Flavonoid-Rich Extract of <italic style="font-style: italic">Oldenlandia diffusa</italic> (Willd.) Roxb. Inhibits Gastric Cancer by Activation of Caspase-Dependent Mitochondrial Apoptosis

LING Jia-yin; WANG Qiu-lan; LIANG Hao-nan; LIU Qing-bo; YIN Dong-hong; LIN Li

doi:10.1007/s11655-022-3679-4

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Flavonoid-Rich Extract of Oldenlandia diffusa (Willd.) Roxb. Inhibits Gastric Cancer by Activation of Caspase-Dependent Mitochondrial Apoptosis

Original Article | Updated：2023-02-22

- Flavonoid-Rich Extract of Oldenlandia diffusa (Willd.) Roxb. Inhibits Gastric Cancer by Activation of Caspase-Dependent Mitochondrial Apoptosis
- Flavonoid-Rich Extract of Oldenlandia diffusa (Willd.) Roxb. Inhibits Gastric Cancer by Activation of Caspase-Dependent Mitochondrial Apoptosis
- 中国结合医学杂志（英文版） 2023年29卷第3期页码：213-223
- Affiliations：
  
  1.First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou (730000), China
  2.Gansu Provincial Hospital, Lanzhou (730000), China
  3.College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou (730000), China
  4.Institute of Chinese (Tibetan) Medicine Resources, Gansu University of Chinese Medicine, Lanzhou (730000), China
- Author bio：
  
  Associate Prof. WANG Qiu-lan, E-mail:qiulwang@163.com
- Funds：
  
  the Key Research and Development Program of Gansu Province(21YF5FA131);the Innovation Fund of Gansu Universities(2021A-084);the Graduate Innovation Fund of Gansu University of Chinese Medicine(2021CX49)
- DOI：10.1007/s11655-022-3679-4
  中图分类号：
- 纸质出版日期：2023-03，
  
  网络出版日期：2022-08-31，
  
  录用日期：2022-04-25
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Flavonoid-Rich Extract of Oldenlandia diffusa (Willd.) Roxb. Inhibits Gastric Cancer by Activation of Caspase-Dependent Mitochondrial Apoptosis[J]. 中国结合医学杂志（英文版）, 2023,29(3):213-223.

LING Jia-yin, WANG Qiu-lan, LIANG Hao-nan, et al. Flavonoid-Rich Extract of Oldenlandia diffusa (Willd.) Roxb. Inhibits Gastric Cancer by Activation of Caspase-Dependent Mitochondrial Apoptosis[J]. Chinese Journal of Integrative Medicine, 2023,29(3):213-223.
Flavonoid-Rich Extract of Oldenlandia diffusa (Willd.) Roxb. Inhibits Gastric Cancer by Activation of Caspase-Dependent Mitochondrial Apoptosis[J]. 中国结合医学杂志（英文版）, 2023,29(3):213-223. DOI： 10.1007/s11655-022-3679-4.

LING Jia-yin, WANG Qiu-lan, LIANG Hao-nan, et al. Flavonoid-Rich Extract of Oldenlandia diffusa (Willd.) Roxb. Inhibits Gastric Cancer by Activation of Caspase-Dependent Mitochondrial Apoptosis[J]. Chinese Journal of Integrative Medicine, 2023,29(3):213-223. DOI： 10.1007/s11655-022-3679-4.

摘要

Abstract

Objective:

To evaluate the apoptosis and cycle arrest effects of

Oldenlandia diffusa

flavonoids on human gastric cancer cells

determine the action mechanisms in association with the mitochondrial dependent signal transduction pathway that controls production of reactive oxygen species (ROS)

and evaluate the pharmacodynamics of a mouse xenotransplantation model to provide a reference for the use of flavonoids in prevention and treatment of gastric cancer.

Methods:

Flavonoids were extracted by an enzymatic-ultrasonic assisted method and purified with D-101 resin. Bioactive components were characterized by high-performance liquid chromatography. Cell lines MKN-45

AGS

and GES-1 were treated with different concentrations of flavonoids (64

128

and 160 μg/mL). The effect of flavonoids on cell viability was evaluated by MTT method

and cell nuclear morphology was observed by Hoechst staining. The apoptosis rate and cell cycle phases were measured by flow cytometry

the production of ROS was detected by laser confocal microscope

the mitochondrial membrane potential (MMP) were observed by fluorescence microscope

and the expression of apoptotic proteins related to activation of mitochondrial pathway were measured by immunoblotting. MKN-45 cells were transplanted into BALB/c nude mice to establish a xenograft tumor model. Hematoxylin and eosin staining was used to reveal the subcutaneous tumor tissue. The tumor volume and tumor weight were measured

the expression levels of proliferation markers proliferating cell nuclear antigen (PCNA) and Ki-67 were detected by immunohistochemistry

and the expression levels of CA72-4 were measured by enzyme linked immunosorbent assay.

Results:

Oldenlandia diffusa

flavonoids inhibited proliferation of MKN-45 and AGS human gastric cancer cells

arrested the cell cycle in G

/S phase

induced accumulation of ROS in the process of apoptosis

and altered MMP. In addition

flavonoids increased Apaf-1

Cleaved-Caspase-3

and Bax

and decreased Cyclin A

Cdk2

Bcl-2

Pro-Caspase-9

and Mitochondrial Cytochrome C (

0.05). The MKN-45 cell mouse xenotransplantation model further clarified the growth inhibitory effect of flavonoids towards tumors. The expression levels of PCNA and Ki-67 decreased in each flavonoid dose group

the expression level of CA72-4 decreased (

0.05).

Conclusion:

Flavonoids derived from

Oldenlandia diffusa

can inhibit proliferation and induce apoptosis of human gastric cancer cells by activating the mitochondrial controlled signal transduction pathway.

关键词

Keywords

Chinese medicineOldenlandia diffusa flavonoidsgastric cancerapoptosismitochondria

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Flavonoid-Rich Extract of Oldenlandia diffusa (Willd.) Roxb. Inhibits Gastric Cancer by Activation of Caspase-Dependent Mitochondrial Apoptosis

Flavonoid-Rich Extract of Oldenlandia diffusa (Willd.) Roxb. Inhibits Gastric Cancer by Activation of Caspase-Dependent Mitochondrial Apoptosis

DOI：10.1007/s11655-022-3679-4

摘要

Abstract

关键词

Keywords

references