Abstract
Background: The non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. In NSCLC, the oncogenic AKT-mTOR, ERK and STAT3 pathways are commonly dysregulated and have emerged as attractive targets for therapeutic developments. In a relatively limited subset of NSCLC, these pathways driven by mutant EGFR can be treated by the tyrosine kinase inhibitors (TKIs)-mediated targeted therapy. However, for the most NSCLC, more novel targeted agents are imperatively needed. Therefore, we investigated the inhibitory effects of the active fraction HS7 from Taiwanofungus camphoratus, a unique medicinal fungus in Taiwan, on these pathways in CL1-0 EGFR wild-type human NSCLC cells. Methods: The active fraction HS7 was prepared by n-hexane extraction of T. camphoratus followed by silica gel chromatography. Its effects on the cell viabilities were determined by sulforhodamine B colorimetric assay. Flow cytometry was used to analyze cell-cycle regulation and apoptosis induction. The changes in cellular protein levels were examined by Western blot. Results: The active fraction HS7 vigorously inhibits AKT-mTOR, ERK and STAT3 signaling pathways in CL1-0 cells. At dose of 25μg/mL, these signaling pathways were almost completely inhibited by HS7, accompanied with induction of cyclin-dependent kinase inhibitors such as p15, p21 and p27. Accordingly, the AKT-mTOR downstream targets p-p70S6K and HIF-1α were also suppressed as well. At this dose, the cell proliferation was profoundly suppressed to 23.4% of control and apoptosis induction was observed. Conclusions: The active fraction HS7 from n-hexane extract of T. camphoratus exerts multi-targeting activity on the suppression of AKT-mTOR, ERK and STAT3 pathways and induction of p15, p21 and p27 in EGFR wild-type NSCLC cells. This multi-targeting activity of HS7 suggests its potential as an alternative medicine for the treatment of EGFR TKIs resistant NSCLC.
Original language | English |
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Article number | 33 |
Journal | Chinese Medicine (United Kingdom) |
Volume | 12 |
Issue number | 1 |
DOIs | |
Publication status | Published - Nov 15 2017 |
Keywords
- AKT-mTOR
- ERK
- HS7
- Non-small cell lung cancer
- STAT3
- Taiwanofungus camphoratus
ASJC Scopus subject areas
- Pharmacology
- Complementary and alternative medicine
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MOESM3 of Active fraction (HS7) from Taiwanofungus camphoratus inhibits AKT-mTOR, ERK and STAT3 pathways and induces CDK inhibitors in CL1-0 human lung cancer cells
Whang-Peng, J. (Creator), Chow, J. (Contributor), Yan, J. (Contributor), Lee, H. (Contributor), Yeh, C. (Creator), Lai, I. (Contributor), Yao, C. (Contributor), Lai, G. (Contributor), Bai, K. (Contributor), Chuang, S. (Contributor) & Li, C. (Contributor), Figshare, 2017
DOI: 10.6084/m9.figshare.c.3931717_d3.v1, https://doi.org/10.6084%2Fm9.figshare.c.3931717_d3.v1
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Active fraction (HS7) from Taiwanofungus camphoratus inhibits AKT-mTOR, ERK and STAT3 pathways and induces CDK inhibitors in CL1-0 human lung cancer cells
Lai, I. (Contributor), Lai, G. (Contributor), Chow, J. (Contributor), Lee, H. (Contributor), Yeh, C. (Creator), Li, C. (Contributor), Yan, J. (Contributor), Chuang, S. (Contributor), Whang-Peng, J. (Creator), Bai, K. (Contributor) & Yao, C. (Contributor), Figshare, 2017
DOI: 10.6084/m9.figshare.c.3931717.v1, https://doi.org/10.6084%2Fm9.figshare.c.3931717.v1
Dataset
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MOESM1 of Active fraction (HS7) from Taiwanofungus camphoratus inhibits AKT-mTOR, ERK and STAT3 pathways and induces CDK inhibitors in CL1-0 human lung cancer cells
Lai, G. (Contributor), Li, C. (Contributor), Yeh, C. (Creator), Whang-Peng, J. (Creator), Lee, H. (Contributor), Yao, C. (Contributor), Lai, I. (Contributor), Chuang, S. (Contributor), Chow, J. (Contributor), Bai, K. (Contributor) & Yan, J. (Contributor), Figshare, 2017
DOI: 10.6084/m9.figshare.c.3931717_d1.v1, https://doi.org/10.6084%2Fm9.figshare.c.3931717_d1.v1
Dataset