摘要
| 原文 | 英語 |
|---|---|
| 文章編號 | 33 |
| 期刊 | Chinese Medicine (United Kingdom) |
| 卷 | 12 |
| 發行號 | 1 |
| DOIs | |
| 出版狀態 | 已發佈 - 十一月 15 2017 |
指紋
ASJC Scopus subject areas
- Pharmacology
- Complementary and alternative medicine
引用此文
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. Chun; Lai, Gi Ming; Chow, Jyh Ming; Lee, Hsin Lun; Yeh, Chuan Feng; Li, Chi Han; Yan, Jiann Long; Chuang, Shuang En; Whang-Peng, Jacqueline; Bai, Kuan Jen; Yao, Chih Jung.
於: Chinese Medicine (United Kingdom), 卷 12, 編號 1, 33, 15.11.2017.研究成果: 雜誌貢獻 › 文章
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TY - JOUR
T1 - Active fraction (HS7) from Taiwanofungus camphoratus inhibits AKT-mTOR, ERK and STAT3 pathways and induces CDK inhibitors in CL1-0 human lung cancer cells
AU - Lai, I. Chun
AU - Lai, Gi Ming
AU - Chow, Jyh Ming
AU - Lee, Hsin Lun
AU - Yeh, Chuan Feng
AU - Li, Chi Han
AU - Yan, Jiann Long
AU - Chuang, Shuang En
AU - Whang-Peng, Jacqueline
AU - Bai, Kuan Jen
AU - Yao, Chih Jung
PY - 2017/11/15
Y1 - 2017/11/15
N2 - 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.
AB - 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.
KW - AKT-mTOR
KW - ERK
KW - HS7
KW - Non-small cell lung cancer
KW - STAT3
KW - Taiwanofungus camphoratus
UR - http://www.scopus.com/inward/record.url?scp=85034587259&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85034587259&partnerID=8YFLogxK
U2 - 10.1186/s13020-017-0154-9
DO - 10.1186/s13020-017-0154-9
M3 - Article
AN - SCOPUS:85034587259
VL - 12
JO - Chinese Medicine
JF - Chinese Medicine
SN - 1749-8546
IS - 1
M1 - 33
ER -