Exploring Adiponectin in Autosomal Dominant Kidney Disease: Insight and Implications.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common monogenic disorder characterized by renal cysts and progressive renal failure. In kidney diseases, adipose tissue undergoes functional changes that have been associated with increased inflammation and insulin resistance mediated by release of adipokines. Adiponectin is involved in various cellular processes, such as energy and inflammatory and oxidative processes. However, it remains to be determined whether adiponectin is involved in the concomitant metabolic dysfunctions present in PKD. In this scenario, we aimed to analyze: (a) PPARγ, ADIPOQ, ADIPOR1 and ADIPOR2 gene variations in 92 ADPKD patients through PCR-Sanger sequencing; and (b) adiponectin levels and its oligomerization state by ELISA and Western Blot. Our results indicated that: (a) 14 patients carried the PPARγ SNP, 29 patients carried the ADIPOQ SNP rs1501299, and 25 patients carried the analyzed ADIPOR1 SNPs. Finally, 82 patients carried ADIPOR2 SNPs; and (b) Adiponectin is statistically lower in ADPKD patients compared to controls, and further statistically lower in ESRD than in non-ESRD patients. An inverse relationship between adiponectin and albumin and between adiponectin and creatinine and a direct relationship between adiponectin and eGFR were found. Interestingly, significantly lower levels of adiponectin were found in patients bearing the ADIPOQ rs1501299 SNP and associated with low levels of eGFR. In conclusion, adiponectin levels and the presence of ADIPOQ rs1501299 genotype are significantly associated with a worse ADPKD phenotype, indicating that both could potentially provide important insights into the disease. Further studies are warranted to understand the pathophysiological role of adiponectin in ADPKD patients.

A Narrative Review on Adipose Tissue and Overtraining: Shedding Light on the Interplay among Adipokines, Exercise and Overtraining.

Lifestyle factors, particularly physical inactivity, are closely linked to the onset of numerous metabolic diseases. Adipose tissue (AT) has been extensively studied for various metabolic diseases such as obesity, type 2 diabetes, and immune system dysregulation due to its role in energy metabolism and regulation of inflammation. Physical activity is increasingly recognized as a powerful non-pharmacological tool for the treatment of various disorders, as it helps to improve metabolic, immune, and inflammatory functions. However, chronic excessive training has been associated with increased inflammatory markers and oxidative stress, so much so that excessive training overload, combined with inadequate recovery, can lead to the development of overtraining syndrome (OTS). OTS negatively impacts an athlete's performance capabilities and significantly affects both physical health and mental well-being. However, diagnosing OTS remains challenging as the contributing factors, signs/symptoms, and underlying maladaptive mechanisms are individualized, sport-specific, and unclear. Therefore, identifying potential biomarkers that could assist in preventing and/or diagnosing OTS is an important objective. In this review, we focus on the possibility that the endocrine functions of AT may have significant implications in the etiopathogenesis of OTS. During physical exercise, AT responds dynamically, undergoing remodeling of endocrine functions that influence the production of adipokines involved in regulating major energy and inflammatory processes. In this scenario, we will discuss exercise about its effects on AT activity and metabolism and its relevance to the prevention and/or development of OTS. Furthermore, we will highlight adipokines as potential markers for diagnosing OTS.

Exploring the neuroprotective activity of a lignanamides-rich extract in human neuroblastoma SH-SY5Y cells under dimethyl sulfoxide-induced stress.

Introduction: Dimethyl sulfoxide (DMSO) is widely used as a diluent and/or solvent for pharmacological compounds. Furthermore, DMSO crosses the blood-brain barrier acting on the nervous system. The natural compounds phenylamides and lignanamides (LnHS) have protective effects on neuronal health, being promising neuroprotective candidates. In this scenario, we evaluated the impact of DMSO and/or LnHS on SH-SY5Y and U-87 cells, taken as in vitro model of neurons and glia. Methods: Cells were treated with DMSO and/or LnHS at different doses and proliferation (MTT and trypan blue counting, colony forming ability, autophagy, oxidative stress (NO, ROS determination) and inflammatory (IL8, IL6, TNFα mRNA expression) response was evaluated. Results: We found that DMSO reduces both neuronal and glial cell viability, while LnHS does not affect viability of SH-SY5Y cells but reduces that of U-87 cells. Therefore, we focused on SHSY5Y cells and investigated whether LnHS could counteract DMSO toxicity. LnHS partially attenuates the inhibitory effects of DMSO on cell viability and restores the colony-forming ability of SH-SY5Y cells exposed to DMSO. Furthermore, we found that co-administration of LnHS modulates the expression of SIRT3 and SOD2 enzymes, reduces nitrite release and ROS generation increasing IL-8 levels. Interestingly, co-administration of LnHS counteracts the DMSO-induced production of IL-6, while no modification in TNF-α was found. Discussion: Our study indicates LnHS as a potential feasible compound to support neuronal health as it counteracts DMSO induced cytotoxic effects by improving SH-SY5Y cells survival. Further studies are needed to clarify the molecular mechanisms underlying the LnHS biological activities.

The Effects of Adiponectin on the Behavior of B-Cell Leukemia Cells: Insights from an In Vitro Study.

Background: Non-Hodgkin's lymphoma (NHL), the most frequent hematological neoplasm worldwide, represents a heterogeneous group of malignancies. The etiology of NHL remains to be fully elucidated, but the role of adipose tissue (AT) in immune function via the secretion of adipokines was recently recognized. Among adipokines, adiponectin has garnered attention for its beneficial properties. This study aimed to explore the in vitro effects of AdipoRon, an adiponectin agonist, on JVM-2, a lymphoblast cell line used as a representative disease model. Methods: JVM-2 cells were treated with different concentrations of AdipoRon to evaluate its effects on viability (via an MTT test), cell cycle distribution (via an FACS analysis), invasiveness (via a Matrigel assay) and colony-forming ability; protein expression was assessed via a real-time PCR (qPCR) and/or Western blotting (WB). Results: We found that the prolonged exposure of JVM-2 cells to AdipoRon led to a reduction in their viability due to a cytostatic effect. Additionally, AdipoRon stimulated both the formation of cell colonies and the expression of E-cadherin. Interestingly, the administration of AdipoRon increased the invasive potential of JVM-2 cells. Conclusions: Our findings indicate that adiponectin is involved in the regulation of different cellular processes of JVM-2 cells, supporting its potential association with a pro-tumorigenic phenotype and indicating that it might contribute to the increased aggressiveness and metastatic potential of B lymphoma cells. However, additional studies are required to fully understand the molecular mechanisms of adiponectin's actions on lymphoblasts and whether it may represent a marker of disease.

Adiponectin Alleviates Cell Injury due to Cerebrospinal Fluid from Multiple Sclerosis Patients by Inhibiting Oxidative Stress and Proinflammatory Response.

Multiple sclerosis (MS) is the most common disabling neurological disease characterized by chronic inflammation and neuronal cell viability impairment. Based on previous studies reporting that adiponectin exhibits neuroprotective effects in some models of neurodegenerative diseases, we analyzed the effects of AdipoRon treatment, alone or in combination with the cerebrospinal fluid of patients with MS (MS-CSF), to verify whether this adipokine acts on the basal neuronal cellular processes. To this aim, SH-SY5Y and U-87 cells (models of neuronal and glial cells, respectively) were exposed to MS-CSF alone or in co-treatment with AdipoRon. The cell viability was determined via MTT assay, and the possible underlying mechanisms were investigated via the alterations of oxidative stress and inflammation. MTT assay confirmed that AdipoRon alone did not affect the viability of both cell lines; whereas, when used in combination with MS-CSF, it reduces MS-CSF inhibitory effects on the viability of both SH-SY5Y and U-87 cell lines. In addition, MS-CSF treatment causes an increase in pro-inflammatory cytokines, whereas it determines the reduction in anti-inflammatory IL-10. Interestingly, the co-administration of AdipoRon counteracts the MS-CSF-induced production of pro-inflammatory cytokines, whereas it determines an enhancement of IL-10. In conclusion, our data suggest that AdipoRon counteracts the cytotoxic effects induced by MS-CSF on SH-SY5Y and U-87 cell lines and that one of the potential molecular underlying mechanisms might occur via reduction in oxidative stress and inflammation. Further in vivo and in vitro studies are essential to confirm whether adiponectin could be a neuro-protectant candidate against neuronal cell injury.

Improvement of adiponectin in relation to physical performance and body composition in young obese males subjected to twenty-four weeks of training programs.

Obesity and related metabolic diseases represent a worldwide health problem. The main factor predisposing to obesity is an unhealthy lifestyle including the lack of physical activity. A pivotal role in the etio-pathogenesis of obesity is carried out by adipose tissue, an endocrine organ secreting several adipokines involved in numerous metabolic and inflammatory processes. Among these, of particular importance is adiponectin, an adipokine involved in the regulation of insulin sensibility and in anti-inflammatory processes. The aim of the study was to determine the effects of 24 weeks of two different training programs polarized (POL) and threshold training (THR) on body composition, physical capacities and adiponectin expression. Thirteen male obese subjects (BMI: 32.0 ± 3.0 kg m-2) followed 24 weeks of two different training programs, POL and THR, consisting of walking or running (or a combination of the two methods) in their normal living conditions. Before (T0) and after the end of the program (T1), the assessment of body composition was assessed by bioelectrical impedance and the concentration of salivary and serum adiponectin was analyzed by enzyme-linked immunosorbent assay and western blotting. Although the results obtained did not show significant differences between the two training programs, body mass and body mass index decreased by a mean of -4.46 ± 2.90 kg and 1.43 ± 0.92 kg m-2 (P < 0.05). Fat mass decreased by -4.47 ± 2.78 kg (P < 0.05). V'O2max increased by a mean of 0.20 ± 0.26 L min-1 (P < 0.05) Also, we observed an increase in saliva and in serum of adiponectin concentrations at T1 compared to T0 by 4.72 ± 3.52 µg mL-1 and 5.22 ± 4.74 ng mL-1 (P < 0.05) respectively. Finally, we found significant correlations between Δ serum adiponectin and Δ Hip (R = -0.686, P = 0.001) and between Δ salivary adiponectin and ΔWaist (R = -0.678, P = 0.011). Our results suggest that a 24 weeks training program, independently from intensity and volume, induces an amelioration of body composition and fitness performance. These improvements are associated with an increase in total and HMW adiponectin expression in both saliva and in serum.

Adiponectin Increase in Patients Affected by Chronic Obstructive Pulmonary Disease with Overlap of Bronchiectasis.

Chronic obstructive pulmonary disease (COPD) is characterized by respiratory symptoms and non-reversible airflow limitation with recurrent episodes of acute exacerbations. The concurrent presence of bronchiectasis in patients with COPD is associated with reduced respiratory function as well as increased exacerbation risk. Adiponectin is a promising biomarker in COPD, as greater high molecular weight (HMW) oligomer levels have been observed among COPD patients. Here, we investigate adiponectin levels in two groups of COPD patients characterized by the presence or absence of bronchiectasis (BCO), comparing both groups to healthy controls. We evaluated serum adiponectin levels in COPD patients, those with BCO, and healthy subjects and characterized the pattern of circulating adiponectin oligomers. We found that forced volume capacity % (FVC%) and forced expiratory volume % (FEV1%) were lower for BCO patients than for COPD patients. COPD patients had higher levels of adiponectin and its HMW oligomers than healthy controls. Interestingly, BCO patients had higher levels of adiponectin than COPD patients. We showed that expression levels of IL-2, -4, and -8, IFN-γ, and GM-CSF were significantly higher in BCO patients than in healthy controls. Conversely, IL-10 expression levels were lower in BCO patients. Our data suggest that the increased levels of adiponectin detected in the cohort of BCO patients compared to those in COPD patients without bronchiectasis might be determined by their worse airway inflammatory state. This hypothesis suggests that adiponectin could be considered as a biomarker to recognize advanced COPD patients with bronchiectasis.

Adiponectin, Leptin, and Resistin Are Dysregulated in Patients Infected by SARS-CoV-2.

Obesity, through adipose tissue (AT) inflammation and dysregulation, represents a critical factor for COVID-19; here, we investigated whether serum levels of adiponectin, HMW oligomers, leptin, and resistin are modulated and/or correlated with clinical and biochemical parameters of severe COVID-19 patients. This study included 62 severe COVID-19 patients; 62 age and sex-matched healthy subjects were recruited as a control group. Anthropometric and biochemical parameters were obtained and compared. Adiponectin, HMW oligomers, leptin, and resistin were analyzed by ELISA. The adiponectin oligomerization state was visualized by Western blotting. When compared to healthy subjects, total adiponectin levels were statistically lower in severe COVID-19 while, in contrast, the levels of leptin and resistin were statistically higher. Interestingly, HMW adiponectin oligomers negatively correlated with leptin and were positively associated with LUS scores. Resistin showed a positive association with IL-6, IL-2R, and KL-6. Our data strongly support that adipose tissue might play a functional role in COVID-19. Although it needs to be confirmed in larger cohorts, adiponectin HMW oligomers might represent a laboratory resource to predict patient seriousness. Whether adipokines can be integrated as a potential additional tool in the evolving landscape of biomarkers for the COVID-19 disease is still a matter of debate. Other studies are needed to understand the molecular mechanisms behind adipokine's involvement in COVID-19.

Circulating microRNAs in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a pathology characterized by chronic inflammation and skin lesions. The molecular basis of the inflammatory network remains unclear; however, since microRNAs (miRNAs) are involved in the modulation of inflammation, the composition of a micro-transcriptome RNA library using the blood of HS patients was analysed here. The total miRNA expression profiles of miRNAs from HS patients was assayed by real-time qPCR. Here, compared to healthy controls, miR-24-1-5p, miR-146a-5p, miR26a-5p, miR-206, miR338-3p, and miR-338-5p expression was found significantly different in HS. Knowing the significance of the miRNA mechanism in inflammatory and immune progression, we suggest that miRNA profiles found in HS patients can be significant in understanding the pathogenesis modality and establishing efficient biomarkers for HS early diagnosis. In particular, miR-338-5p was closely related to HS invasiveness and production of cytokines and was atypically overexpressed. miR-338-5p may represent a good promise as a non-invasive clinical biomarker for HS.

Cannabidiolic acid in Hemp Seed Oil Table Spoon and Beyond.

Cannabidiolic acid (CBDA) is the main precannabinoid in industrial hemp. It represents a common constituent of hemp seed oil, but mainly abundant in the aerial parts of the plant (including their processing waste). Thus, the optimization of fast and low-cost purification strategies is mandatory, as well as a deep investigation on its nutraceutical and cosmeceutical properties. To this purpose, CBDA content in hemp seed oil is evaluated, and its recovery from wasted leaves is favorably achieved. The cytotoxicity screening towards HaCaT cells, by means of MTT, SRB and LDH release assays, suggested it was not able to decrease cell viability or perturb cell integrity up to 10 µM concentration. Thus, the ability of CBDA to differentially modulate the release of proinflammatory cytokines and chemokines mediators has been evaluated, finding that CBDA decreased IFN-γ, CXCL8, CXCL10, CCL2, CCL4 and CCL5, mostly in a dose-dependent manner, with 10 µM tested concentration exerting the highest activity. These data, together with those from assessing antimicrobial activity against Gram(+) and Gram(-) bacteria and the antibiofilm formation, suggest that CBDA is able to counteract the inflammatory response, also preventing bacteria colonization.

GDM-complicated pregnancies: focus on adipokines.

Gestational diabetes mellitus (GDM) is a serious complication of pregnancy and is defined as a state of glucose intolerance that is first diagnosed and arises during gestation. Although the pathophysiology of GDM has not yet been thoroughly clarified, insulin resistance and pancreatic ß-cell dysfunction are considered critical components of its etiopathogenesis. To sustain fetus growth and guarantee mother health, many significant changes in maternal metabolism are required in normal and high-risk pregnancy accompanied by potential complications. Adipokines, adipose tissue-derived hormones, are proteins with pleiotropic functions including a strong metabolic influence in physiological conditions and during pregnancy too. A growing number of studies suggest that various adipokines including adiponectin, leptin, visfatin, resistin and tumor necrosis factor α (TNF-α) are dysregulated in GDM and might have pathological significance and a prognostic value in this pregnancy disorder. In this review, we will focus on the current knowledge on the role that the aforementioned adipokines play in the development and progression of GDM.

AdipoRon negatively regulates proliferation and migration of ARPE-19 human retinal pigment epithelial cells.

Adiponectin is an adipokine playing important roles in metabolic, inflammatory and proliferative processes. At the time of surgery for rhegmatogenous retinal detachment, an altered expression of adipokines has been associated with the development of future proliferative vitreoretinopathy (PVR); this evidence as well as the presence of adiponectin receptors in ocular tissues and cell lines suggests a role of adiponectin in the physio-pathology of ocular conditions. Here, we investigated the effects of AdipoRon, an adiponectin agonist, on ARPE-19, a human retinal pigment epithelial cell line after confirming the expression of AdipoR1, AdipoR2, T-cadherin receptors. We evaluated the effects of AdipoRon in terms of vitality, survival, and migration; furthermore, we investigated the potential effects of AdipoRon on the inflammatory state of ARPE-19 cells analysing the levels of IL-10, VEGF, MCP-1 and IL-6 cytokines. Our findings indicated that AdipoRon, in a time and dose-dependent manner, reduces cell proliferation, migration, and colony formation of ARPE-19 cells. On the contrary, AdipoRon administration does not affect the expression of the tested cytokines. In conclusion, our results indicated that AdipoRon, may constitute an endogenous inhibitor of retinal pigment epithelial cell proliferation and migration, both processes deeply involved in development of PVR. Since PVR are characterized by an aberrant growth, migration and dedifferentiation of retinal pigment epithelial cells, our data contribute to open new fields of research to develop innovative therapeutic targets. Further studies are needed to clarify the effects of AdipoRon and of other small-molecule adiponectin analogs on retinal epithelium to clarify the functional role of adiponectin.

Adiponectin and Leptin Exert Antagonizing Effects on HUVEC Tube Formation and Migration Modulating the Expression of CXCL1, VEGF, MMP-2 and MMP-9.

Adiponectin and leptin are two abundant adipokines with different properties but both described such as potent factors regulating angiogenesis. AdipoRon is a small-molecule that, binding to AdipoRs receptors, acts as an adiponectin agonist. Here, we investigated the effects of AdipoRon and leptin on viability, migration and tube formation on a human in vitro model, the human umbilical vein endothelial cells (HUVEC) focusing on the expression of the main endothelial angiogenic factors: hypoxia-inducible factor 1-alpha (HIF-1α), C-X-C motif chemokine ligand 1 (CXCL1), vascular endothelial growth factor A (VEGF-A), matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9). Treatments with VEGF-A were used as positive control. Our data revealed that, at 24 h treatment, proliferation of HUVEC endothelial cells was not influenced by AdipoRon or leptin administration; after 48 h longer exposure time, the viability was negatively influenced by AdipoRon while leptin treatment and the combination of AdipoRon+leptin produced no effects. In addition, AdipoRon induced a significant increase in complete tubular structures together with induction of cell migration while, on the contrary, leptin did not induce tube formation and inhibited cell migration; interestingly, the co-treatment with both AdipoRon and leptin determined a significant decrease of the tubular structures and cell migration indicating that leptin antagonizes AdipoRon effects. Finally, we found that the effects induced by AdipoRon administration are accompanied by an increase in the expression of CXCL1, VEGF-A, MMP-2 and MMP-9. In conclusion, our data sustain the active role of adiponectin and leptin in linking adipose tissue with the vascular endothelium encouraging the further deepening of the role of adipokines in new vessel's formation, to candidate them as therapeutic targets.

Food, Nutrition, Physical Activity and Microbiota: Which Impact on Lung Cancer?

Lung cancer still represents the leading cause of cancer-related death, globally. Likewise, malnutrition and inactivity represent a major risk for loss of functional pulmonary capacities influencing overall lung cancer severity. Therefore, the adhesion to an appropriate health lifestyle is crucial in the management of lung cancer patients despite the subtype of cancer. This review aims to summarize the available knowledge about dietary approaches as well as physical activity as the major factors that decrease the risk towards lung cancer, and improve the response to therapies. We discuss the most significant dietary schemes positively associated to body composition and prognosis of lung cancer and the main molecular processes regulated by specific diet schemes, functional foods and physical activity, i.e., inflammation and oxidative stress. Finally, we report evidence demonstrating that dysbiosis of lung and/or gut microbiome, as well as their interconnection (the gut-lung axis), are strictly related to dietary patterns and regular physical activity playing a key role in lung cancer formation and progression, opening to the avenue of modulating the microbiome as coadjuvant therapy. Altogether, the evidence reported in this review highlights the necessity to consider non-pharmacological interventions (nutrition and physical activity) as effective adjunctive strategies in the management of lung cancer.

Adiponectin and leptin exert antagonizing effects on proliferation and motility of papillary thyroid cancer cell lines.

Adiponectin (Acrp30) and leptin, adipokines produced and secreted mainly by the adipose tissue, are involved in human carcinogenesis. Thyroid carcinomas are frequent endocrine cancers, and several evidences suggest that they are correlated with obesity. In this study, we first analyzed the expression levels and prognostic values of Acrp30, leptin, and their receptors in thyroid cancer cells. Then, we investigated the role of Acrp30 and leptin in proliferation, migration, and invasion. We found that Acrp30 treatment alone inhibits cell proliferation and cell viability in a time and dose-dependent manner; leptin alone does not influence thyroid cancer cells (BCPAP and K1) proliferation, but the combined treatment reverts Acrp30-induced effects on cell proliferation. Additionally, through wound healing and Matrigel Matrix invasion assays, we unveiled that Acrp30 inhibits thyroid cancer cell motility, while leptin induces the opposite effect. Importantly, in the combined treatment, Acrp30 and leptin exert antagonizing effects on papillary thyroid cancer cells' migration and invasion in both BCPAP and K1 cell lines. Highlights of these studies suggest that Acrp30 and leptin could represent therapeutic targets and biomarkers for the management of thyroid cancer.

Adiponectin in Cerebrospinal Fluid from Patients Affected by Multiple Sclerosis Is Correlated with the Progression and Severity of Disease.

Adiponectin exerts relevant actions in immunity and is modulated in several disorders, such as multiple sclerosis (MS). In this study, we characterized adiponectin expression and profiles in cerebrospinal fluid (CSF) from MS patients to investigate its potential relationship with the severity and progression of the disease. Total adiponectin in CSF was measured by ELISA in 66 unrelated CSF MS patients and compared with 24 age- and sex-matched controls. Adiponectin oligomer profiles were analysed by Western blotting and FPLC chromatography. Total CSF adiponectin was significantly increased in MS patients compared with controls (9.91 ng/mL vs 6.02 ng/mL) (p < 0.001). Interestingly, CSF adiponectin positively correlated with CSF IgG, and CSF/serum albumin directly correlated with CSF/serum adiponectin. Our data demonstrated that CSF adiponectin predicts a worse prognosis: patients with the progressive form of MS had higher levels compared with the relapsing remitting form; patients with higher EDSS at baseline and a higher MS severity score at 4.5-year follow-up had significantly elevated adiponectin levels with respect to patients with a less severe phenotype. Finally, the adiponectin oligomerization profile was altered in CSF from MS patients, with a significant increase in HMW and MMW. The correlation of CSF adiponectin with the severity and prognosis of MS disease confirmed the role of this adipokine in the inflammatory/immune processes of MS and suggested its use as a complementary tool to assess the severity, progression and prognosis of the disease. Further studies on larger MS cohorts are needed to clarify the contribution of adiponectin to the etiopathogenesis of MS.

Hempseed Lignanamides Rich-Fraction: Chemical Investigation and Cytotoxicity towards U-87 Glioblastoma Cells.

The weak but noteworthy presence of (poly)phenols in hemp seeds has been long overshadowed by the essential polyunsaturated fatty acids and digestible proteins, considered responsible for their high nutritional benefits. Instead, lignanamides and their biosynthetic precursors, phenylamides, seem to display interesting and diverse biological activities only partially clarified in the last decades. Herein, negative mode HR-MS/MS techniques were applied to the chemical investigation of a (poly)phenol-rich fraction, obtained from hemp seeds after extraction/fractionation steps. This extract contained phenylpropanoid amides and their random oxidative coupling derivatives, lignanamides, which were the most abundant compounds and showed a high chemical diversity, deeply unraveled through high resolution tandem mass spectrometry (HR-MS/MS) tools. The effect of different doses of the lignanamides-rich extract (LnHS) on U-87 glioblastoma cell line and non-tumorigenic human fibroblasts was evaluated. Thus, cell proliferation, genomic DNA damage, colony forming and wound repair capabilities were assessed, as well as LnHS outcome on the expression levels of pro-inflammatory cytokines. LnHS significantly inhibited U-87 cancer cell proliferation, but not that of fibroblasts, and was able to reduce U-87 cell migration, inducing further DNA damage. No modification in cytokines' expression level was found. Data acquired suggested that LnHS acted in U-87 cells by inducing the apoptosis machinery and suppressing the autophagic cell death.