The licorice dietary component isoliquiritigenin chemosensitizes human uterine sarcoma cells to doxorubicin and inhibits cell growth by inducing apoptosis and autophagy via inhibition of m-TOR signaling

Li Chun Lin, Chi Hao Wu, Tzong Ming Shieh, Hsin Yuan Chen, Tsui Chin Huang, Shih Min Hsia

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Abstract

Uterine sarcoma is a rare gynecologic cancer. Doxorubicin (Dox) is widely used for treating several cancers, including uterine sarcoma. However, multidrug resistance is a major clinical problem and a critical cause of treatment failure. Strategies for increasing chemosensitivity and reducing the dose of chemotherapeutic agents should be established to prevent drug side effects, and the development of new chemotherapeutic agents is crucial. Isoliquiritigenin (ISL) is a natural flavonoid with a chalcone structure isolated from licorice root. ISL exhibits significant anticancer activities against many cancer types. In this study, we investigated the antitumor effects of ISL on the human uterine sarcoma cancer cell line MES-SA and the multidrug-resistant human uterine sarcoma cancer cell lines MES-SA/Dx5 and MES-SA/Dx5-R. Our results showed that treatment with ISL alone or in combination with Dox significantly inhibited the growth of cancer cells and increased the proportion of cells in the sub-G1 phase. Flow cytometry revealed that ISL induced apoptosis and necrosis. In addition, ISL enhanced the expression of autophagy-associated protein light chain 3 beta-II and apoptosis-associated protein cleaved poly(ADP-ribose) polymerase. ISL also inhibited protein expression of Bcl-2 and phosphorylated mechanistic target of rapamycin. Moreover, taken together, the results indicate that licorice dietary component ISL can inhibit human uterine sarcoma cancer cells by inducing apoptosis and autophagy and can increase the chemosensitivity of the multidrug-resistant human uterine sarcoma cancer cells MES-SA/Dx5 and MES-SA//Dx5-R to doxorubicin. Therefore, ISL-containing food might be beneficial for enhance cancer chemotherapy.

Original languageEnglish
Pages (from-to)332-344
Number of pages13
JournalJournal of Functional Foods
Volume33
DOIs
Publication statusPublished - Jun 1 2017

Fingerprint

Glycyrrhiza
licorice
doxorubicin
autophagy
Autophagy
sarcoma
Sarcoma
Doxorubicin
cell growth
apoptosis
Apoptosis
Uterine Neoplasms
Growth
cells
neoplasms
uterine neoplasms
cell lines
chalcone
NAD ADP-ribosyltransferase
multiple drug resistance

Keywords

  • Autophagy
  • Chemosensitizes
  • Doxorubicin
  • Human uterine sarcoma cells
  • Isoliquiritigenin
  • Licorice

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science
  • Nutrition and Dietetics

Cite this

@article{13c4e04346ed4427b3da8957659cc9a6,
title = "The licorice dietary component isoliquiritigenin chemosensitizes human uterine sarcoma cells to doxorubicin and inhibits cell growth by inducing apoptosis and autophagy via inhibition of m-TOR signaling",
abstract = "Uterine sarcoma is a rare gynecologic cancer. Doxorubicin (Dox) is widely used for treating several cancers, including uterine sarcoma. However, multidrug resistance is a major clinical problem and a critical cause of treatment failure. Strategies for increasing chemosensitivity and reducing the dose of chemotherapeutic agents should be established to prevent drug side effects, and the development of new chemotherapeutic agents is crucial. Isoliquiritigenin (ISL) is a natural flavonoid with a chalcone structure isolated from licorice root. ISL exhibits significant anticancer activities against many cancer types. In this study, we investigated the antitumor effects of ISL on the human uterine sarcoma cancer cell line MES-SA and the multidrug-resistant human uterine sarcoma cancer cell lines MES-SA/Dx5 and MES-SA/Dx5-R. Our results showed that treatment with ISL alone or in combination with Dox significantly inhibited the growth of cancer cells and increased the proportion of cells in the sub-G1 phase. Flow cytometry revealed that ISL induced apoptosis and necrosis. In addition, ISL enhanced the expression of autophagy-associated protein light chain 3 beta-II and apoptosis-associated protein cleaved poly(ADP-ribose) polymerase. ISL also inhibited protein expression of Bcl-2 and phosphorylated mechanistic target of rapamycin. Moreover, taken together, the results indicate that licorice dietary component ISL can inhibit human uterine sarcoma cancer cells by inducing apoptosis and autophagy and can increase the chemosensitivity of the multidrug-resistant human uterine sarcoma cancer cells MES-SA/Dx5 and MES-SA//Dx5-R to doxorubicin. Therefore, ISL-containing food might be beneficial for enhance cancer chemotherapy.",
keywords = "Autophagy, Chemosensitizes, Doxorubicin, Human uterine sarcoma cells, Isoliquiritigenin, Licorice",
author = "Lin, {Li Chun} and Wu, {Chi Hao} and Shieh, {Tzong Ming} and Chen, {Hsin Yuan} and Huang, {Tsui Chin} and Hsia, {Shih Min}",
year = "2017",
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TY - JOUR

T1 - The licorice dietary component isoliquiritigenin chemosensitizes human uterine sarcoma cells to doxorubicin and inhibits cell growth by inducing apoptosis and autophagy via inhibition of m-TOR signaling

AU - Lin, Li Chun

AU - Wu, Chi Hao

AU - Shieh, Tzong Ming

AU - Chen, Hsin Yuan

AU - Huang, Tsui Chin

AU - Hsia, Shih Min

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Uterine sarcoma is a rare gynecologic cancer. Doxorubicin (Dox) is widely used for treating several cancers, including uterine sarcoma. However, multidrug resistance is a major clinical problem and a critical cause of treatment failure. Strategies for increasing chemosensitivity and reducing the dose of chemotherapeutic agents should be established to prevent drug side effects, and the development of new chemotherapeutic agents is crucial. Isoliquiritigenin (ISL) is a natural flavonoid with a chalcone structure isolated from licorice root. ISL exhibits significant anticancer activities against many cancer types. In this study, we investigated the antitumor effects of ISL on the human uterine sarcoma cancer cell line MES-SA and the multidrug-resistant human uterine sarcoma cancer cell lines MES-SA/Dx5 and MES-SA/Dx5-R. Our results showed that treatment with ISL alone or in combination with Dox significantly inhibited the growth of cancer cells and increased the proportion of cells in the sub-G1 phase. Flow cytometry revealed that ISL induced apoptosis and necrosis. In addition, ISL enhanced the expression of autophagy-associated protein light chain 3 beta-II and apoptosis-associated protein cleaved poly(ADP-ribose) polymerase. ISL also inhibited protein expression of Bcl-2 and phosphorylated mechanistic target of rapamycin. Moreover, taken together, the results indicate that licorice dietary component ISL can inhibit human uterine sarcoma cancer cells by inducing apoptosis and autophagy and can increase the chemosensitivity of the multidrug-resistant human uterine sarcoma cancer cells MES-SA/Dx5 and MES-SA//Dx5-R to doxorubicin. Therefore, ISL-containing food might be beneficial for enhance cancer chemotherapy.

AB - Uterine sarcoma is a rare gynecologic cancer. Doxorubicin (Dox) is widely used for treating several cancers, including uterine sarcoma. However, multidrug resistance is a major clinical problem and a critical cause of treatment failure. Strategies for increasing chemosensitivity and reducing the dose of chemotherapeutic agents should be established to prevent drug side effects, and the development of new chemotherapeutic agents is crucial. Isoliquiritigenin (ISL) is a natural flavonoid with a chalcone structure isolated from licorice root. ISL exhibits significant anticancer activities against many cancer types. In this study, we investigated the antitumor effects of ISL on the human uterine sarcoma cancer cell line MES-SA and the multidrug-resistant human uterine sarcoma cancer cell lines MES-SA/Dx5 and MES-SA/Dx5-R. Our results showed that treatment with ISL alone or in combination with Dox significantly inhibited the growth of cancer cells and increased the proportion of cells in the sub-G1 phase. Flow cytometry revealed that ISL induced apoptosis and necrosis. In addition, ISL enhanced the expression of autophagy-associated protein light chain 3 beta-II and apoptosis-associated protein cleaved poly(ADP-ribose) polymerase. ISL also inhibited protein expression of Bcl-2 and phosphorylated mechanistic target of rapamycin. Moreover, taken together, the results indicate that licorice dietary component ISL can inhibit human uterine sarcoma cancer cells by inducing apoptosis and autophagy and can increase the chemosensitivity of the multidrug-resistant human uterine sarcoma cancer cells MES-SA/Dx5 and MES-SA//Dx5-R to doxorubicin. Therefore, ISL-containing food might be beneficial for enhance cancer chemotherapy.

KW - Autophagy

KW - Chemosensitizes

KW - Doxorubicin

KW - Human uterine sarcoma cells

KW - Isoliquiritigenin

KW - Licorice

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