Gigantol

BMC Complement Altern Med. 2018 Feb 14;18(1):59.

Gigantol inhibits Wnt/β-catenin signaling and exhibits anticancer activity in breast cancer cells.[Pubmed: 29444668 ]

Gigantol is a bibenzyl compound derived from several medicinal orchids. This biologically active compound has been shown to have promising therapeutic potential against cancer cells, but its mechanism of action remains unclear.
METHODS AND RESULTS:
The inhibitory effect of Gigantol on Wnt/β-catenin signaling was evaluated with the SuperTOPFlash reporter system. The levels of phosphorylated low-density lipoprotein receptor related protein 6 (LRP6), total LRP6 and cytosolic β-catenin were determined by Western blot analysis. The expression of Wnt target genes was analyzed using real-time PCR. Cell viability was measured with a MTT assay. The effect of Gigantol on cell migration was examined using scratch wound-healing and transwell migration assays. Gigantol decreased the level of phosphorylated LRP6 and cytosolic β-catenin in HEK293 cells. In breast cancer MDA-MB-231 and MDA-MB-468 cells, treatment with Gigantol reduced the level of phosphorylated LRP6, total LRP6 and cytosolic β-catenin in a dose-dependent manner, resulting in a decrease in the expression of Wnt target genes Axin2 and Survivin. We further demonstrated that Gigantol suppressed the viability and migratory capacity of breast cancer cells.
CONCLUSIONS:
Gigantol is a novel inhibitor of the Wnt/β-catenin pathway. It inhibits Wnt/β-catenin signaling through downregulation of phosphorylated LRP6 and cytosolic β-catenin in breast cancer cells.

J Ethnopharmacol. 2017 Feb 23;198:255-261.

Gigantol from Dendrobium chrysotoxum Lindl. binds and inhibits aldose reductase gene to exert its anti-cataract activity: An in vitro mechanistic study.[Pubmed: 28104409]

Dendrobium. chrysotoxum Lindl is a commonly used species of medicinal Dendrobium which belongs to the family of Orchidaceae, locally known as "Shihu" or "Huangcao". D. chrysotoxum Lindl is widely known for medicinal values in traditional Chinese medicine as it possesses anti-inflammatory, anti-hyperglycemic induction, antitumor and antioxidant properties. To characterize the interaction between Gigantol extracted from D. chrysotoxum Lindl and the AR gene, and determine Gigantol's efficacy against cataractogenesis.
METHODS AND RESULTS:
Human lens epithelial cells (HLECs) were induced by glucose as the model group. Reverse transcription polymerase chain reaction (RT-PCR) was used to assess AR gene expression. Then, the mode of interaction of Gigantol with the AR gene was evaluated by UV-visible spectroscopy, atomic force microscope (AFM) and surface-enhanced Raman spectroscopy (SERS). The binding constant was determined by UV-visible. Gigantol depressed AR gene expression in HLECs. UV-visible spectra preliminarily indicated that interaction between the AR gene and Gigantol may follow the groove mode, with a binding constant of 1.85×103L/mol. Atomic force microscope (AFM) data indicated that Gigantol possibly bound to insert AR gene base pairs of the double helix. Surface-enhanced Raman spectroscopy (SERS) studies further supported these observations.
CONCLUSIONS:
Gigantol extracted from D. chrysotoxum Lindl not only has inhibitory effects on aldose reductase, but also inhibits AR gene expression. These findings provide a more comprehensive theoretical basis for the use of Dendrobium for the treatment of diabetic cataract.

Evid Based Complement Alternat Med. 2015;2015:350410.

Cytotoxic and Antimigratory Activities of Phenolic Compounds from Dendrobium brymerianum.[Pubmed: 25685168 ]

Chromatographic separation of a methanol extract prepared from the whole plant of Dendrobium brymerianum led to the isolation of eight phenolic compounds.
METHODS AND RESULTS:
Among the isolated compounds (1-8), moscatilin (1), Gigantol (3), lusianthridin (4), and dendroflorin (6) showed appreciable cytotoxicity against human lung cancer cell lines with IC50 values of 196.7, 23.4, 65.0, and 125.8 μg/mL, respectively, and exhibited antimigratory property at nontoxic concentrations.
CONCLUSIONS:
This study is the first report on the biological activities of this plant.

Mol Med Rep. 2018 Feb;17(2):3267-3273.

Protective effect of gigantol against hydrogen peroxide‑induced apoptosis in rat bone marrow mesenchymal stem cells through the PI3K/Akt pathway.[Pubmed: 29257286]

Bone marrow mesenchymal stem cell (BMSC) transplants are promising for the treatment of certain central nervous system diseases. However, oxidative stress is one of the major factors that may limit the survival of the transplanted BMSCs.
METHODS AND RESULTS:
The present study investigated the effect of pretreatment with Gigantol on hydrogen peroxide (H2O2)‑induced apoptosis in rat BMSCs (rBMSCs) and the potential underlying mechanisms. The results demonstrated that Gigantol pretreatment significantly inhibited H2O2‑induced apoptosis of rBMSCs. rBMSCs were incubated with 600 μM H2O2 in the absence or presence of different doses of Gigantol (1‑100 μM). Cell viability and apoptosis ratios were assessed by MTT assays and flow cytometry, respectively. Morphological alterations and reactive oxygen species were measured by the fluorescent‑based methods of Hoechst staining and dichlorodihydrofluorescein diacetate, respectively. Furthermore, the protein levels of phosphorylated‑protein kinase B (Akt), B‑cell lymphoma‑2 (Bcl‑2), Bcl‑2‑associated X (Bax), caspase‑3 and caspase‑9 were investigated by western blotting. Following incubation with H2O2 for 2 h, Gigantol significantly inhibited the H2O2‑induced reductions in the cell viability of rBMSCs in a dose‑dependent manner. Furthermore, Gigantol upregulated Akt phosphorylation and Bcl‑2 expression, downregulated Bax expression, and reduced the expression of caspase‑3 and caspase‑9 in H2O2‑treated rBMSCs, whereas an opposite effect was detected when LY294002, an inhibitor of phosphatidylinositol 3‑kinase, was administered in combination with Gigantol.
CONCLUSIONS:
These results indicate that Gigantol may be developed as a promising neuroprotective agent for successful MSC transplantation in ischemic diseases.

Oncol Rep. 2017 Feb;37(2):865-870.

Gigantol attenuates the proliferation of human liver cancer HepG2 cells through the PI3K/Akt/NF-κB signaling pathway.[Pubmed: 27959444]

Gigantol is a phenolic substance extracted from plants in the genus Dendrobium and used in traditional Chinese medicine. In the present study, we aimed to investigate the growth inhibition and apoptotic effects of Gigantol on human liver cancer cells through the PI3K/Akt/NF-κB signaling pathway.
METHODS AND RESULTS:
HepG2 cells were treated with different concentrations of Gigantol (0-150 μM) for 12, 24 and 48 h. It was found that Gigantol significantly inhibited the proliferation and induced apoptosis of the HepG2 cells. The results of fluorescence micrographs showed that a 48-h treatment with Gigantol induced typical apoptotic morphological features, which were consistent with the flow cytometric analysis where 20% of apoptotic cells were detected in response to Gigantol treatment. In addition, western blot analysis indicated that Gigantol enhanced the activities of caspase-3, PARP and p53 and downregulated the expression of p-Akt/Akt.
CONCLUSIONS:
Collectively, the present data suggest that Gigantol induces growth inhibition and apoptosis of HepG2 cells via the PI3K/Akt/NF-κB signaling pathway.

Nat Prod Res. 2014;28(21):1900-5.

Isolation of α-glucosidase inhibitors including a new flavonol glycoside from Dendrobium devonianum.[Pubmed: 25189122]

METHODS AND RESULTS:
From the whole plant of Dendrobium devonianum, a new flavonol glycoside, 5-hydroxy-3-methoxy-flavone-7-O-[β-D-apiosyl-(1 → 6)]-β-D-glucoside, as well as 13 known compounds, was isolated. Their structures were identified based on extensive spectroscopic studies including HR-EI-MS, (1)H, (13)C NMR, DEPT, H-H COSY, HSQC, HMBC and NOESY spectra.
CONCLUSIONS:
The new compound and Gigantol were evaluated for their α-glucosidase inhibitory activity, and both displayed more potent α-glucosidase inhibitory activity than acarbose, one of the most potent α-glucosidase inhibitor drugs, with the inhibition rate of 43.4% and 36.7%, respectively, in the concentration of 437.5 μmol/L.