Active fraction (HS7) from Taiwanofungus camphoratus inhibits AKT-mTOR, ERK and STAT3 pathways and induces CDK inhibitors in CL1-0 human lung cancer cells

Abstract

BackgroundThe 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.MethodsThe 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.ResultsThe active fraction HS7 vigorously inhibits AKT-mTOR, ERK and STAT3 signaling pathways in CL1-0 cells. At dose of 25 μg/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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (10.1186/s13020-017-0154-9) contains supplementary material, which is available to authorized users.

Fungal Immunomodulatory Protein from Nectria haematococca Suppresses Growth of Human Lung Adenocarcinoma by Inhibiting the PI3K/Akt Pathway

“…Fungal products display widespread biological activities such as anti-inflammation, anti-cancer, and immunomodulatory effects, and thus these species represent a wealth of functional foods and drug precursors [ 8 , 9 ]. Mounting evidence suggests that fungal extracts might protect against certain types of cancers, especially lung adenocarcinoma [ 10 , 11 ]. Among them, fungal immunomodulatory proteins (FIPs), which are widely found in fungi, have well-known, strong inhibitory effects on lung adenocarcinoma.…”

Huanglian Jiedu Decoction ameliorates DSS-induced colitis in mice via the JAK2/STAT3 signalling pathway

“…In UC patients, the severity of the intestinal lesion was positively correlated with the expression of STAT3 [22]. To further elucidate the effect of HJD on JAK2/STAT3 pathway, AG490, a specific JAK2 inhibitor, was used to block the JAK2/STAT3 pathway [24]. We found that, similar to that reported about the overexpression of STAT3 and NF-KB caused abnormal activation of JAK2/STAT3 pathway [25], the expressions of JAK2 and STAT3 in the UC group were significantly increased.…”

Anti-cancer effects of Rhizoma Curcumae against doxorubicin-resistant breast cancer cells

“…Western blotting assay was performed according to previous studies [ 34 ]. Briefly, exponentially growing cells were seeded in culture dish (100 mm) at a density of 2 × 10 6 /dish and allowed to attach overnight.…”