4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

Ching Yu Yen, Chien Chih Chiu, Fang Rong Chang, Jeff Y. Chen, Chi Ching Hwang, You Cheng Hseu, Hsin Ling Yang, Alan Yueh Luen Lee, Ming Tz Tsai, Zong Lun Guo, Yu Shan Cheng, Yin Chang Liu, Yu Hsuan Lan, Yu Ching Chang, Ying Chin Ko, Hsueh Wei Chang, Yang Chang Wu

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Abstract

Background: The crude extract of the fruit bearing plant, Physalis peruviana (golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown.Methods: Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug.Results: It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (p <0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4βHWE in both dose- and time-dependent manners (p <0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC50) of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G1 accumulation and slight arrest at the G2/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G2/M arrest for H1299 cells treated with 5 μg/mL for 24 h.Conclusions: In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.

Original languageEnglish
Article number46
JournalBMC Cancer
Volume10
DOIs
Publication statusPublished - Feb 18 2010

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Physalis
DNA Damage
Fruit
Lung Neoplasms
Apoptosis
Growth
Cell Cycle
Trypan Blue
Propidium
G2 Phase
Annexin A5
Complex Mixtures
Cell Division
Inhibitory Concentration 50
Fluorescent Antibody Technique
Hepatocellular Carcinoma
Anti-Inflammatory Agents
Cell Proliferation
Staining and Labeling
Cell Line

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

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4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest. / Yen, Ching Yu; Chiu, Chien Chih; Chang, Fang Rong; Chen, Jeff Y.; Hwang, Chi Ching; Hseu, You Cheng; Yang, Hsin Ling; Lee, Alan Yueh Luen; Tsai, Ming Tz; Guo, Zong Lun; Cheng, Yu Shan; Liu, Yin Chang; Lan, Yu Hsuan; Chang, Yu Ching; Ko, Ying Chin; Chang, Hsueh Wei; Wu, Yang Chang.

In: BMC Cancer, Vol. 10, 46, 18.02.2010.

Research output: Contribution to journalArticle

Yen, CY, Chiu, CC, Chang, FR, Chen, JY, Hwang, CC, Hseu, YC, Yang, HL, Lee, AYL, Tsai, MT, Guo, ZL, Cheng, YS, Liu, YC, Lan, YH, Chang, YC, Ko, YC, Chang, HW & Wu, YC 2010, '4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest', BMC Cancer, vol. 10, 46. https://doi.org/10.1186/1471-2407-10-46
Yen, Ching Yu ; Chiu, Chien Chih ; Chang, Fang Rong ; Chen, Jeff Y. ; Hwang, Chi Ching ; Hseu, You Cheng ; Yang, Hsin Ling ; Lee, Alan Yueh Luen ; Tsai, Ming Tz ; Guo, Zong Lun ; Cheng, Yu Shan ; Liu, Yin Chang ; Lan, Yu Hsuan ; Chang, Yu Ching ; Ko, Ying Chin ; Chang, Hsueh Wei ; Wu, Yang Chang. / 4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest. In: BMC Cancer. 2010 ; Vol. 10.
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abstract = "Background: The crude extract of the fruit bearing plant, Physalis peruviana (golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown.Methods: Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug.Results: It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (p <0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4βHWE in both dose- and time-dependent manners (p <0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC50) of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G1 accumulation and slight arrest at the G2/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G2/M arrest for H1299 cells treated with 5 μg/mL for 24 h.Conclusions: In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.",
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T1 - 4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

AU - Yen, Ching Yu

AU - Chiu, Chien Chih

AU - Chang, Fang Rong

AU - Chen, Jeff Y.

AU - Hwang, Chi Ching

AU - Hseu, You Cheng

AU - Yang, Hsin Ling

AU - Lee, Alan Yueh Luen

AU - Tsai, Ming Tz

AU - Guo, Zong Lun

AU - Cheng, Yu Shan

AU - Liu, Yin Chang

AU - Lan, Yu Hsuan

AU - Chang, Yu Ching

AU - Ko, Ying Chin

AU - Chang, Hsueh Wei

AU - Wu, Yang Chang

PY - 2010/2/18

Y1 - 2010/2/18

N2 - Background: The crude extract of the fruit bearing plant, Physalis peruviana (golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown.Methods: Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug.Results: It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (p <0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4βHWE in both dose- and time-dependent manners (p <0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC50) of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G1 accumulation and slight arrest at the G2/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G2/M arrest for H1299 cells treated with 5 μg/mL for 24 h.Conclusions: In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.

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