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Herbal formula YYJD inhibits tumor growth by inducing cell cycle arrest and senescence in lung cancer.

ABSTRACT: Lung cancer represents a major cause of cancer-related death worldwide. Although various tactics and anti-tumor drugs have been used to improve curative effects, five-year survival rate of lung cancer patients remains poor. In this study, we investigated the action and underlying mechanisms of our recently optimized Chinese herbal formula Yangyinjiedu (YYJD) against lung cancer. YYJD significantly inhibits the proliferation of lung cancer cell lines (95-D, A549, H460 and H1975) by inducing cell cycle arrest and senescence in a dose-dependent manner. In particular, YYJD induces significant G2/M phase arrest and inhibits the colony formation of lung cancer cells. Moreover, we found that administration of YYJD could inhibit the growth of xenografted lung cancer cells in nude mice without loss in body weight. Our findings suggest that the herbal formula YYJD is a potential anti-tumor agent against lung cancer.

SUBMITTER: Zheng T

PROVIDER: S-EPMC5504005 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Herbal formula YYJD inhibits tumor growth by inducing cell cycle arrest and senescence in lung cancer.

Zheng Tingting T Que Zujun Z Jiao Lijing L Kang Yani Y Gong Yabin Y Yao Jialin J Ma Chao C Bi Ling L Dong Qihan Q Zhao Xiaodong X Xu Ling L

Scientific reports 20170710 1

Lung cancer represents a major cause of cancer-related death worldwide. Although various tactics and anti-tumor drugs have been used to improve curative effects, five-year survival rate of lung cancer patients remains poor. In this study, we investigated the action and underlying mechanisms of our recently optimized Chinese herbal formula Yangyinjiedu (YYJD) against lung cancer. YYJD significantly inhibits the proliferation of lung cancer cell lines (95-D, A549, H460 and H1975) by inducing cell ...[more]

PMID: 28694520

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Project description:BackgroundWe have previously demonstrated the epidermal growth factor receptor (EGFR)-targeted hybrid plasmonic magnetic nanoparticles (225-NP) produce a therapeutic effect in human lung cancer cell lines in vitro. In the present study, we investigated the molecular mechanism of 225-NP-mediated antitumor activity both in vitro and in vivo using the EGFR-mutant HCC827 cell line.MethodsThe growth inhibitory effect of 225-NP on lung tumor cells was determined by cell viability and cell-cycle analysis. Protein expression related to autophagy, apoptosis, and DNA-damage were determined by Western blotting and immunofluorescence. An in vivo efficacy study was conducted using a human lung tumor xenograft mouse model.ResultsThe 225-NP treatment markedly reduced tumor cell viability at 72 hours compared with the cell viability in control treatment groups. Cell-cycle analysis showed the percentage of cells in the G2/M phase was reduced when treated with 225-NP, with a concomitant increase in the number of cells in Sub-G1 phase, indicative of cell death. Western blotting showed LC3B and PARP cleavage, indicating 225-NP-treatment activated both autophagy- and apoptosis-mediated cell death. The 225-NP strongly induced γH2AX and phosphorylated histone H3, markers indicative of DNA damage and mitosis, respectively. Additionally, significant γH2AX foci formation was observed in 225-NP-treated cells compared with control treatment groups, suggesting 225-NP induced cell death by triggering DNA damage. The 225-NP-mediated DNA damage involved abrogation of the G2/M checkpoint by inhibiting BRCA1, Chk1, and phospho-Cdc2/CDK1 protein expression. In vivo therapy studies showed 225-NP treatment reduced EGFR phosphorylation, increased γH2AX foci, and induced tumor cell apoptosis, resulting in suppression of tumor growth.ConclusionThe 225-NP treatment induces DNA damage and abrogates G2/M phase of the cell cycle, leading to cellular apoptosis and suppression of lung tumor growth both in vitro and in vivo. Our findings provide a rationale for combining 225-NP with other DNA-damaging agents for achieving enhanced anticancer activity.

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Herbal formula YYJD inhibits tumor growth by inducing cell cycle arrest and senescence in lung cancer.

Publications

Herbal formula YYJD inhibits tumor growth by inducing cell cycle arrest and senescence in lung cancer.

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