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Physalin A induces G2/M phase cell cycle arrest in human non-small cell lung cancer cells: involvement of the p38 MAPK/ROS pathway

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Abstract

Physalin A (PA) is an active withanolide isolated from Physalis alkekengi var. franchetii, a traditional Chinese herbal medicine named Jindenglong, which has long been used for the treatment of sore throat, hepatitis, and tumors in China. In the present study, we firstly investigated the effects of PA on proliferation and cell cycle distribution of the human non-small cell lung cancer (NSCLC) A549 cell line, and the potential mechanisms involved. Here, PA inhibited cell growth in dose- and time-dependent manners. Treatment of A549 cells with 28.4 μM PA for 24 h resulted in approximately 50 % cell death. PA increased the amount of intracellular ROS and the proportion of cells in G2/M. G2/M arrest was attenuated by the addition of ROS scavenger NAC. ERK and P38 were triggered by PA through phosphorylation in a time-dependent manner. The phosphorylation of ERK and P38 were not attenuated by the addition of NAC, but the use of the p38 inhibitor could reduce, at least in part, PA-induced ROS and the proportion of cells in G2/M. PA induces G2/M cell cycle arrest in A549 cells involving in the p38 MAPK/ROS pathway. This study suggests that PA might be a promising therapeutic agent against NSCLC.

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Abbreviations

ANOVA:

Analysis of variance

DCF-DA:

2′,7′-Dichloro -fluorescein diacetate

DMSO:

Dimethyl sulfoxide

FBS:

Fetal bovine serum

iNOS:

Inducible nitric oxide synthase

LSD:

Least significant difference

MAPKs:

Mitogen-activated protein kinases

MPF:

Mitosis-promoting factor

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NAC:

N-Acetylcysteine

NO:

Nitric oxide

NSCLC:

Non-small cell lung cancer

PA:

Physalin A

PI:

Propidium iodide

ROS:

Reactive oxygen species

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Acknowledgments

This work was supported by National Natural Science Foundation of China (No. 21472138), the China Postdoctoral Science Foundation (No. 2013M541192), and the China Postdoctoral Science Special Foundation (No. 2014T70224).

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Authors and Affiliations

  1. School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin, 300193, People’s Republic of China

    Ning Kang, Qiang Zhang, Yi-yuan Huang & Yan-fei Peng

  2. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin, 300193, People’s Republic of China

    Ning Kang & Xiu-mei Gao

  3. College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin, 300193, People’s Republic of China

    Feng Qiu

  4. Department of Natural Products Chemistry, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People’s Republic of China

    Shi-jie Cao

  5. Department of Biochemistry and Molecular Biology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People’s Republic of China

    Jun-feng Jian & Yi-wei Mao

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  1. Ning Kang
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Correspondence to Feng Qiu or Xiu-mei Gao.

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Kang, N., Jian, Jf., Cao, Sj. et al. Physalin A induces G2/M phase cell cycle arrest in human non-small cell lung cancer cells: involvement of the p38 MAPK/ROS pathway. Mol Cell Biochem 415, 145–155 (2016). https://doi.org/10.1007/s11010-016-2686-1

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