Xanthorrhizol induces apoptosis through ROS-mediated MAPK activation in human oral squamous cell carcinoma cells and inhibits DMBA-induced oral carcinogenesis in hamsters

Ju Yeon Kim, Jeong Mi An, WonYoon Chung, Kwang Kyun Park, Jae-Kwan Hwang, Du Sik Kim, Su Ryeon Seo, Jeong Taeg Seo

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Xanthorrhizol, a natural sesquiterpenoid compound isolated from Curcuma xanthorrhiza Roxb, has been known to inhibit the growth of human colon, breast, liver and cervical cancer cells. In this study, xanthorrhizol decreased cell viability, induced apoptosis and decreased the level of full-length PARP in SCC-15 oral squamous cell carcinoma (OSCC) cells. A decrease in cell viability and PARP degradation was not prevented by treatment with the caspase inhibitor Z-VAD-fmk in xanthorrhizol-treated cells. Xanthorrhizol treatment elevated intracellular Ca2+ and ROS levels in SCC-15 cells. Treatment with a Ca2+ chelator, EGTA/AM, did not affect xanthorrhizol- induced cytotoxicity, but cell viability was partly recovered by treatment with endogenous antioxidant, GSH, or hydroxy radical trapper, MCI-186. Furthermore, the viability of xanthorrhizol-treated SCC-15 cells was significantly restored by treatment with SB203580 and/or SP600125 but not significantly by PD98059 treatment. Xanthorrhizol-induced activation of p38 MAPK and JNK was blocked by MCI-186. Finally, xanthorrhizol suppressed the number of tumors in buccal pouches and increased the survival rate in hamsters treated with 7,12-dimethylbenz[a]anthracene. In conclusion, xanthorrhizol may induce caspase-independent apoptosis through ROS-mediated p38 MAPK and JNK activation in SCC-15 OSCC cells and prevent chemical-induced oral carcinogenesis. Therefore, xanthorrhizol seems to be a promising chemopreventive agent.

Original languageEnglish
Pages (from-to)493-498
Number of pages6
JournalPhytotherapy Research
Volume27
Issue number4
DOIs
Publication statusPublished - 2013 Apr 1

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9,10-Dimethyl-1,2-benzanthracene
Cricetinae
Squamous Cell Carcinoma
Carcinogenesis
Apoptosis
Cell Survival
p38 Mitogen-Activated Protein Kinases
xanthorrhizol
Curcuma
Caspase Inhibitors
Cheek
Liver Neoplasms
Chelating Agents
Caspases
Uterine Cervical Neoplasms
Colonic Neoplasms
Antioxidants
Breast Neoplasms

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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title = "Xanthorrhizol induces apoptosis through ROS-mediated MAPK activation in human oral squamous cell carcinoma cells and inhibits DMBA-induced oral carcinogenesis in hamsters",
abstract = "Xanthorrhizol, a natural sesquiterpenoid compound isolated from Curcuma xanthorrhiza Roxb, has been known to inhibit the growth of human colon, breast, liver and cervical cancer cells. In this study, xanthorrhizol decreased cell viability, induced apoptosis and decreased the level of full-length PARP in SCC-15 oral squamous cell carcinoma (OSCC) cells. A decrease in cell viability and PARP degradation was not prevented by treatment with the caspase inhibitor Z-VAD-fmk in xanthorrhizol-treated cells. Xanthorrhizol treatment elevated intracellular Ca2+ and ROS levels in SCC-15 cells. Treatment with a Ca2+ chelator, EGTA/AM, did not affect xanthorrhizol- induced cytotoxicity, but cell viability was partly recovered by treatment with endogenous antioxidant, GSH, or hydroxy radical trapper, MCI-186. Furthermore, the viability of xanthorrhizol-treated SCC-15 cells was significantly restored by treatment with SB203580 and/or SP600125 but not significantly by PD98059 treatment. Xanthorrhizol-induced activation of p38 MAPK and JNK was blocked by MCI-186. Finally, xanthorrhizol suppressed the number of tumors in buccal pouches and increased the survival rate in hamsters treated with 7,12-dimethylbenz[a]anthracene. In conclusion, xanthorrhizol may induce caspase-independent apoptosis through ROS-mediated p38 MAPK and JNK activation in SCC-15 OSCC cells and prevent chemical-induced oral carcinogenesis. Therefore, xanthorrhizol seems to be a promising chemopreventive agent.",
author = "Kim, {Ju Yeon} and An, {Jeong Mi} and WonYoon Chung and Park, {Kwang Kyun} and Jae-Kwan Hwang and Kim, {Du Sik} and Seo, {Su Ryeon} and Seo, {Jeong Taeg}",
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Xanthorrhizol induces apoptosis through ROS-mediated MAPK activation in human oral squamous cell carcinoma cells and inhibits DMBA-induced oral carcinogenesis in hamsters. / Kim, Ju Yeon; An, Jeong Mi; Chung, WonYoon; Park, Kwang Kyun; Hwang, Jae-Kwan; Kim, Du Sik; Seo, Su Ryeon; Seo, Jeong Taeg.

In: Phytotherapy Research, Vol. 27, No. 4, 01.04.2013, p. 493-498.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Kim, Ju Yeon

AU - An, Jeong Mi

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AU - Hwang, Jae-Kwan

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AU - Seo, Su Ryeon

AU - Seo, Jeong Taeg

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AB - Xanthorrhizol, a natural sesquiterpenoid compound isolated from Curcuma xanthorrhiza Roxb, has been known to inhibit the growth of human colon, breast, liver and cervical cancer cells. In this study, xanthorrhizol decreased cell viability, induced apoptosis and decreased the level of full-length PARP in SCC-15 oral squamous cell carcinoma (OSCC) cells. A decrease in cell viability and PARP degradation was not prevented by treatment with the caspase inhibitor Z-VAD-fmk in xanthorrhizol-treated cells. Xanthorrhizol treatment elevated intracellular Ca2+ and ROS levels in SCC-15 cells. Treatment with a Ca2+ chelator, EGTA/AM, did not affect xanthorrhizol- induced cytotoxicity, but cell viability was partly recovered by treatment with endogenous antioxidant, GSH, or hydroxy radical trapper, MCI-186. Furthermore, the viability of xanthorrhizol-treated SCC-15 cells was significantly restored by treatment with SB203580 and/or SP600125 but not significantly by PD98059 treatment. Xanthorrhizol-induced activation of p38 MAPK and JNK was blocked by MCI-186. Finally, xanthorrhizol suppressed the number of tumors in buccal pouches and increased the survival rate in hamsters treated with 7,12-dimethylbenz[a]anthracene. In conclusion, xanthorrhizol may induce caspase-independent apoptosis through ROS-mediated p38 MAPK and JNK activation in SCC-15 OSCC cells and prevent chemical-induced oral carcinogenesis. Therefore, xanthorrhizol seems to be a promising chemopreventive agent.

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