Dextrans, Pullulan and Lentinan, New Scaffold Materials for Use as Hydrogels in Tissue Engineering.

The development of hydrogels based on dextrans, pullulan and lentinan to be used in biomedical applications including tissue engineering is reported. Despite the fact that selected polysaccharides such as hyaluronic acid are well established, little is known, how these polysaccharides can be chemically modified to create hydrogels under controlled conditions. In this study we present a small library of chemically modified polysaccharides which are used for a divergent approach to achieve biomedical relevant hydrogels. In this case the crosslinking is based on thio ether formation between thiol modified donor and vinylsulfone or maleimide modified acceptor components. Successful synthesis of the linker systems and coupling at the polysaccharides, hydrogel formation takes place under physiological conditions. We extended the study by coupling small molecules like adhesion factors for increasing cell compatibility as well as a dye for further studies. The different hydrogels were studied to their rheological properties, water uptake, their permeability, biodegrability and their cytotoxicity.

Lentinan alleviates sciatic nerve injury by promoting autophagy to remove myelin fragments.

Lentinan, a natural drug with wide-ranging pharmacological activities, can regulate autophagy-the process through which Schwann cells (SCs) eliminate myelin fragments after peripheral nerve injury (PNI). However, the effect of lentinan after PNI and the role of accelerated myelin debris removal via autophagy in this process are unclear. This study examined the effect of lentinan on rat sciatic nerve repair following crush injury and the underlying mechanisms. After the successful establishment of the sciatic nerve compression injury model, group-specific treatments were performed. The treatment group received 20 mg/kg lentinan via intraperitoneal injection, while the model group was treated with normal saline. The recovery in each group was then evaluated. Further, a rat SC line (RSC96) was cultured in medium with/without lentinan after supplementation with homogenous myelin fractions to evaluate the removal of myelin particles. Our results showed that lentinan promotes autophagic flux in vivo via the AMPK/mTOR signaling pathway, accelerates the clearance of myelin debris by SCs, and inhibits neuronal apoptosis, thereby promoting neurological recovery. Similarly, in vitro experiments showed that lentinan promotes the phagocytosis of myelin debris by SCs. In conclusion, our results suggest that lentinan primarily promotes nerve regeneration by accelerating the autophagic clearance of myelin debris in SCs, and this process is likely regulated by the AMPK/mTOR signaling pathway. Therefore, this study provides compelling evidence that lentinan may be a cost-effective and natural treatment agent for PNI.

Effect of lentinan on proliferation and apoptosis of human astrocytoma U251 cells.

AIM OF THE STUDY: Aim of the study is To investigate the effect of lentinan on proliferation and apoptosis of human astrocytoma U251 cells. Lentinan was dissolved in DMEM complete medium to form different concentrations (0, 25, 50, 100, 200, 400, 500, 600 µg/ml). CCK8 was used to detect the effect of lentinan with different concentrations on proliferation of human astrocytoma U251 cells, and the expression of Ki-67 was detected by immunofluorescence. In addition, the effect of different concentrations of lentinan on apoptosis of human astrocytoma U251 cells was detected by flow cytometry. Compared with the blank control group, 50 and 100 µg/ml lentinan significantly promoted proliferation of human astrocytoma U251 cells. When the concentration is more than 100 µg/ml, the cell activity gradually decreases, and the cell activity is the lowest when the concentration is 600 µg/ml. In addition, the low concentration lentinan (25, 50, and 100 µg/ml) had no significant effect on apoptosis of human astrocytoma U251 cells. However, lentinan above 200 µg/ml significantly promoted apoptosis of human astrocytoma U251 cells and had a concentration gradient effect, and the highest apoptosis rate was at 600 µg/ml. CONCLUSIONS: Lentinan can effectively inhibit proliferation and promote apoptosis of human astrocytoma U251 cells.

Effect of lentinan on gelling properties and structural changes of goose myofibrillar protein under oxidative stress.

BACKGROUND: The reduction of protein oxidation is important for maintaining the product quality of reconstituted meat. In this study, the dose-dependent effects of lentinan (LNT) on gelling properties and chemical changes in oxidatively stressed goose myofibrillar protein were investigated. RESULTS: Myofibrillar protein (MP) with 200 µmol g-1 protein LNT increased gel strength by 87.90 ± 9.26% in comparison with LNT-free myofibrillar protein after oxidation. Scanning electron microscopy analysis revealed that the gel network containing LNT was compact, with small pores and uniform distribution. The absolute value of the zeta potential reduced significantly following oxidation of LNT with 200 µmol g-1 protein at 4 °C for 12 h compared with the zeta potential without LNT, according to the laser particle size analyzer. The incorporation of LNT increased protein solubility and -SH content, inhibited carbonyl formation, enhanced α-helix content and tryptophan intrinsic fluorescence intensity, and reduced exposure of hydrophobic groups and protein aggregation. CONCLUSION: The results indicated that adding LNT to myofibrillar protein could improve gel. This is related to its protective effect on conformational changes in the oxidation system. Lentinan is therefore recommended for oxidatively stressed goose meat processing to enhance the MP gelling potential. © 2023 Society of Chemical Industry.

Lentinan enhances the antitumor effects of Delta-like 1 via neutrophils.

BACKGROUND: Selective activation of Delta-like 1 (DLL1)-Notch signaling is a new approach to activate CD8+ T cell and suppress tumor growth, while the efficacy remains modest. Lentinan (LNT) is a clinically used immunomodulation agent. Thus, we hypothesized that LNT could improve the efficacy of DLL1. METHODS: The effects of LNT combined with DLL1 on tumor growth were evaluated by growth curve and tumor weight in EO771 breast and LAP0297 lung tumor models. The impacts on immune cells and gene expression in tumor tissues were determined by flow cytometry, qPCR. Neutrophil depletion was used to investigate the mechanism of the combination therapy on tumor growth. The data sets were compared using unpaired student's t-test or ordinary one-way ANOVA. RESULTS:  LNT treatments additively improved the antitumor effects of DLL1 in EO771 breast tumor growth. Remarkably, LNT treatments synergistically enhanced the suppression of DLL1 on LAP0297 lung tumor growth, resulting in tumor regression. Mechanically, the combination of LNT and DLL1 interventions not only promoted the accumulation and activation of CD8+ T cells, but also increased intratumoral CD45+CD11b+Ly6G+ neutrophils. Reduced neutrophils by anti-Gr1 antibody administrations reversed the improved antitumor effects by LNT treatments in LAP0297 lung tumor. These results suggest that LNT treatments improve the inhibition of DLL1 on tumor growth via neutrophils. CONCLUSIONS: Our findings indicates that LNT and DLL1 may induce synergistical antitumor immunity via simultaneous modulating lymphoid and myeloid cell populations regardless of the type of tumor, providing a potential new strategy to potentiate cancer immunotherapy.

Lentinan triggers oxidative stress-mediated anti-inflammatory responses in lung cancer cells.

Inflammatory responses change several aspects of malignancies such as proliferation, survival, angiogenesis, and metastasis and lead to tumor progression. Lung cancer is the leading type of cancer worldwide and cancer-related inflammatory mediators challenge the successful treatments. Lentinan, a polysaccharide derived from Lentinula edodes, has shown anti-inflammatory characteristics in colitis and has been approved as an adjuvant therapy for cancer treatment. In the present study, we explored the mechanism underlying anti-inflammatory function of Lentinan in lung cancer cells. We showed that Lentinan reduced the inflammatory cytokines IL-6 and IL-1ß in LPS-stimulated A549 cells at the concentrations much lower than the IC50. Lentinan failed to alter the NLRP3 expression profile at transcriptional and translational levels. However, it showed a huge inhibition of caspase-1 activity. Lentinan downregulated the expression of IL-6 and IL-1ß at the mRNA level. We also showed that Lentinan altered the oxidative status of the cells by increasing the intracellular ROS content and attenuating the activity of GPx4, the key player in the anti-oxidative defense system. Lentinan-induced ROS generation was associated with caspase-3 activation and induction of DNA breaks. This alteration was also associated with mitochondrial membrane depolarization shown by TMRE staining. Using recombinant caspase-1, we showed that Lentinan did not directly target caspase-1 but it led to caspase-1 inhibition. In conclusion, cytotoxicity and anti-inflammatory functions are separated by the dose of Lentinan. Lentinan increased the ROS and mitochondrial dysfunction in a level that is insufficient to induce cell death, but is sufficient to regulate the NLRP3 activation.

Immunogenic Cell Death (ICD) of Murine H22 Cells Induced by Lentinan.

Lentinan can lead to apoptosis of tumor cells and improve immune function. However, limited research focused on the immunogenic death regulation mechanism of lentinan on mouse H22 cells. The study aimed to explore the effect of Lentinan on the expression of immunogenic death-related proteins in mice H22 cells. MTT method was used to detect and evaluate the effect of 200-1000 µg/mL lentinan on the survival rate of H22 cells after 24 h, 48 h, and 72 h, respectively. Flow cytometry was employed to collect the apoptotic rate of lentinan at different concentrations (200-800µg/mL) on H22 cells for 48 h, and obtain the apoptotic rate of 600 µg/mL lentinan at different times (12-72 h). The effect of Lentinan on the expression of H22 Immunogenic Cell Death proteins was analyzed by ELISA and HPLC-MS afterward. Results suggest that lentinan cytotoxic and pro-apoptotic have a concentration-dependent manner with the H22 cells. Moreover, the rate of apoptosis increased significantly (P < 0.05) in 24 h. Lentinan can induce the expression of Calreticulin(CRT), High mobility protein 1(HMGB1), ATP and Heat shock protein 70 (HSP70) .Therefore, the antitumor effect of lentinan may be related to the regulation of immunogenic death-related protein expression, which was beneficial to the future development of liver cancer vaccines.

Interactive Effect of Biological Agents Chitosan, Lentinan and Ningnanmycin on Papaya Ringspot Virus Resistance in Papaya (Carica papaya L.).

The papaya industry is mainly impacted by viral diseases, especially papaya ringspot disease (PRSD) caused by papaya ringspot virus (PRSV). So far, research on the interaction between Chitosan, Lentinan and Ningnanmycin on PRSD has not been reported. This research studied the controlled and interactive effect of three biological agents, namely, Chitosan (C), Lentinan (L) and Ningnanmycin (N), on PRSV in papaya, individually and collectively. The changes in disease index, controlled effect, Peroxidase (POD), Polyphenol oxidase (PPO), Superoxide dismutase (SOD), growth and development of plants were observed at the seedling stage, in pots, and at the fruiting stage, in the field. The appearance and nutrient contents of fruits were measured during the fruit stage. The disease index of PRSV, at seedling and fruiting stages, was significantly lower for chitosan, lentinan and ningnanmycin and their interactive effect, compared to a control check treatment. The activity of the defense enzymes could be improved by the three kinds of biological agents and their interactive effect, especially lentinan and ningnanmycin. The chlorophyll content, plant height, stem diameter and fruit quality rose significantly under chitosan, lentinan and ningnanmycin treatments. The interaction of LN could inhibit PRSV disease at the seedling and fruiting stages of papaya, and promote the growth of plants and the quality of fruit at the fruit stage. Hence, this study provides the theoretical foundation for the biological control of papaya ringspot disease.

Apaf1 nanoLuc biosensors identified lentinan as a potent synergizer of cisplatin in targeting hepatocellular carcinoma cells.

Liver cancer is one of the most common malignancies that is difficult to treat due to late diagnosis and chemo-resistance. In the present study, we developed and validated a cell based split nanoLuc biosensor to monitor the Apaf1-Apaf1 interactions in response to apoptosis-inducing drugs such as cisplatin. We showed that the activity of split nanoLuc is reconstituted only in response to apoptotic inducer, cisplatin and in a dose-dependent manner. Apaf1 mutants which were unable to oligomerize failed to recover nanoLuc activity while constitutively active variant increased the nanoLuc activity. Generation of Apaf1 knockout HepG2 and treatment with cisplatin showed dramatic reduction in cell death suggesting that cisplatin mainly targets liver cancer cells through apoptosis. As the natural products are potent sources of compounds for adjuvant therapy, we screened a collection of natural products and identified lentinan as an inducer of apoptosome formation, a key step for induction of apoptosis. Lentinan is a polysaccharide with antitumor, pro-apoptotic properties that functions with poorly understood mechanisms. Lentinan was shown to have cytotoxic effects with the IC50 of 650 µM. Sub-lethal lentinan concentration doubled the nanoLuc activity when co-treated with cisplatin. We also showed that lentinan hugely reduced the dose of cisplatin to induce certain amount of death and that lentinan co-treatment with cisplatin enhanced the Apaf1 transcription in HepG2 cells while lentinan or cisplatin alone failed to alter the transcription. In addition, lentinan and cisplatin co-treatment induced mitochondrial depolarization. This suggested that lentinan combinatorial therapy with cisplatin engaged a different signalling pathway to kill the liver cancer cells and that adjuvant therapy with lentinan can reduce the dose of cisplatin and thus reduce the possibility of chemo-resistance.

Lentinan Inhibited the Activation of Th2 Cells in Allergic Mice by Reducing the Amplitude of Changes in Biological Rhythm.

INTRODUCTION: Biological rhythm is inextricably linked to the physiological mechanisms of allergic diseases, but the exact mechanisms are still poorly understood. Clinical studies have reported rhythmic fluctuations in allergic diseases. The search for natural and harmless active ingredients based on biological rhythm with which to regulate allergic diseases is essential for the control of food allergy. METHODS: In this study, mice were treated at different time points to determine the link between the severity of allergic reactions and the circadian clock genes. The mice were treated with lentinan, either continuously or discontinuously, to assess their clinical symptoms, vascular permeability, immune cells, cytokines, and clock genes. Specifically, rat basophilic leukemia (RBL-2H3) cells were treated with lentinan and the rhythmic changes of cell degranulation were measured. RESULTS: The results in different models showed that the allergic reactions in mice treated at different time points were significantly different and thus related to fluctuations in biological rhythm. Treatment with lentinan was found to reduce the amplitude of changes in the clock genes, such as the activation of Per and Cry proteins in allergic mice, as well as to regulate biological rhythm in cells, inhibit the activation of Th2 cells, and alleviate allergic reactions. Furthermore, lentinan changed the rhythm of degranulation in RBL-2H3 cells. CONCLUSION: Lentinan was, therefore, determined to successfully alleviate allergic reactions by reducing the amplitude of changes in the body's biological rhythm, inhibiting the activation of Th2 cells, and affecting the immune microenvironment.

Not a fungi to be with: Shiitake mushroom flagellate dermatitis.

Shiitake dermatitis is a rare adverse cutaneous reaction to the ingestion of raw or undercooked shiitake mushrooms (Lentinula edodes). We report the case of a patient who developed a striking linear flagellate dermatitis without urticaria three days after returning from a trip from Tokyo where he had eaten shiitake mushrooms. The rash resolved after two weeks with topical corticosteroids and antihistamines given for symptomatic relief. Shiitake dermatitis is thought to be either a toxic or hypersensitivity reaction to lentinan, a heat-inactivated polysaccharide found in the cell walls of shiitake mushrooms. Although this mushroom is widely consumed in Eastern Asia, with the increasing globalisation of cuisine and travel, cases are likely to become more common in the Western world.

Purified ß-glucans from the Shiitake mushroom ameliorates antibiotic-resistant Klebsiella pneumoniae-induced pulmonary sepsis.

Bacterial infection remains the main cause of acute respiratory distress syndrome and is a leading cause of death and disability in critically ill patients. Here we report on the use of purified ß-glucan (lentinan) extracts from Lentinus edodes (Shiitake) mushroom that can reduce infection by a multidrug-resistant clinical isolate of Klebsiella pneumoniae in a rodent pneumonia model, likely through immunomodulation. Adult male Sprague-Dawley rats were subjected to intra-tracheal administration of K. pneumoniae to induce pulmonary sepsis and randomized to three groups; vehicle control (Vehicle, n = 12), commercial lentinan (CL, n = 8) or in-house extracted lentinan (IHL, n = 8) were administered intravenously 1 h postinfection. Physiological parameters and blood gas analysis were measured, bacterial counts from bronchoalveolar-lavage (BAL) were determined, along with differential staining of white cells and measurement of protein concentration in BAL 48 h after pneumonia induction. Use of IHL extract significantly decreased BAL CFU counts. Both CL and IHL extractions reduced protein concentration in BAL. Use of IHL resulted in an improvement in physiological parameters compared to controls and CL. In conclusion, administration of lentinan to treat sepsis-induced lung injury appears safe and effective and may exert its effects in an immunomodulatory manner.

Therapeutic effects of lentinan on inflammatory bowel disease and colitis-associated cancer.

In this study, we investigated the therapeutic potential of lentinan in mouse models of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Lentinan decreased the disease activity index and macroscopic and microscopic colon tissue damage in dextran sulphate sodium (DSS)-induced or TNBS-induced models of colitis. High-dose lentinan was more effective than salicylazosulfapyridine in the mouse models of colitis. Lentinan decreased the number of tumours, inflammatory cell infiltration, atypical hyperplasia and nuclear atypia in azoxymethane/DSS-induced CAC model. It also decreased the expression of pro-inflammatory cytokines, such as IL-13 and CD30L, in IBD and CAC model mice possibly by inhibiting Toll-like receptor 4 (TLR4)/NF-κB signalling and the expression of colon cancer markers, such as carcinoembryonic antigen, cytokeratin 8, CK18 and p53, in CAC model mice. In addition, lentinan restored the intestinal bacterial microbiotal community structure in IBD model mice. Thus, it shows therapeutic potential in IBD and CAC model mice possibly by inhibiting TLR4/NF-κB signalling-mediated inflammatory responses and disruption of the intestinal microbiotal structure.

[Reflectance confocal microscopy in Shiitake dermatitis]. / Konfokale Lasermikroskopie bei Shiitake-Dermatitis.

Shiitake dermatitis usually occurs 1-2 days after consumption of incompletely cooked or raw shiitake mushrooms and is characterized by linear, pruritic, erythematous papulovesicular rashes. It is caused by lentinan, a polysaccharide component of the cell walls of shiitake mushrooms. The histological examination showed an eczema-like morphology with spongiosis and lymphohistiocytic infiltrates. The results of reflectance confocal microscopy (RCM) correlated with the histopathological investigations. Therefore, RCM can be used for non-invasive diagnostic confirmation of Shiitake dermatitis in the future.

Selenium-lentinan inhibits tumor progression by regulating epithelial-mesenchymal transition.

BACKGROUND: Selenium supplementation can be used to treat tumors. However, inorganic selenium is highly toxic, and natural organic selenium is extremely rare. Polysaccharides can improve drug bioavailability and targeting. Lentinan is a polysaccharide that has been approved as an anti-cancer drug in Japan and China. METHODS: Lentinan, an antitumor polysaccharide extracted from Lentinus edodes, was conjugated with seleninic acid to be transformed into ester (Se-lentinan) and utilized as drug carrier. The enhancement of the anti-tumor effects of Se-lentinan was evaluated by cell viability, cell cycle, migration, and transwell assays and animal xenograft models. The effects of Se-lentinan on the expression levels of epithelial-mesenchymal transition (EMT) markers were determined through immunofluorescence, Western blot, and immunohistochemistry analyses. RESULTS: Se-lentinan inhibited the invasiveness of B16-BL6 and HCT-8 cells by suppressing EMT. In vivo, Se-lentinan significantly inhibited tumor growth and metastasis of the transplanted melanoma and colon cancer cells and showed less toxicity than sodium selenite. Moreover, Se-lentinan reduced the accumulation of selenium in the liver and kidney tissues of mice and exhibited low organ toxicity. CONCLUSION: The antitumor activity of selenium was enhanced greatly, and its side effects were reduced with the use of lentinan as drug carrier.

Sulfated lentinan induced mitochondrial dysfunction leads to programmed cell death of tobacco BY-2 cells.

Sulphated lentinan (sLTN) is known to act as a resistance inducer by causing programmed cell death (PCD) in tobacco suspension cells. However, the underlying mechanism of this effect is largely unknown. Using tobacco BY-2 cell model, morphological and biochemical studies revealed that mitochondrial reactive oxygen species (ROS) production and mitochondrial dysfunction contribute to sLNT induced PCD. Cell viability, and HO/PI fluorescence imaging and TUNEL assays confirmed a typical cell death process caused by sLNT. Acetylsalicylic acid (an ROS scavenger), diphenylene iodonium (an inhibitor of NADPH oxidases) and protonophore carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (a protonophore and an uncoupler of mitochondrial oxidative phosphorylation) inhibited sLNT-induced H2O2 generation and cell death, suggesting that ROS generation linked, at least partly, to a mitochondrial dysfunction and caspase-like activation. This conclusion was further confirmed by double-stained cells with the mitochondria-specific marker MitoTracker RedCMXRos and the ROS probe H2DCFDA. Moreover, the sLNT-induced PCD of BY-2 cells required cellular metabolism as up-regulation of the AOX family gene transcripts and induction of the SA biosynthesis, the TCA cycle, and miETC related genes were observed. It is concluded that mitochondria play an essential role in the signaling pathway of sLNT-induced ROS generation, which possibly provided new insight into the sLNT-mediated antiviral response, including PCD.

Lentinan protects pancreatic ß cells from STZ-induced damage.

Pancreatic ß-cell death or dysfunction mediated by oxidative stress underlies the development and progression of diabetes mellitus (DM). In this study, we evaluated the effect of lentinan (LNT), an active ingredient purified from the bodies of Lentinus edodes, on pancreatic ß-cell apoptosis and dysfunction caused by streptozotocin (STZ) and the possible mechanisms implicated. The rat insulinoma cell line INS-1 were pre-treated with the indicated concentration of LNT for 30 min. and then incubated for 24 hrs with or without 0.5 mM STZ. We found that STZ treatment causes apoptosis of INS-1 cells by enhancement of intracellular reactive oxygen species (ROS) accumulation, inducible nitric oxide synthase (iNOS) expression and nitric oxide release and activation of the c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signalling pathways. However, LNT significantly increased cell viability and effectively attenuated STZ-induced ROS production, iNOS expression and nitric oxide release and the activation of JNK and p38 MAPK in a dose-dependent manner in vitro. Moreover, LNT dose-dependently prevented STZ-induced inhibition of insulin synthesis by blocking the activation of nuclear factor kappa beta and increasing the level of Pdx-1 in INS-1 cells. Together these findings suggest that LNT could protect against pancreatic ß-cell apoptosis and dysfunction caused by STZ and therefore may be a potential pharmacological agent for preventing pancreatic ß-cell damage caused by oxidative stress associated with diabetes.

Immunoprotective effect of lentinan in combination with miltefosine on Leishmania-infected J-774A.1 macrophages.

Rejuvenation of deteriorated host immune functions is imperative for successful annihilation of Leishmania parasites. The use of immunomodulatory agents may have several advantages as they conquer immunosuppression and, when given in combination, improve current therapeutic regimens. We herein investigated the immunostimulatory potency of a ß-glucan, lentinan either alone or in combination with short dose of standard drug, miltefosine on Leishmania-infected J-774A.1 macrophages. Our study shows that infected macrophages when stimulated with 2.5 µg/mL and above concentrations of lentinan secreted significant amount of host-protective molecules. The in vitro interaction between lentinan and miltefosine showed some synergy (mean sum of fractional inhibitory concentration [mean ∑FIC] 0.87) at IC50 level. Lentinan (2.5 µg/mL) plus low-dose miltefosine (2 µM) displayed heightened level of pro-inflammatory cytokines, IL-12 (13.6-fold) and TNF-α (6.8-fold) along with nitric oxide (7.2-fold higher) when compared with infected control. In combination group, we also observed remarkably (P<.001) suppressed levels of anti-inflammatory cytokines, IL-10 and TGF-ß, than that of untreated macrophages. Additionally, in comparison with infected group, we observed significant induction in phagocytic activity of macrophages in combination with treated group. Collectively, these findings emphasize the immunostimulatory effect of lentinan alone and in combination with low dose of miltefosine against Leishmania donovani.

Lentinan exerts synergistic apoptotic effects with paclitaxel in A549 cells via activating ROS-TXNIP-NLRP3 inflammasome.

Paclitaxel is generally used to treat cancers in clinic as an inhibitor of cell division. However, the acquired resistance in tumours limits its clinical efficacy. Therefore, the aim of this study was to detect whether co-treatment with lentinan enhanced the anti-cancer effects of paclitaxel in A549 cells. We found that the combination of paclitaxel and lentinan resulted in a significantly stronger inhibition on A549 cell proliferation than paclitaxel treatment alone. Co-treatment with paclitaxel and lentinan enhanced cell apoptosis rate by inducing caspase-3 activation. Furthermore, co-treatment with paclitaxel and lentinan significantly triggered reactive oxygen species (ROS) production, and increased thioredoxin-interacting protein (TXNIP) expression. Moreover, co-treatment with paclitaxel and lentinan enhanced TXNIP-NLRP3 interaction, and activated NLRP3 inflammasome whereat interleukin-1ß levels were increased and cell apoptosis was induced. In addition, combination of paclitaxel and lentinan could activate apoptosis signal regulating kinase-1 (ASK1)/p38 mitogen-activated protein kinase (MAPK) signal which also contributed to cell apoptosis. Taken together, co-treatment with paclitaxel and lentinan exerts synergistic apoptotic effects in A549 cells through inducing ROS production, and activating NLRP3 inflammasome and ASK1/p38 MAPK signal pathway.