Sodium sulfate addition increases the bioresource of biologically active sulfated polysaccharides from Antrodia cinnamomea.

Fungal sulfated polysaccharides (SPS) have been used in the pharmaceutical industry. In this study, sodium sulfate was employed as an elicitor to induce stress on the mycelia of Antrodia cinnamomea for the biosynthesis of SPS with high sulfate content. Sodium sulfate treatments increased the yield of SPS to 4.46 % and increased the sulfate content to 6.8 mmol/g of SPS. SPS were extracted from A. cinnamomea cultured with 500 mM sodium sulfate; these SPSs are denoted as Na500. Na500 exhibited the highest sulfate content and dose-dependent inhibitory activity against LPS-induced production of macrophage interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin 1ß (IL-1ß). Mechanistically, Na500 hindered the phosphorylation of transforming growth factor-ß receptor II (TGFRII), extracellular signal-regulated kinases (ERK), and protein kinase B (AKT) expression. A purified 7.79 kDa galactoglucan, Na500 F3, augmented the anti-inflammation activity by inhibiting LPS-induced TGFß release. Additionally, Na500 F3 restrained the LPS-induced phosphorylation of p-38, ERK, AKT, and TGFRII in RAW264.7 cells. Na500 F3 impeded the proliferation of lung cancer H1975 cells by inhibiting the phosphorylation of focal adhesion kinase, ERK, and Slug. The anti-inflammation and anticancer properties of Antrodia SPS contribute to its health benefits, suggesting its utility in functional foods.

Advanced culture strategy shows varying bioactivities of sulfated polysaccharides of Poria cocos.

This study compares the bioactivity of six sulfated polysaccharides derived from glucose- and sucrose-feeding extracted from P. cocos. Anti-inflammatory potentials of these polysaccharides were evaluated by pretreating lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. Of the tested polysaccharides, the sulfated polysaccharide derived from sucrose-feeding at the concentration of 40 g/l (referred to as "suc 40") exhibited the highest anti-inflammatory activity, of 83 %, and 33 % inhibition of IL-6 and TNF-α secretion, respetively. It achieved this by inhibiting the p-38 and c-Jun N-terminal kinase (JNK) MAPK signaling pathways. On the other hand, the sulfated polysaccharide derived from glucose-feeding at a concentration of 20 g/l (referred to as "glc 20") demonstrated the greatest anti-lung cancer activity. This was achieved by inducing apoptotic-related molecules, such as poly (ADP-ribose) polymerase (PARP) and CHOP. Furthermore, glc 20 had the highest contents of sulfate, fucose, and mannose compared to the other tested polysaccharides. This suggests that the composition of monosaccharide residues are critical factors influencing the anti-inflammatory and anti-cancer activities of these sulfated polysaccharides. Overall, this study highlights the potential of sulfated polysaccharides derived from P. cocos to function as bioactive compounds with anti-inflammatory and anti-cancer properties.

Exopolysaccharide is the potential effector of Lactobacillus fermentum PS150, a hypnotic psychobiotic strain.

Psychobiotics are a class of probiotics that confer beneficial effects on the mental health of the host. We have previously reported hypnotic effects of a psychobiotic strain, Lactobacillus fermentum PS150 (PS150), which significantly shortens sleep latency in experimental mice, and effectively ameliorate sleep disturbances caused by either caffeine consumption or a novel environment. In the present study, we discovered a L. fermentum strain, GR1009, isolated from the same source of PS150, and found that GR1009 is phenotypically distinct but genetically similar to PS150. Compared with PS150, GR1009 have no significant hypnotic effects in the pentobarbital-induced sleep test in mice. In addition, we found that heat-killed PS150 exhibited hypnotic effects and altered the gut microbiota in a manner similar to live bacteria, suggesting that a heat-stable effector, such as exopolysaccharide (EPS), could be responsible for these effects. Our comparative genomics analysis also revealed distinct genetic characteristics in EPS biosynthesis between GR1009 and PS150. Furthermore, scanning electron microscopy imaging showed a sheet-like EPS structure in PS150, while GR1009 displayed no apparent EPS structure. Using the phenol-sulfate assay, we found that the sugar content value of the crude extract containing EPS (C-EPS) from PS150 was approximately five times higher than that of GR1009, indicating that GR1009 has a lower EPS production activity than PS150. Through the pentobarbital-induced sleep test, we confirmed the hypnotic effects of the C-EPS isolated from PS150, as evidenced by a significant reduction in sleep latency and recovery time following oral administration in mice. In summary, we utilized a comparative approach to delineate differences between PS150 and GR1009 and proposed that EPS may serve as a key factor that mediates the observed hypnotic effect.

A branched 2-O sulfated 1,3-/1,4-galactoglucan from Antrodia cinnamomea exhibits moderate antiproliferative and anti-inflammatory activities.

A sulfated galactoglucan (3-SS) was discovered in Antrodia cinnamomea with antiproliferative and anti-inflammatory activities. Chemical identification of 3-SS resulted in the determination of a partial repeat unit as a 2-O sulfated 1,3-/1,4-linked galactoglucan with a two-residual 1,6-O-ß-Glc branch on the 3-O position of a Glc. by monosaccharide analysis and 1D and 2D NMR spectroscopy. The anti-inflammation effects of 3-SS on RAW264.7 macrophage cells, such as IL-6 inhibition, restoration of LPS-induced IκB protein degradation, and inhibited LPS-induced TGFRII protein degradation, were confirmed to occur via AKT, ERK1/2, and p-38. In addition, 3-SS impaired the proliferation of H1975 lung cancer cells through EGFR/ERK/slug signaling. This is the first finding of 2-O sulfated 1,3-/1,4-galactoglucan with 1,6-ß-Glc branches with dual functions of anti-inflammatory and antiproliferative activities.

ZnF3, a sulfated polysaccharide from Antrodia cinnamomea, inhibits lung cancer cells via induction of apoptosis and activation of M1-like macrophage-induced cell death.

Sulfated polysaccharides (Ac-SPSs) of Antrodia cinnamomea present anti-cancer activity. However, the anti-cancer mechanism of Ac-SPSs is not fully understood and remains largely unexplored. In this study, we identify an Ac-SPS with 7.9 kDa, noted ZnF3, and aim to examine the dual anti-cancer functions of ZnF3 on inhibiting cancer cells and activating macrophages. A biological study shows that ZnF3 inhibits lung cancer cells by inducing subG1 population and apoptosis. ZnF3 downregulates the expression of TGFß receptor in lung cancer cells. In parallel, ZnF3 activates macrophages via induction of TNF-α and IL-6 secretion, NO production and phagocytosis. ZnF3 activates AKT/mTOR pathway and induces M1 type macrophage polarization. Cancer cells co-cultured with ZnF3-stimulated macrophages, leading to inhibition of lung cancer cells. This study demonstrates that ZnF3 not only directly inhibits cancer cells but also activates macrophages-mediated cytotoxic effect on cancer cells. Moreover, ZnF3 may be a supplement for suppressing lung cancer cells.

Biochemical characterization and anti-cancer activity of tangential flow filtration system assisted purification of fucoglucan from Laminaria japonica.

Polysaccharide from Laminaria japonica (LJPS) exhibits multiple biological functions. However, we found that crude LJPS doesn't show good anti-lung cancer activity in this study. We therefore used tangential flow filtration (TFF) system to optimize the anticancer activity of LJPS. We divided the crude LJPS into two fractions by TFF system with a 10 kDa filter and denoted as retentate (10K-R) and filtration (10K-F). The chemical assay revealed that the main molecular mass of 10K-R and 10K-F is about 985 and 3 kDa, respectively. The main components of 10K-R include fucose (19.3 %), and glucose (59.5 %); while glucose (88.6 %) is a major component of 10K-F. Biological functions showed that 10K-R but not 10K-F inhibited the viability and mobility of cancer cells. 10K-R downregulated expressions of transforming growth factor ß receptor and Slug, and inhibited intracellular signaling molecules, including FAK, AKT, ERK1/2, and Smad2. This study is the first concept to purify the polysaccharide by TFF system and showed the potential mechanism of 10K-R inhibited cancer cells.

SPS, a sulfated galactoglucan of Laetiporus sulphureus, exhibited anti-inflammatory activities.

Laetiporus sulphureus is an edible and medicinal mushroom. A sulfated galactoglucan (SPS) was isolated by the papain method. Polysaccharides (PS) were isolated by hot water and ethanol precipitation. The medium molecular weight SPS of 100 to 1000 kDa accounted for over half of the SPS mixture. Fucose, galactose, glucose, and mannose were the major monosaccharides in SPS and PS. The amount of sulfate in SPS was 1.09 mmol/g. SPS showed inhibition of tumor necrosis factor-α (TNF-α) release and reversed IκB degradation in LPS-induced RAW264.7 macrophages. The suppression of TNF-α secretion by SPS was through inhibiting the phosphorylation of AKT/extracellular signal-regulated kinases (ERK), p38, and c-Jun N-terminal kinase (JNK). A purified SPS, named SPS-3, was proven to inhibit the LPS-induced phosphorylation of AKT, ERK, and p-38 in RAW264.7 cells. The suppression of interleukin 6 (IL-6) and transforming growth factor beta (TGFß) secretion by PS was through inhibiting LPS-induced phosphorylation of p-38 and TGF-ß receptor II (TGFRII) signaling pathways. This study demonstrates that the isolated SPS and PS from L. sulphureus possessed good anti-inflammatory activity for dietary supplements and functional food.

Structural changes, and anti-inflammatory, anti-cancer potential of polysaccharides from multiple processing of Rehmannia glutinosa.

Polysaccharides play important roles in the bioactivities of Rehmannia glutinosa. This study examined the physiochemical structure and biological activity of the polysaccharides of R. glutinosa during nine steps of processing. Characteristic study showed galactose, glucose, and fructose were the major sugars in the polysaccharides. The percentage of the high-molecular weight polysaccharide increased after processing. In addition, polysaccharides from repeated steam and dry processing of R. glutinosa can effectively increase the anti-inflammatory activity. Secretions of tumor necrosis factor (TNF-α), interleukin (IL)-6, and transforming growth factor (TGF)ß after lipopolysaccharide (LPS) stimulation were detected in RAW264.7 macrophages because of its anti-inflammatory activity. RG-B9, a polysaccharide of the ninth steam and dry processing, showed the strongest inhibitory activity on bacterial LPS-induced macrophage IL-6 and TGFß production. Mechanically, RG-B9 down-regulated the phosphorylation of AKT/ERK. The anti-inflammation of RG-B9 involved AKT/ERK/JNK signaling. In addition, RG-B9 inhibited the viability of lung cancer cells via EGFR/AKT signaling.

Effect of carbohydrate-feeding strategy on the production, physiochemical changes, anti-inflammation activities of polysaccharides of Poria cocos.

The aim of this research was to physiochemically characterize the structure and study the pharmaceutical benefits of the polysaccharide (PS) produced by Poria cocos using two selected carbohydrates (sucrose, and potato dextrose broth) in the in vitro culture system. A direct dosage effect was shown as sucrose- or PDB-based medium on the PS yield of Paragalago cocos. Very low-molecular-weight PS (<1 kDa) were largely synthesized by sucrose and PDB feeding. Sucrose-feeding mycelia of P. cocos results in a direct dosage effect in the fructose component in the PS. Sucrose and PDB feeding increased the glucose content but decreased the galactose content of PS. This study examined the anti-inflammatory activities of PS in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. At 100 µg/mL and 50 µg/mL, PS from 10 g/L PDB- treatment, denoted as PDB 10, pretreatment showed maximal inhibition of TNF-α and IL-6 release, respectively. Mechanically, PDB10 attenuated IκB from degradation in LPS-induced macrophages, and down-regulated LPS-induced phosphorylation of ERK/AKT/p-38. PDB10 showed dose-dependent inhibition of the LPS induced TGFRII signaling pathways.

Structural sequencing and anti-inflammatory, anti-lung cancer activities of 1,4-α/ß-sulfomalonoglucan in Antrodia cinnamomea.

Antrodia cinnamomea is a precious Polyporaceous fungus with various bioactivities. This study reports the chemical identification and biological activities of sulfomalonoglucan, a sulfated polysaccharide (SPS), from the sodium sulfate enriched medium of the title fungus. The SPS-containing fraction was separated by gel filtration chromatography (GFC) to give the title SPS (denoted as Na10_SPS-F3). By analyzing the evidence for key inter-glycosidic linkages in the 1D and 2D NMR spectroscopic data, one possible repeat unit was proposed as: Na10_SPS-F3 inhibited the secretion of tumor necrosis factor (TNF-α) and interleukin (IL)-6 after lipopolysaccharide (LPS) stimulation in RAW264.7 macrophages. Mechanistically, Na10_SPS-F3 downregulated TGFRII also attenuated the LPS-induced IκB-α degradation. Moreover, Na10_SPS-F3 inhibited lung cancer cell H1975 EGFR/ERK signaling. This is the first paper reporting a 3-O-sulfomalonyl glucan (Na10_SPS-F3) with eight 1,4-ß-Glc moieties connected with ten 1,4-α-Glc moieties from Antrodia cinnamomea and its anti-inflammatory and anti-cancer activities.

Effects of sterol-type elicitors on biochemical characterization of polysaccharides from Antrodia cinnamomea.

Sterols play crucial roles in the physiological functions of organisms. In this study, we examined the chemical and biological effects of sterol type elicitors, including squalene, cholesterol and stigmasterol, on polysaccharides (PSs) of Antrodia cinnamomea. Characteristic studies revealed that squalene and stigmasterol effectively increased the glucose contents in PSs. Specifically, squalene not only induced glucose content but also increased fucose and mannose levels in PSs. However, cholesterol did not induce changes in sugar content in PSs. We further identified that high dose squalene significantly promoted 20% yield (w/w) of PSs as well as significantly increased the glucose, galactose and fucose contents. In addition, the major PSs species had a molecular weight of 21 kDa, and squalene significantly increased its area percentage to 43.54. The biological effects of PSs (squalenePS) from squalene treated A. cinnamomea presented anticancer activities by inhibiting lung cancer cell viability and colony formation. Functional studies revealed that squalenePS reduced the glucose uptake and lactate secretion may correlate to inhibition of AKT activity and downregulation of glucose transporter (GLUT1) expression. Our findings suggested squalene may play vital roles in regulating the PSs assembling and bioactivities of A. cinnamomea. Moreover, squalene may be a potential supplement for adding the culture medium of A. cinnamomea.

Production, characterization, and functions of sulfated polysaccharides from zinc sulfate enriched cultivation of Antrodia cinnamomea.

This research utilized zinc sulfate enriched cultural conditions to produce sulfated polysaccharides from Antrodia cinnamomea (denoted as ZnFSPS) and physiochemically characterize functional and mechanical investigations of ZnFSPS. The maximum SPS yield reached a value of 6.68% when A. cinnamomea was fed zinc sulfate with 250 mM (denoted as Zn250). Zn250 had a maximal inhibitory effect on LPS-induced tumor necrosis factor (TNF-α) release in RAW264.7 macrophage. Zn250 contained the highest area percentage of molecular weight of 178.5, 105.1, and 1.56 kDa at values of 19.08, 15.09, and 5.04. Zn250 contained three times the sulfate content as compared with the control. Mechanism studies revealed a novel finding that Zn250 inhibited the LPS-induced RAW264.7 macrophage inflammation and selectively blocked pAKT, pERK and p38. Zn250 also attenuated the LPS-induced IkB-α degradation. In addition, ZnFSPS interfered with lung cancer cell H1975 TGFRI/FAK/Slug signaling. These results suggest ZnFSPS plays roles in regulating inflammatory and anti-lung cancer activity.

Physiochemical changes and mechanisms of anti-inflammation effect of sulfated polysaccharides from ammonium sulfate feeding of Antrodia cinnamomea.

Antrodia cinnamomea is an important medicinal fungus in Taiwan. This study demonstrates changes of complex sulfated polysaccharides (SPS) by fungus A. cinnamomea after ammonium sulfate-feeding and evaluates its anti-inflammatory activities. The addition of 1 mM ammonium sulfate showed maximal sulfate content of SPS in value of 1.82 mmol/g. Ammonium sulfate changes the physiochemical properties of SPS in that area percentage of SPSs (361 kDa) was increased for 1 mM ammonium sulfate to the value of 26 percentage area. SPS of 1 mM ammonium sulfate-fed A. cinnamomea (AM-SPS) had maximal inhibition of LPS-induced tumor necrosis factor (TNF-α) release in RAW264.7 macrophage. Iκ-B degradation induced by LPS in macrophages was reversed by AM-SPS. Suppression of NF-κB activation might have been responsible for the anti-inflammatory effects. Meanwhile, the inhibition was also due to suppressing the AKT, and ERK signaling pathway. Our finding suggests that ammonium sulfate is a useful nutrient for production of SPS for neutraceutical and pharmaceutical applications.

Sodium thiosulfate enhances production of polysaccharides and anticancer activities of sulfated polysaccharides in Antrodia cinnamomea.

Sulfated polysaccharides (SPSs) are polysaccharides (PSs) with high sulfate functionalization and possess bioactivities. This study aimed to increase the sulfate content of SPSs in Antrodia cinnamomea through sulfate feeding. Feeding A. cinnamomea with sodium thiosulfate was found to increase yields of PSs and SPSs in A. cinnamomea. The SPSs thus obtained (ST-SPS) were further isolated, showing enhanced sulfate content of 2.5 mmol/g. Sodium thiosulfate induced changes in molecular weight from 320 kDa to 1342 kDa, and area percentage of low-molecular-weight ST-SPS (< 20 kDa) was decreased. Functional studies revealed that sodium thiosulfate increased the ST-SPS anticancer efficacy in cancer cells via inhibition of EGFR/AKT signaling. Moreover, the ST-SPS enhanced synergistically cisplatin-, gefitinib- and 5 FU-induced cytotoxic effects in lung cancer H1975 cells and colon cancer CT26 cells. This study is the first to demonstrate that sodium thiosulfate induced changes in properties of A. cinnamomea with the anticancer mechanisms of ST-SPS.

A sulfated glucan from Antrodia cinnamomea reduces Slug expression through regulation of TGFß/AKT/GSK3ß axis in lung cancer.

SGA is a sulfated glucan from Antrodia cinnamomea. In this study, we showed that SGA suppressed tumor growth in vitro and in vivo. SGA also potentiated cisplatin-induced cytotoxicity in lung cancer cells. TGFß signaling and overexpression of Slug are regarded as the critical events in lung tumor malignancy. Functional studies revealed that SGA inhibited the TGFß/FAK/AKT axis by inducing lipid-raft-mediated lysosome-dependent TGFß receptor degradation, resulting in suppressing cancer cell viability and migration. Moreover, SGA elimination of TGFß-mediated intracellular signaling promoted Slug degradation in H1975 cells. Mechanistically, we demonstrated that proteasome-dependent Slug degradation was controlled by TGFß-mediated downstream signaling pathways; however, inhibitors of AKT and GSK3 abolished Slug degradation. Our findings suggested that SGA targets of the TGFß/AKT/GSK3ß axis played a key role in enhancing Slug degradation and suppressing lung cancer cells. In addition, SGA may be a potential therapeutic supplement for lung cancer.

Microelements induce changes in characterization of sulfated polysaccharides from Antrodia cinnamomea.

Microelements play pivotal roles for fungal/plant development and end-use properties. In this study, we examined the production and characterization of valuable sulfated polysaccharides (SPSs) with biological benefits from Antrodia cinnamomea and fine-tuning of mycelial culture conditions. Using various sulfated salts (e.g. CuSO4, FeSO4 and ZnSO4) to feed A. cinnamomea, we found that CuSO4 and ZnSO4 increased 25% and 20% of mycelium yields, respectively. We further isolated the SPSs from CuSO4, FeSO4 and ZnSO4-feeding of A. cinnamomea (called CuFSPS, FeFSPS and ZnFSPS, respectively) and found that CuSO4 and ZnSO4 significantly promoted SPS production. By contrast, FeSO4 did not change the yields of mycelium and SPS from A. cinnamomea. Characteristic studies have revealed that these sulfated salts did not significantly induce change in the sulfation and the sugar contents of SPS. However, the galactose and glucose contents in ZnFSPS were increased to the value of 249 and 1038 µmol/g, respectively. In addition, in regard to area percentages, while the major SPSs species were low-molecular-weight SPSs (<23 kDa), the sulfated salts increased the area percentages of molecular size in the range of 200-500 kDa. Anticancer function studies showed that those SPSs inhibit the cell viability 35-45% at 800 µg/ml of lung cancer A549 cells via downregulation of EGFR signaling. Our study is the first to identify the efficacy of microelements in the enhancement of mycelia yield and SPS, in which CuSO4 and ZnSO4 enhanced mycelia growth and increased the production of SPS. Our finding suggests that ZnSO4 may play roles in regulating the SPS assembling. Moreover, those SPSs derived from feeding A. cinnamomea with microelements may be useful as a potential agent for inhibition of lung cancer viability.

Large-scale preparation of sulfated polysaccharides with anti-angionenic and anti-inflammatory properties from Antrodia cinnamomia.

Sulfated polysaccharides (SPSs) were isolated from 0.5mM potassium-sulfate fed Antrodia cinnamomea. We investigated the chemical properties and bio-activities of the five different fractions (SPS-K1, SPS-K2, SPS-K3, SPS-K4, and SPS-K5) with molecular weights ranging from 0.51 to 523.48kDa. SPS-K3 was consisted mainly of glucose, galactose and sulfate in a molar ratio of 15:1:30 with Mn value of 6.82kDa. It showed maximal inhibition of the tumor necrosis factor (TNF-α), interleukin-1beta (IL-1ß) and interleukin-6 (IL-6) on bacterial LPS-induced inflammation in RAW264.7 macrophage and the production was recorded as 26.19 and 51.06%, respectively. SPS-K2 showed inhibition of endothelial cell tube formation in an in vitro assay of angiogenesis, and IC50 was determined to be 160.92µg/ml. Large-scale preparation of SPS was performed in the 3-L fermentation of A. cinnamomea and the yield of the SPS was 5.38%. The area percentage of high-molecular-weight SPSs (1470-1590kDa) covered almost half of the SPSs mixture characterized by size exclusion column chromatography. The SPSs from fermented A. cinnamomea had significant inhibition on TNF-α, IL-1ß and IL-6 production. This study is the first report to large-scale produce SPSs and demonstrates sulfated galactoglucan with strong anti-inflammatory activity.

Characterization of a sulfated galactoglucan from Antrodia cinnamomea and its anticancer mechanism via TGFß/FAK/Slug axis suppression.

A sulfated 1,4-ß-d-galactoglucan (B86-III) with 1,6-branches was isolated and identified from Antrodia cinnamomea. The repeating unit of B86-III was proposed based on one-dimensional 1D (1H, 13C and DEPT-135) and 2D (DQF-COSY, TOCSY, HSQC and HMBC) NMR spectra. The conformation of the sugars was hypothesized to be a rare boat form instead of a 4C1 chair form. The sulfate substitutions were suggested to be on the C-2 and C-3 positions, resulting in the following structure: B86-III inhibited the viability of H1975 lung cancer cells via cell apoptosis, including the activation of caspase 3 and PARP. Transforming growth factor ß receptor (TGFR) and its downstream signaling FAK and Slug are involved in lung tumorigenesis. B86-III downregulated TGFR I protein levels and inhibited FAK phosphorylation, resulting in inhibition of Slug expression and migration. This study is the first to characterize sulfated polysaccharides with a rare boat-form conformation and identify the mechanism of inhibition lung cancer cell.

Molecular mechanism of Antrodia cinnamomea sulfated polysaccharide on the suppression of lung cancer cell growth and migration via induction of transforming growth factor ß receptor degradation.

A sulfated polysaccharide of edible mushroom Antrodia cinnamomea (SPS) has been identified as a novel immunomodulatory agent. We examined the anti-cancer effects of SPS by conducting a series of in vitro studies. We found that SPS inhibits the growth of A549 and LLC1 lung cancer cells via the induction of cell cycle arrest and activation of caspase 3 and PARP. By contrast, we found that a non-sulfated polysaccharide of A. cinnamomea (NSPS) does not inhibit lung cancer cell viability. Moreover, NSPS does not induce changes in cell cycle distribution or activate apoptosis-related molecules in both A549 and LLC1 cells. High expression of transforming growth factor ß (TGFß) and TGFß receptors (TGFRs) is correlated with lung tumorigenesis. SPS suppresses TGFß-induced intracellular signaling events, including phosphorylation of Smad2/3, FAK, Akt, and cell migration. By contrast, non-sulfated polysaccharide (NSPS) does not exhibit the similar biological functions in both A549 and LLC1 cells. Mechanistically, we demonstrated SPS effectively reduces TGFR protein levels via induction of proteasome-dependent degradation pathway. Our study is the first to identify the pivotal role of SPS in the induction of TGFR degradation and activation of Caspase 3 and PARP, which leads to suppress viability and migration of lung cancer cells.