Ginkgo biloba extract decreases non-small cell lung cancer cell migration by downregulating metastasis-associated factor heat-shock protein 27

Jong-Rung Tsai; Po-Len Liu; Yung-Hsiang Chen; Shah-Hwa Chou; Ming-Chan Yang; Yu-Jen Cheng; Jhi-Jhu Hwang; Wei-Hsian Yin; Inn-Wen Chong

doi:10.1371/journal.pone.0091331

Ginkgo biloba extract decreases non-small cell lung cancer cell migration by downregulating metastasis-associated factor heat-shock protein 27

PLoS One. 2014 Mar 11;9(3):e91331. doi: 10.1371/journal.pone.0091331. eCollection 2014.

Authors

Jong-Rung Tsai¹, Po-Len Liu², Yung-Hsiang Chen³, Shah-Hwa Chou⁴, Ming-Chan Yang⁵, Yu-Jen Cheng⁶, Jhi-Jhu Hwang¹, Wei-Hsian Yin⁷, Inn-Wen Chong¹

Affiliations

¹ Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
² Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
³ Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
⁴ Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Surgery, Division of Chest Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁵ Department of Surgery, Yuan's General Hospital, Kaohsiung, Taiwan.
⁶ Department of Health Management, Division of Thoracic Surgery, Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
⁷ Division of Cardiology, Cheng-Hsin General Hospital, Faculty of Medicine, and Cardiovascular Research Centre, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

Abstract

Heat-shock proteins (HSPs) are molecular chaperones that protect proteins from damage. HSP27 expression is associated with cancer transformation and invasion. Ginkgo biloba extract (EGb761), the most widely sold herbal supplement, has antiangiogenic effects and induces tumor apoptosis. Data regarding the effect of EGb761 on HSP expression is limited, particularly in cancer. HSP27 expression in paired tumors and normal lung tissues of 64 patients with non-small cell lung cancer (NSCLC) were detected by real-time PCR, western blotting, and immunohistochemistry. NSCLC cell lines (A549/H441) were used to examine the migratory abilities in vitro. NSCLC tissue showed higher HSP27 expression than normal lung tissue. Kaplan-Meier survival analysis showed that NSCLC patients with low HSP27 expression ratio (<1) had significantly longer survival time than those with a high expression ratio (>1) (p = 0.04). EGb761 inhibited HSP27 expression and migratory ability of A549/H441 cells, which is the same as HSP27-siRNA transfection effect. Moreover, EGb761 treatment activated the AKT and p38 pathways and did not affect the expression of PI3K, ERK, and JNK pathways. HSP27 is a poor prognostic indicator of NSCLC. EGb761 can decrease the migration ability of A549/H441 by inhibiting HSP27 expression most likely through AKT and p38 MAPK pathways activation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Antineoplastic Agents, Phytogenic / pharmacology*
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / metabolism
Carcinoma, Non-Small-Cell Lung / mortality
Carcinoma, Non-Small-Cell Lung / pathology
Cell Line, Tumor
Cell Movement / drug effects*
Cell Movement / genetics
Down-Regulation
Female
Gene Expression Regulation, Neoplastic / drug effects
Ginkgo biloba / chemistry*
HSP27 Heat-Shock Proteins / genetics*
HSP27 Heat-Shock Proteins / metabolism
Humans
Lung Neoplasms / genetics*
Lung Neoplasms / metabolism
Lung Neoplasms / mortality
Lung Neoplasms / pathology
Male
Middle Aged
Neoplasm Metastasis
Neoplasm Staging
Plant Extracts / pharmacology*
Proto-Oncogene Proteins c-akt / metabolism
RNA Interference
Signal Transduction / drug effects
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

Antineoplastic Agents, Phytogenic
HSP27 Heat-Shock Proteins
Plant Extracts
Ginkgo biloba extract
Proto-Oncogene Proteins c-akt
p38 Mitogen-Activated Protein Kinases

Grants and funding

This work was supported in part by grant KMU-Q098022 from the Kaohsiung Medical University, and grant NSC102-2314-B-037-067 from National Science Council, Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.