Dataset Information

Andrographolide inhibits non-small cell lung cancer cell proliferation through the activation of the mitochondrial apoptosis pathway and by reprogramming host glucose metabolism.

ABSTRACT:

Background

The main aim of this research was to explore the role and mechanism of Andrographolide (Andro) in controlling non-small cell lung cancer (NSCLC) cell proliferation.

Methods

Human NSCLC H1975 cells were treated with Andro (0-20 µM) for 4-72 h. B-cell leukemia/lymphoma 2 (Bcl-2)-antagonist/killer (Bak)-small interfering RNA (siRNA) (Bak-siRNA) and fructose-1,6-bisphosphatase (FBP1)-siRNA were transfected into H1975 cells to inhibit the endogenic Bak and FBP1 expression, respectively, and their expressions were detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB). Cellular proliferation ability was determined through various assessments, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and cell counting kit-8 (CCK-8) assays. Cell apoptosis ability was measured using flow cytometry. Pro-apoptotic-related proteins (cleaved caspase 9, cleaved caspase 8, and cleaved caspase 3) and mitochondrial apoptosis pathway proteins [Bcl2-associated X (Bax), Bak, Bcl-2, and cytochrome C (cyto C)] were assessed by WB. Aerobic glycolysis-associated genes [pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), and glucose transporter 1 (GLUT1)] and gluconeogenesis genes [phosphoenolpyruvate carboxykinase 1 (PEPCK1), fructose-1,6-bisphosphatase 1 (FBP1), and phosphofructokinase (PFK)] were measured by qRT-PCR. The mitochondrial membrane depolarization sensor, 5, 50, 6, 60-tetrachloro-1, 10, 3, 30 tetraethyl benzimidazolo carbocyanine iodide (JC-1) assay was used for the measurement of mitochondrial membrane potential (ΔΨm). Additionally, glycolytic metabolism, lactate production, and adenosine triphosphate (ATP) synthesis were also analyzed.

Results

Andro inhibited human NSCLC cellular proliferation and induced apoptosis in a dose-time or dose-dependent manner via activation of the mitochondrial apoptosis pathway. Andro inhibited glycolysis, promoted the gluconeogenesis pathway, and increased the levels of cleaved caspase 9, cleaved caspase 8, cleaved caspase 3, Bax, Bak, PEPCK1, FBP1, and PFK, and decreased the levels of Bcl-2, PKM2, LDHA, and GLUT1. Moreover, it also decreased the ΔΨm and facilitated the release of cyto C from mitochondria into the cytoplasm. Furthermore, Andro enhanced the mitochondrial translocation of Bak, glucose uptake, lactate release, and intracellular ATP synthesis. Suppression of endogenic Bak and FBP1 expression significantly reduced the effects of Andro in H1975 cells.

Conclusions

Andro represses NSCLC cell proliferation through the activation of the mitochondrial apoptosis pathway and by reprogramming glucose metabolism.

SUBMITTER: Chen Z

PROVIDER: S-EPMC8667159 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Andrographolide inhibits non-small cell lung cancer cell proliferation through the activation of the mitochondrial apoptosis pathway and by reprogramming host glucose metabolism.

Chen Zhao Z Tang Wei-Jian WJ Zhou Yu-Han YH Chen Zhou-Miao ZM Liu Kai K

Annals of translational medicine 20211101 22

<h4>Background</h4>The main aim of this research was to explore the role and mechanism of Andrographolide (Andro) in controlling non-small cell lung cancer (NSCLC) cell proliferation.<h4>Methods</h4>Human NSCLC H1975 cells were treated with Andro (0-20 µM) for 4-72 h. B-cell leukemia/lymphoma 2 (Bcl-2)-antagonist/killer (Bak)-small interfering RNA (siRNA) (<i>Bak</i>-siRNA) and fructose-1,6-bisphosphatase (FBP1)-siRNA were transfected into H1975 cells to inhibit the endogenic Bak and FBP1 expres ...[more]

PMID: 34988210

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Dataset Information

Andrographolide inhibits non-small cell lung cancer cell proliferation through the activation of the mitochondrial apoptosis pathway and by reprogramming host glucose metabolism.

Background

Methods

Results

Conclusions

Publications

Andrographolide inhibits non-small cell lung cancer cell proliferation through the activation of the mitochondrial apoptosis pathway and by reprogramming host glucose metabolism.

Similar Datasets

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