Ganoderma tsugaeInduces S Phase Arrest and Apoptosis in Doxorubicin-Resistant Lung Adenocarcinoma H23/0.3 Cells via Modulation of the PI3K/Akt Signaling Pathway

Author:

Yu Yang-Hao12,Kuo Han-Peng3,Hsieh Hui-Hsia4,Li Jhy-Wei5,Hsu Wu-Huei2,Chen Shih-Jung6,Su Muh-Hwan7,Liu Shwu-Huey8,Cheng Yung-Chi9,Chen Chih-Yi10,Kao Ming-Ching311

Affiliation:

1. Graduate Institute of Clinical and Medical Science, School of Medicine, China Medical University, Taichung 40402, Taiwan

2. Division of Pulmonary and Critical Care, China Medical University Hospital, Taichung 40447, Taiwan

3. Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung 40402, Taiwan

4. Pharmacy Department, China Medical University Hospital, Taichung 40447, Taiwan

5. Department of Pathology, Da-Chien General Hospital, Miaoli 36052, Taiwan

6. Luo-Gui-Ying Fungi Agriculture Farm, Taoyuan 33043, Taiwan

7. Sinphar Group R&D Center, Yilan 26944, Taiwan

8. Division of Drug Development, PhytoCeutica, Inc., New Haven, CT 06511-1989, USA

9. Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520-8066, USA

10. Division of Chest Surgery, China Medical University Hospital, Taichung 40447, Taiwan

11. Department of Biochemistry, National Defense Medical Center, Taipei 11490, Taiwan

Abstract

Ganoderma tsugae(GT) is a traditional Chinese medicine that exhibits significant antitumor activities against many types of cancer. This study investigated the molecular mechanism by which GT suppresses the growth of doxorubicin-resistant lung adenocarcinoma H23/0.3 cells. Our results reveal that GT inhibits the viability of H23/0.3 cellsin vitroandin vivoand sensitizes the growth suppression effect of doxorubicin on H23/0.3 cells. The data also show that GT induces S phase arrest by interfering with the protein expression of cyclin A, cyclin E, CDK2, and CDC25A. Furthermore, GT induces cellular apoptosis via induction of a mitochondria/caspase pathway. In addition, we also demonstrate that the suppression of cell proliferation by GT is through down-regulation of the PI3K/Akt signaling pathway. In conclusion, this study suggests that GT may be a useful adjuvant therapeutic agent in the treatment of lung cancer.

Funder

National Science Council

Publisher

Hindawi Limited

Subject

Complementary and alternative medicine

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