Yew Min} and Tsai, {Jo Ting} and Lee, {Wei Hwa} and Chen, {Tsung Ming}",
year = "2019",
month = "3",
day = "15",
doi = "10.1016/j.phymed.2018.05.007",
language = "English",
volume = "56",
pages = "269--278",
journal = "Phytomedicine",
issn = "0944-7113",
publisher = "Urban und Fischer Verlag Jena",

}

TY - JOUR

T1 - Ovatodiolide suppresses nasopharyngeal cancer by targeting stem cell-like population, inducing apoptosis, inhibiting EMT and dysregulating JAK/STAT signaling pathway

AU - Liu, Shao Cheng

AU - Huang, Chih Ming

AU - Bamodu, Oluwaseun Adebayo

AU - Lin, Chun Shu

AU - Liu, Bing Lan

AU - Tzeng, Yew Min

AU - Tsai, Jo Ting

AU - Lee, Wei Hwa

AU - Chen, Tsung Ming

PY - 2019/3/15

Y1 - 2019/3/15

N2 - Background: Treatment for metastatic nasopharyngeal carcinoma (NPC) is challenging. Till now, a truly effective chemotherapy regimen for NPC has not yet been identified. These clinical observations prompted us to investigate a potential drug as alternative option for treating. Purpose: This study evaluated the inhibitory effects of Ovatodiolide (Ova), on tumorigenic and cancer stem cell characteristics of NPC cells. Methods: Two NPC cell lines (NPC-BM1 and NPC-BM2) were used to examine the anticancer effects of Ova and the molecular mechanism underlying these activities by using sulforhodamine B cytotoxicity assay, western blot, immunofluorescence, migration, colony and tumorsphere formation assays. Results: Ova significantly inhibited the viability of BM1 and BM2 cells, downregulated Bcl-xL and Puma, and upregulated Bax/Bad expression levels. Ova dose-dependent suppressed migratory/invasive potential of NPC cells, and reduced ability to form colonies. Ova-induced apoptosis correlated with increased Bax/Bcl-xL ratio while NPC motility and colony formation inhibition were associated with reduced expression of p-FAK, p-PXN, F-actin, and Slug proteins and increased E-cadherin. Furthermore, ova inhibited NPC tumorsphere formation, associated with decreased SOX2, OCT4 and JAK-STAT signaling pathway. Ova also attenuated NPC stem cell tumorigenicity, inhibited tumor growth, and enhanced the sensitivity of NPC cells to cisplatin treatment, in vivo. Conclusions: Our results demonstrated the anticancer efficacy of Ova in NPC and its potential as a putative inhibitor of JAK2 and STAT3, which are essential in tumorigenesis of NPC. Further development of Ova is encouraged.

AB - Background: Treatment for metastatic nasopharyngeal carcinoma (NPC) is challenging. Till now, a truly effective chemotherapy regimen for NPC has not yet been identified. These clinical observations prompted us to investigate a potential drug as alternative option for treating. Purpose: This study evaluated the inhibitory effects of Ovatodiolide (Ova), on tumorigenic and cancer stem cell characteristics of NPC cells. Methods: Two NPC cell lines (NPC-BM1 and NPC-BM2) were used to examine the anticancer effects of Ova and the molecular mechanism underlying these activities by using sulforhodamine B cytotoxicity assay, western blot, immunofluorescence, migration, colony and tumorsphere formation assays. Results: Ova significantly inhibited the viability of BM1 and BM2 cells, downregulated Bcl-xL and Puma, and upregulated Bax/Bad expression levels. Ova dose-dependent suppressed migratory/invasive potential of NPC cells, and reduced ability to form colonies. Ova-induced apoptosis correlated with increased Bax/Bcl-xL ratio while NPC motility and colony formation inhibition were associated with reduced expression of p-FAK, p-PXN, F-actin, and Slug proteins and increased E-cadherin. Furthermore, ova inhibited NPC tumorsphere formation, associated with decreased SOX2, OCT4 and JAK-STAT signaling pathway. Ova also attenuated NPC stem cell tumorigenicity, inhibited tumor growth, and enhanced the sensitivity of NPC cells to cisplatin treatment, in vivo. Conclusions: Our results demonstrated the anticancer efficacy of Ova in NPC and its potential as a putative inhibitor of JAK2 and STAT3, which are essential in tumorigenesis of NPC. Further development of Ova is encouraged.

KW - Cancer stem cell

KW - Chemoresistance

KW - JAK-STAT pathway

KW - Nasopharyngeal carcinoma

KW - Ovatodiolide

KW - Cancer stem cell

KW - Chemoresistance

KW - JAK-STAT pathway

KW - Nasopharyngeal carcinoma

KW - Ovatodiolide

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U2 - 10.1016/j.phymed.2018.05.007

DO - 10.1016/j.phymed.2018.05.007

M3 - Article

VL - 56

SP - 269

EP - 278

JO - Phytomedicine

JF - Phytomedicine

SN - 0944-7113

ER -