Hexane fraction of adlay (Coix lachryma-jobi L.) testa ethanolic extract inhibits human uterine sarcoma cancer cells growth and chemosensitizes human uterine sarcoma cells to doxorubicin

Chih Chao Chang, Ling Hui Huang, Wenchang Chiang, Shih Min Hsia

研究成果: 雜誌貢獻文章

2 引文 (Scopus)

摘要

Background: Cancer has remained among the top ten causes of death in Taiwan since 1982. Uterine sarcoma is a rare gynecologic cancer, and chemotherapy is one type of cancer treatment. Doxorubicin (Dox) is widely used for treating several cancers, including uterine sarcoma, however, multidrug resistance (MDR) is a major clinical problem and a critical cause of treatment failure. The ethanolic extracts of adlay testa (ATE) exhibited significant anticancer activities against many cancer types. Purpose: In this study we investigated the antitumor effects of the hexane fraction of the adlay testa ethanolic extracts (ATE-Hex) on the human uterine sarcoma cancer cell line MES-SA, as well as on the multidrug-resistant human uterine sarcoma cancer cell line MES-SA/Dx5. Methods: The MTT assay was performed to assess the effects of the extracts of different parts of the adlay on the proliferation of human uterine sarcoma cells (MES-SA and MES-SA/Dx5) and human uterine smooth muscle cells (HUtSMCs). To determine whether ATE-Hex has a chemosensitizing effect on drug-resistant uterine sarcoma cells, the MTT assay was performed to examine the synergistic effects of ATE-Hex, the chemotherapeutic drug Dox alone, and in combination. Rhodamine accumulation was analyzed using fluorescence detection. Apoptotic cells were analyzed via flow cytometry. In addition, employing a flame ionization detector (GC/FID) gas chromatography was also developed as the analysis platform for ATE-Hex. Results: The results demonstrated that ATE-Hex exhibited the best effects of inhibition on MES-SA and MES-SA/Dx5 cells. Co-treatment of ATE-Hex and Dox could synergistically inhibit the proliferation of cancer cells. ATE-Hex reduced the rhodamine efflux in MES-SA/Dx5 cells, indicating that ATE-Hex could reduce the expression of P-gp. In addition, our results showed that treatment with ATE-Hex alone or in combination with Dox significantly inhibited the growth of cancer cells and induced apoptosis by increasing the sub-G1 phase and poly(ADP-ribose) polymerase (PARP) being cleaved. Flow cytometry revealed that ATE-Hex induced apoptosis. Conclusion: These results suggest that ATE-Hex can inhibit human uterine sarcoma cancer cells by inducing apoptosis and increasing the chemosensitivity of the multidrug-resistant human uterine sarcoma cancer cell MES-SA/Dx5 to Dox. Furthermore, the combination of ATE-Hex and Dox could decrease MDR and increase the synergistic effect.
原文英語
頁(從 - 到)69-80
頁數12
期刊Phytomedicine
47
DOIs
出版狀態已發佈 - 八月 1 2018

指紋

Coix
Uterine Neoplasms
Hexanes
Sarcoma
Doxorubicin
Growth
Neoplasms
Rhodamines
Multiple Drug Resistance
Apoptosis
Flow Cytometry
Flame Ionization
Cell Line
Poly(ADP-ribose) Polymerases
Myometrium
G1 Phase
Treatment Failure
Taiwan
Pharmaceutical Preparations
Gas Chromatography

ASJC Scopus subject areas

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

引用此文

@article{071263dc3e804fdaa390c3996e1ae2e2,
title = "Hexane fraction of adlay (Coix lachryma-jobi L.) testa ethanolic extract inhibits human uterine sarcoma cancer cells growth and chemosensitizes human uterine sarcoma cells to doxorubicin",
abstract = "Background: Cancer has remained among the top ten causes of death in Taiwan since 1982. Uterine sarcoma is a rare gynecologic cancer, and chemotherapy is one type of cancer treatment. Doxorubicin (Dox) is widely used for treating several cancers, including uterine sarcoma, however, multidrug resistance (MDR) is a major clinical problem and a critical cause of treatment failure. The ethanolic extracts of adlay testa (ATE) exhibited significant anticancer activities against many cancer types. Purpose: In this study we investigated the antitumor effects of the hexane fraction of the adlay testa ethanolic extracts (ATE-Hex) on the human uterine sarcoma cancer cell line MES-SA, as well as on the multidrug-resistant human uterine sarcoma cancer cell line MES-SA/Dx5. Methods: The MTT assay was performed to assess the effects of the extracts of different parts of the adlay on the proliferation of human uterine sarcoma cells (MES-SA and MES-SA/Dx5) and human uterine smooth muscle cells (HUtSMCs). To determine whether ATE-Hex has a chemosensitizing effect on drug-resistant uterine sarcoma cells, the MTT assay was performed to examine the synergistic effects of ATE-Hex, the chemotherapeutic drug Dox alone, and in combination. Rhodamine accumulation was analyzed using fluorescence detection. Apoptotic cells were analyzed via flow cytometry. In addition, employing a flame ionization detector (GC/FID) gas chromatography was also developed as the analysis platform for ATE-Hex. Results: The results demonstrated that ATE-Hex exhibited the best effects of inhibition on MES-SA and MES-SA/Dx5 cells. Co-treatment of ATE-Hex and Dox could synergistically inhibit the proliferation of cancer cells. ATE-Hex reduced the rhodamine efflux in MES-SA/Dx5 cells, indicating that ATE-Hex could reduce the expression of P-gp. In addition, our results showed that treatment with ATE-Hex alone or in combination with Dox significantly inhibited the growth of cancer cells and induced apoptosis by increasing the sub-G1 phase and poly(ADP-ribose) polymerase (PARP) being cleaved. Flow cytometry revealed that ATE-Hex induced apoptosis. Conclusion: These results suggest that ATE-Hex can inhibit human uterine sarcoma cancer cells by inducing apoptosis and increasing the chemosensitivity of the multidrug-resistant human uterine sarcoma cancer cell MES-SA/Dx5 to Dox. Furthermore, the combination of ATE-Hex and Dox could decrease MDR and increase the synergistic effect.",
keywords = "Adlay testa, Doxorubicin, HUtSMCs, MES-SA, MES-SA/Dx5, Multidrug resistance",
author = "Chang, {Chih Chao} and Huang, {Ling Hui} and Wenchang Chiang and Hsia, {Shih Min}",
year = "2018",
month = "8",
day = "1",
doi = "10.1016/j.phymed.2018.03.056",
language = "English",
volume = "47",
pages = "69--80",
journal = "Phytomedicine",
issn = "0944-7113",
publisher = "Urban und Fischer Verlag Jena",

}

TY - JOUR

T1 - Hexane fraction of adlay (Coix lachryma-jobi L.) testa ethanolic extract inhibits human uterine sarcoma cancer cells growth and chemosensitizes human uterine sarcoma cells to doxorubicin

AU - Chang, Chih Chao

AU - Huang, Ling Hui

AU - Chiang, Wenchang

AU - Hsia, Shih Min

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Background: Cancer has remained among the top ten causes of death in Taiwan since 1982. Uterine sarcoma is a rare gynecologic cancer, and chemotherapy is one type of cancer treatment. Doxorubicin (Dox) is widely used for treating several cancers, including uterine sarcoma, however, multidrug resistance (MDR) is a major clinical problem and a critical cause of treatment failure. The ethanolic extracts of adlay testa (ATE) exhibited significant anticancer activities against many cancer types. Purpose: In this study we investigated the antitumor effects of the hexane fraction of the adlay testa ethanolic extracts (ATE-Hex) on the human uterine sarcoma cancer cell line MES-SA, as well as on the multidrug-resistant human uterine sarcoma cancer cell line MES-SA/Dx5. Methods: The MTT assay was performed to assess the effects of the extracts of different parts of the adlay on the proliferation of human uterine sarcoma cells (MES-SA and MES-SA/Dx5) and human uterine smooth muscle cells (HUtSMCs). To determine whether ATE-Hex has a chemosensitizing effect on drug-resistant uterine sarcoma cells, the MTT assay was performed to examine the synergistic effects of ATE-Hex, the chemotherapeutic drug Dox alone, and in combination. Rhodamine accumulation was analyzed using fluorescence detection. Apoptotic cells were analyzed via flow cytometry. In addition, employing a flame ionization detector (GC/FID) gas chromatography was also developed as the analysis platform for ATE-Hex. Results: The results demonstrated that ATE-Hex exhibited the best effects of inhibition on MES-SA and MES-SA/Dx5 cells. Co-treatment of ATE-Hex and Dox could synergistically inhibit the proliferation of cancer cells. ATE-Hex reduced the rhodamine efflux in MES-SA/Dx5 cells, indicating that ATE-Hex could reduce the expression of P-gp. In addition, our results showed that treatment with ATE-Hex alone or in combination with Dox significantly inhibited the growth of cancer cells and induced apoptosis by increasing the sub-G1 phase and poly(ADP-ribose) polymerase (PARP) being cleaved. Flow cytometry revealed that ATE-Hex induced apoptosis. Conclusion: These results suggest that ATE-Hex can inhibit human uterine sarcoma cancer cells by inducing apoptosis and increasing the chemosensitivity of the multidrug-resistant human uterine sarcoma cancer cell MES-SA/Dx5 to Dox. Furthermore, the combination of ATE-Hex and Dox could decrease MDR and increase the synergistic effect.

AB - Background: Cancer has remained among the top ten causes of death in Taiwan since 1982. Uterine sarcoma is a rare gynecologic cancer, and chemotherapy is one type of cancer treatment. Doxorubicin (Dox) is widely used for treating several cancers, including uterine sarcoma, however, multidrug resistance (MDR) is a major clinical problem and a critical cause of treatment failure. The ethanolic extracts of adlay testa (ATE) exhibited significant anticancer activities against many cancer types. Purpose: In this study we investigated the antitumor effects of the hexane fraction of the adlay testa ethanolic extracts (ATE-Hex) on the human uterine sarcoma cancer cell line MES-SA, as well as on the multidrug-resistant human uterine sarcoma cancer cell line MES-SA/Dx5. Methods: The MTT assay was performed to assess the effects of the extracts of different parts of the adlay on the proliferation of human uterine sarcoma cells (MES-SA and MES-SA/Dx5) and human uterine smooth muscle cells (HUtSMCs). To determine whether ATE-Hex has a chemosensitizing effect on drug-resistant uterine sarcoma cells, the MTT assay was performed to examine the synergistic effects of ATE-Hex, the chemotherapeutic drug Dox alone, and in combination. Rhodamine accumulation was analyzed using fluorescence detection. Apoptotic cells were analyzed via flow cytometry. In addition, employing a flame ionization detector (GC/FID) gas chromatography was also developed as the analysis platform for ATE-Hex. Results: The results demonstrated that ATE-Hex exhibited the best effects of inhibition on MES-SA and MES-SA/Dx5 cells. Co-treatment of ATE-Hex and Dox could synergistically inhibit the proliferation of cancer cells. ATE-Hex reduced the rhodamine efflux in MES-SA/Dx5 cells, indicating that ATE-Hex could reduce the expression of P-gp. In addition, our results showed that treatment with ATE-Hex alone or in combination with Dox significantly inhibited the growth of cancer cells and induced apoptosis by increasing the sub-G1 phase and poly(ADP-ribose) polymerase (PARP) being cleaved. Flow cytometry revealed that ATE-Hex induced apoptosis. Conclusion: These results suggest that ATE-Hex can inhibit human uterine sarcoma cancer cells by inducing apoptosis and increasing the chemosensitivity of the multidrug-resistant human uterine sarcoma cancer cell MES-SA/Dx5 to Dox. Furthermore, the combination of ATE-Hex and Dox could decrease MDR and increase the synergistic effect.

KW - Adlay testa

KW - Doxorubicin

KW - HUtSMCs

KW - MES-SA

KW - MES-SA/Dx5

KW - Multidrug resistance

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U2 - 10.1016/j.phymed.2018.03.056

DO - 10.1016/j.phymed.2018.03.056

M3 - Article

VL - 47

SP - 69

EP - 80

JO - Phytomedicine

JF - Phytomedicine

SN - 0944-7113

ER -