α-Solanine attenuates chondrocyte pyroptosis to improve osteoarthritis via suppressing NF-κB pathway.

α-Solanine has been shown to exhibit anti-inflammatory and anti-tumour properties; however, its efficacy in treating osteoarthritis (OA) remains ambiguous. The study aimed to evaluate the therapeutic effects of α-solanine on OA development in a mouse OA model. The OA mice were subjected to varying concentrations of α-solanine, and various assessments were implemented to assess OA progression. We found that α-solanine significantly reduced osteophyte formation, subchondral sclerosis and OARSI score. And it decreased proteoglycan loss and calcification in articular cartilage. Specifically, α-solanine inhibited extracellular matrix degradation by downregulating collagen 10, matrix metalloproteinase 3 and 13, and upregulating collagen 2. Importantly, α-solanine reversed chondrocyte pyroptosis phenotype in articular cartilage of OA mice by inhibiting the elevated expressions of Caspase-1, Gsdmd and IL-1ß, while also mitigating aberrant angiogenesis and sensory innervation in subchondral bone. Mechanistically, α-solanine notably hindered the early stages of OA progression by reducing I-κB phosphorylation and nuclear translocation of p65, thereby inactivating NF-κB signalling. Our findings demonstrate the capability of α-solanine to disrupt chondrocyte pyroptosis and sensory innervation, thereby improving osteoarthritic pathological progress by inhibiting NF-κB signalling. These results suggest that α-solanine could serve as a promising therapeutic agent for OA treatment.

Solanine induces ferroptosis in colorectal cancer cells through ALOX12B/ADCY4 molecular axis.

OBJECTIVES: Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer worldwide. Solanine is a phytochemical extracted from traditional Chinese medicine with widely reported anticancer effects. Here, we investigated the potential role of solanine in regulating ferroptosis in CRC cells and scrutinized the molecular mechanism. METHODS: Cell growth and cytotoxicity were examined using CCK-8 proliferation assay and lactate dehydrogenase assay. Oxidative stress was determined by measuring glutathione (GSH), malondialdehyde, and reactive oxygen species (ROS) levels. Subcellular changes in mitochondria were examined by transmission electron microscopy. Gene and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein-protein interaction was determined by co-immunoprecipitation. KEY FINDINGS: Solanine arrested cell proliferation in CRC cells and induced typical ferroptotic changes. Solanine treatment promoted ROS production, lipid peroxidation, and cell membrane disruption, while the cellular level of antioxidant GSH was reduced upon solanine treatment. ALOX12B was identified as a molecular mediator of solanine to promote ferroptosis. Solanine treatment upregulated ALOX12B levels and silencing ALOX12B could suppress solanine-induced ferroptosis. Further, ADCY4 was found to physically associate with ALOX12B and maintain ALOX12B protein stability. Silencing ADCY4 destabilized ALOX12B and attenuated solanine-induced ferroptosis. CONCLUSIONS: Our data demonstrated the ferroptosis-inducing effect of solanine in CRC cells, and revealed ALOX12B/ADCY4 molecular axis as the ferroptosis mediator of solanine. Solanine may synergize with existing ferroptosis inducer as an anticancer strategy in CRC, which warrants further validation in animal experiments.

Antioxidants Amelioration Is Insufficient to Prevent Acrylamide and Alpha-Solanine Synergistic Toxicity in BEAS-2B Cells.

Cells produce free radicals and antioxidants when exposed to toxic compounds during cellular metabolism. However, free radicals are deleterious to lipids, proteins, and nucleic acids. Antioxidants neutralize and eliminate free radicals from cells, preventing cell damage. Therefore, the study aims to determine whether the antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) will ameliorate the maximum dose of acrylamide and alpha (α)-solanine synergistic toxic effects in exposed BEAS-2B cells. These toxic compounds are consumed worldwide by eating potato products. BEAS-2B cells were simultaneously treated with BHA 10 µM and BHT 20 µM and incubated in a 5% CO2 humidified incubator for 24 h, followed by individual or combined treatment with acrylamide (3.5 mM) and α-solanine (44 mM) for 48 h, including the controls. Cell morphology, DNA, RNA, and protein were analyzed. The antioxidants did not prevent acrylamide and α-solanine synergistic effects in exposed BEAS-2B cells. However, cell morphology was altered; polymerase chain reaction (PCR) showed reduced RNA constituents but not DNA. In addition, the toxic compounds synergistically inhibited AKT/PKB expression and its downstream genes. The study showed BHA and BHT are not protective against the synergetic toxic effects of acrylamide and α-solanine in exposed BEAS-2B cells.

Alkalihalobacillus clausii PA21 transcriptome profiling and functional analysis revealed the metabolic pathway involved in glycoalkaloids degradation.

Glycoalkaloids (GAs), including α-solanine and α-chaconine, are secondary metabolites found in potato, which are toxic to higher animals. In a previous study, Alkalihalobacillus clausii PA21 showed the capacity to degrade GAs. Herein, the transcriptome response of PA21 to α-solanine or α-chaconine was evaluated. In total, 3170 and 2783 differential expressed genes (DEGs) were found in α-solanine- and α-chaconine-treated groups, respectively, with most DEGs upregulated. Moreover, GAs activated transmembrane transport, carbohydrate metabolism, transcription, quorum sensing, and bacterial chemotaxis in PA21 to withstand GA-induced stress and promote GAs degradation. Furthermore, qRT-PCR analysis confirmed the upregulation of degrading enzymes and components involved in GA degradation in PA21. In addition, the GAs-degrading enzymes were heterologous expressed, purified, and incubated with GAs to analyze the degradation products. The results showed that α-solanine was degraded to ß1-solanine, ß2-solanine, γ-solanine, and solanidine by ß-glucosidase, α-rhamnosidase, and ß-galactosidase. Meanwhile, α-chaconine was degraded to ß1-chaconine, ß2-chaconine, γ-chaconine, and solanidine by ß-glucosidase and α-rhamnosidase. Overall, the molecular mechanism underlying GAs degradation by PA21 was revealed by RNAseq combined with protein expression and function studies, thus providing the basis for the development of engineered bacteria that can efficiently degrade GAs to promote their application in the control of GAs in potatoes.

Solanine Represses Gastric Cancer Growth by Mediating Autophagy Through AAMDC/MYC/ATF4/Sesn2 Signaling Pathway.

Purpose: Solanine is the main component of the plant Solanum, which has been shown to provide growth-limiting activities in a variety of human cancers. However, little is known about its function in gastric cancer (GC). Methods: We investigated the effect of solanine on GC in vivo and in vitro. The inhibition rate of solanine on the tumor was observed by constructing a subcutaneous tumor in nude mice. Morphological changes were analyzed with H&E staining. The expression of ATF4 was detected by IF analysis. MTT assays, EdU staining, and colony formation assays were used to detect the inhibition rate of solanine on GC cells. Matrigel transwells were used to detect the invasion of GC cells. Cell migration was measured using the wound healing assay. The flow cytometric analysis was used to monitor changes in the cell cycle and cell apoptosis. Western blotting was used to detect major proteins in cells and tumors. Results: Solanine suppressed gastric tumorigenesis. Solanine also inhibited the proliferation, invasion and mitigation of GC cells, and induced cell cycle arrest and apoptosis in vitro. Moreover, the growth-limiting activities of solanine in gastric cancer were related to the suppression of the AAMDC/MYC/ATF4/Sesn2 pathway-mediated autophagy. Overexpression of AAMDC reversed the inhibitory effect of solanine on autophagy and gastric cancer. Conclusion: In summary, our findings indicate that solanine confers growth-limiting activities by deactivating the AAMDC-regulated autophagy in gastric cancer.

Anti-Cancer Role of Dendrosomal Nano Solanine in Chronic Myelogenous Leukemia Cell Line through Attenuation of PI3K/AKT/mTOR Signaling Pathway and Inhibition of hTERT Expression.

BACKGROUND: Solanine was primarily known as a toxic compound. Nonetheless, recently the apoptotic role of solanine through suppression of PI3K/AKT/mTOR signaling pathway has been shown against many malignancies except chronic myelogenous leukemia (CML). Sustaining the aforementioned pro-survival pathway, BCR-ABL fused oncoprotein in CML activates NF-kB and c- MYC for apparent immortalizing factor hTERT. Since solanine is a poor water-soluble molecule, herein, a nanocarrier was employed to intensify its pernicious effect on cancerous cells. OBJECTIVE: The current research aimed at evaluating the effect of dendrosomal nano solanine (DNS) on leukemic and HUVEC cells. METHODS: DNS characterization was determined by NMR, DLS and TEM. The viability, apoptosis and cell cycle of DNS and imatinib-treated cells were determined. A quantitative real-time PCR was employed to measure the expression of PI3K, AKT, mTOR, S6K, NF-kB, c-MYC and hTERT mRNAs. The Protein levels were evaluated by western blot. RESULTS: Investigating the anticancer property of free and dendrosomal nano solanine (DNS) and the feasible interplaying between DNS and imatinib on leukemic cells, we figured out the potential inhibitory role of DNS and DNS+IM on cancerous cells in comparison with chemotherapy drugs. Moreover, results revealed that the encapsulated form of solanine was much more preventive on the expression of PI3KCA, mTOR, NF-kB, c-MYC and hTERT accompanied by the dephosphorelating AKT protein. CONCLUSION: The results advocate the hypothesis that DNS, rather than solanine, probably due to impressive penetration, can restrain the principal pro-survival signaling pathway in erythroleukemia K562 and the HL60 cell lines and subsequently declined mRNA level of hTERT which causes drug resistance during long-term treatment. Additionally, combinational treatment of DNS and IM could also bestow an additive anti-leukemic effect. As further clinical studies are necessary to validate DNS efficacy on CML patients, DNS could have the potency to be considered as a new therapeutic agent even in combination with IM.

Quantitation of Toxic Steroidal Glycoalkaloids and Newly Identified Saponins in Post-Harvest Light-Stressed Potato (Solanum tuberosum L.) Varieties.

Although domesticated potatoes contain a large variety of steroidal glycoalkaloids (SGAs) and saponins, in the past, many research projects mainly focused on the two major SGAs, α-solanine and α-chaconine. This study investigates the quantitative changes, induced by post-harvest LED light exposure, of six SGAs and four saponins in 12 potato cultivars at three different time points (1, 7, and 16 days), by using ultra-performance liquid chromatography tandem mass spectrometry. Altogether, SGA contents of 3.0-17.1 mg/100 g fresh weight (FW) could be observed in the analyzed tubers with potato varieties highly exceeding the newly discussed safety limit of 10 mg/100 g. The overall contents of 0.1-5.4 mg/100 g FW of the so far barely studied saponins, like protoneodioscin or barogenin-solatrioside, highly differed between the assayed potato cultivars. Furthermore, cultivar-specific regulations of SGAs and saponins could be observed due to light exposure.

Solanaceae glycoalkaloids: α-solanine and α-chaconine modify the cardioinhibitory activity of verapamil.

CONTEXT: Solanaceae glycoalkaloids (SGAs) possess cardiomodulatory activity. OBJECTIVE: This study investigated the potential interaction between verapamil and glycoalkaloids. MATERIAL AND METHODS: The cardioactivity of verapamil and glycoalkaloids (α-solanine and α-chaconine) was tested in adult beetle (Tenebrio molitor) myocardium in vitro using microdensitometric methods. The myocardium was treated with pure substances and mixtures of verapamil and glycoalkaloids for 9 min with saline as a control. Two experimental variants were used: simultaneous application of verapamil and glycoalkaloids or preincubation of the myocardium with one of the compounds followed by perfusion with a verapamil solution. We used 9 × 10-6-5 × 10-5 M and 10-9-10-5 M concentration for verapamil and glycoalkaloids, respectively. RESULTS: Verapamil, α-solanine and α-chaconine showed cardioinhibitory activity with IC50 values equal to 1.69 × 10-5, 1.88 × 10-7 and 7.48 × 10-7 M, respectively. When the glycoalkaloids were applied simultaneously with verapamil, an antagonistic effect was observed with a decrease in the maximal inhibitory effect and prolongation of t50 and the recovery time characteristic of verapamil. We also confirmed the expression of two transcript forms of the gene that encodes the α1 subunit of L-type calcium channels in the myocardium and brain with equal transcription levels of both forms in the myocardium and significant domination of the shorter form in the brain of the insect species tested. DISCUSSION AND CONCLUSIONS: The results show that attention to the composition of the daily diet during therapy with various drugs is particularly important. In subsequent studies, the nature of interaction between verapamil and SGAs on the molecular level should be checked, and whether this interaction decreases the efficiency of cardiovascular therapy with verapamil in humans.

Alpha-solanine Anti-tumor Effects in Non-small Cell Lung Cancer Through Regulating the Energy Metabolism Pathway.

BACKGROUND: Lung cancer is a malignant tumor with a high incidence in China, especially non-small cell lung cancer (NSCLC), which is the main threat to human life, with terrible morbidity and mortality. The research on the treatment and mechanism of NSCLC has been the forefront and hotspot of research. Recent patents show that alpha-solanine (α-solanine) exhibits the best anti-cancer activity, although its target and related mechanism remain to be elucidated. OBJECTIVES: This study aims to explore the possible targets and mechanisms of α-solanine in the treatment of NSCLC through network pharmacology and experimental verification. METHODS: Network pharmacology was applied to screen the possible targets of α-solanine on NSCLC, construct core networks, and perform GO enrichment and KEGG pathway analysis to predict the mechanism of α-solanine against NSCLC. Experiments were implemented to verify the results of network pharmacology in vitro. The A549 and PC-9 cells were exposed to α-solanine to assess the anti-tumor effect. Cell apoptosis was determined by the Annexin-V/PI assay. Targeted energy metabolomics was used to validate the network pharmacology results, and energy metabolism pathway- related proteins were detected by immunofluorescence and western blot. RESULTS: Network pharmacology showed that there were 130 potential targets of α-solanine and NSCLC. GO, and KEGG analysis showed that the energy metabolism pathway is the main pathway for α-solanine to exert anti-tumor effects on NSCLC. Experimental results showed that α-solanine inhibited cell proliferation, migration, invasion and promoted cell apoptosis. At the same time, after α-solanine treatment, the energy metabolism pathway-related proteins, including GPI, ALDOA, TPI1, PKLR, LDHA, and ALDH3, were expressed reduced. In addition, α-solanine also affects the amino acid metabolism of A549 and PC-9 cells. CONCLUSION: Based on a combination of network pharmacological prediction and experimental verification, α-solanine may exert anti-NSCLC effects by regulating the energy metabolism pathway.

Bioactive Substances of Potato Juice Reveal Synergy in Cytotoxic Activity against Cancer Cells of Digestive System Studied In Vitro.

More and more literature data indicate the health-promoting effect of potato juice (PJ). However, to date, it has not been precisely explained which of the many compounds present in PJ exhibit biological activity. The work aimed to establish the antiproliferative effect of gastrointestinal digested PJ and the products of its processing. Fresh PJs derived from three edible potato varieties, industrial side stream resulting from starch production, partially deproteinized PJ derived from feed protein production line, and three different potato protein preparations subjected to digestion in the artificial gastrointestinal tract were used in this study. The cytotoxic potential of glycoalkaloids (GAs), phenolic acids, digested PJ, and products of PJ processing was determined in human normal and cancer cells derived from the digestive system. The results showed that GAs exhibit concentration-dependent cytotoxicity against all analyzed cell lines. In contrast, phenolic acids (caffeic, ferulic, and chlorogenic acid) do not show cytotoxicity in the applied cell lines. A correlation between cytotoxic potency and GAs content was found in all PJ products studied. The most potent effects were observed under treatment with deproteinized PJ, a product of industrial processing of PJ, distinguished by the highest effective activity among the fresh juice products studied. Moreover, this preparation revealed a favorable cytotoxicity ratio towards cancer cells compared to normal cells. Statistical analysis of the obtained results showed the synergistic effect of other bioactive substances contained in PJ and its products, which may be crucial in further research on the possibility of using PJ as a source of compounds of therapeutic importance.

Selective extraction and determination of steroidal glycoalkaloids in potato tissues by electromembrane extraction combined with LC-MS/MS.

For the first time, electromembrane extraction (EME) combined LC-MS/MS was applied to extract and determine α-solanine and α-chaconine in different potato tissues using NPOE containing 20% (v/v) DEHP as supported liquid membrane (SLM). Under the optimal conditions, the proposed EME-LC-MS/MS method was evaluated using spiked fresh potato peel sample. The linear range for α-solanine and α-chaconine was 5-1000 ng mL-1 (R2 > 0.9991), with LOD and LOQ of 1.2-1.5 ng mL-1 and 4.1-5.2 ng mL-1, respectively. Repeatability for α-solanine and α-chaconine at three concentration levels was satisfactory (<4.9%), and recoveries ranged from 73% to 106%. Finally, the EME-LC-MS/MS method has been successfully employed to determine α-solanine and α-chaconine in sprouted potato peel and tuber samples, indicating that EME exhibited high selectivity and efficient sample clean-up capability. Consequently, EME showed great potential for extraction and purification of toxic and bioactive basic compounds from complex plant tissues.

Involvement of miRNAs in response to oxidative stress induced by the steroidal glycoalkaloid α-solanine in hepatocellular carcinoma cells.

BACKGROUND: α-Solanine is a natural toxic glycoalkaloid produced in some species of the Solanaceae family with antiproliferative activity in various cancers. OBJECTIVE: This study aimed to investigate the effect of α-solanine on the oxidative stress status in human hepatocellular carcinoma HepG2 cells and to evaluate its influence on microRNAs (miRNAs) associated with oxidative stress and NF-κB regulation. METHODS: The prooxidant effect of α-solanine was tested by the decay rate of the fluorescent probe, ß-phycoerythrin, and by measuring malondialdehyde, reduced Glutathione, catalase, and superoxide dismutase following treatment of HepG2 cells with low doses of α-solanine. Immunocytochemical techniques were used to detect mitochondrial membrane potential (ΔΨm) and NF-κB protein. The gene expression of NF-κB and miRNAs was evaluated by real-time PCR. RESULTS: α-Solanine is a prooxidant that causes a rapid decay in the fluorescence intensity of ß-phycoerythrin. It induces oxidative stress-related alterations such as increased lipid peroxidation and reduced antioxidant markers. Oxidative stress induced by α-solanine was mediated by decreased ΔΨm, increased NF-κB expression, upregulation of miRNAs that control oxidative stress by regulating the NF-κB pathway, and downregulation of oncogenic miRNAs that inhibit the NF-κB pathway. CONCLUSION: α-Solanine-induced oxidative stress is mediated by alterations in the NF-κB pathway with a detected crosstalk between α-solanine treatment and the expression of oxidative stress-responsive miRNAs.

Maleic and L-tartaric acids as new anti-sprouting agents for potatoes during storage in comparison to other efficient sprout suppressants.

Inhibiting sprouting of potatoes is an interesting subject needed for potato storage and industry. Sprouting degrades the quality of tuber along with releasing α-solanine and α-chaconine, which are harmful for health. Sprout suppressants, available in the market, are either costly or toxic to both health and environment. So, there is a need for developing countries to explore new sprouting suppressant compound which is cheap, non-toxic and reasonably efficient in comparison to commercial ones. We have established that simple maleic acid and L-tartaric acid are effective sprout suppressing agents. Both can hinder sprouting up to 6 weeks and 4 weeks post treatment respectively at room temperature in dark. These do not affect the quality parameters, retain the moisture content and maintain the stout appearance of the tubers along the total storage period. Thus maleic acid and L-tartaric acid would qualify as alternative, cheap, efficient sprout suppressant for potato storage and processing.

Characterization of C-26 aminotransferase, indispensable for steroidal glycoalkaloid biosynthesis.

Steroidal glycoalkaloids (SGAs) are toxic specialized metabolites found in members of the Solanaceae, such as Solanum tuberosum (potato) and Solanum lycopersicum (tomato). The major potato SGAs are α-solanine and α-chaconine, which are biosynthesized from cholesterol. Previously, we have characterized two cytochrome P450 monooxygenases and a 2-oxoglutarate-dependent dioxygenase that function in hydroxylation at the C-22, C-26 and C-16α positions, but the aminotransferase responsible for the introduction of a nitrogen moiety into the steroidal skeleton remains uncharacterized. Here, we show that PGA4 encoding a putative γ-aminobutyrate aminotransferase is involved in SGA biosynthesis in potatoes. The PGA4 transcript was expressed at high levels in tuber sprouts, in which SGAs are abundant. Silencing the PGA4 gene decreased potato SGA levels and instead caused the accumulation of furostanol saponins. Analysis of the tomato PGA4 ortholog, GAME12, essentially provided the same results. Recombinant PGA4 protein exhibited catalysis of transamination at the C-26 position of 22-hydroxy-26-oxocholesterol using γ-aminobutyric acid as an amino donor. Solanum stipuloideum (PI 498120), a tuber-bearing wild potato species lacking SGA, was found to have a defective PGA4 gene expressing the truncated transcripts, and transformation of PI 498120 with functional PGA4 resulted in the complementation of SGA production. These findings indicate that PGA4 is a key enzyme for transamination in SGA biosynthesis. The disruption of PGA4 function by genome editing will be a viable approach for accumulating valuable steroidal saponins in SGA-free potatoes.

Biosynthesis of α-solanine and α-chaconine in potato leaves (Solanum tuberosum L.) - A 13CO2 study.

α-Solanine and α-chaconine are the major glycoalkaloids (SGAs) in potatoes, but up to now the biosynthesis of these saponins is not fully understood. In planta13CO2 labeling experiments monitored by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrometry (HRMS) unraveled the SGA biosynthetic pathways from CO2 photosynthates via early precursors to the SGAs. After a pulse of ~ 700 ppm 13CO2 for four hours, followed by a chase period for seven days, specific 13C-distributions were detected in SGAs from the leaves of the labeled plant. NMR analysis determined the positional 13C-enrichments in α-solanine and α-chaconine characterized by 13C2-pairs in their aglycones. These patterns were in perfect agreement with a mevalonate-dependent biosynthesis of the isopentenyl diphosphate and dimethylallyl diphosphate precursors. The 13C-distributions also suggested cyclization of the 2,3-oxidosqualene precursor into the solanidine aglycone backbone involving a non-stereoselective hydroxylation step of the sterol a mixture of 25S-/25R-epimers of the SGAs.

α-Solanine Inhibits Proliferation, Invasion, and Migration, and Induces Apoptosis in Human Choriocarcinoma JEG-3 Cells In Vitro and In Vivo.

α-Solanine, a bioactive compound mainly found in potato, exhibits anti-cancer activity towards multiple cancer cells. However, its effects on human choriocarcinoma have not been evaluated. In the present study, we investigated the effect of α-solanine on cell proliferation and apoptosis in human choriocarcinoma in vitro and in vivo. The results showed that α-solanine, at concentrations of 30 µM or below, did not affect the cell viability of the choriocarcinoma cell line JEG-3. However, colony formation was significantly decreased and cell apoptosis was increased in response to 30 µM α-solanine. In addition, α-solanine (30 µM) reduced the migration and invasion abilities of JEG-3 cells, which was associated with a downregulation of matrix metalloproteinases (MMP)-2/9. The in vivo findings provided further evidence of the inhibition of α-solanine on choriocarcinoma tumor growth. α-Solanine suppressed the xenograft tumor growth of JEG-3 cells, resulting in smaller tumor volumes and lower tumor weights. Apoptosis was promoted in xenograft tumors of α-solanine-treated mice. Moreover, α-solanine downregulated proliferative cellular nuclear antigen (PCNA) and Bcl-2 levels and promoted the expression of Bax. Collectively, α-solanine inhibits the growth, migration, and invasion of human JEG-3 choriocarcinoma cells, which may be associated with the induction of apoptosis.

The biosynthetic pathway of potato solanidanes diverged from that of spirosolanes due to evolution of a dioxygenase.

Potato (Solanum tuberosum), a worldwide major food crop, produces the toxic, bitter tasting solanidane glycoalkaloids α-solanine and α-chaconine. Controlling levels of glycoalkaloids is an important focus on potato breeding. Tomato (Solanum lycopersicum) contains a bitter spirosolane glycoalkaloid, α-tomatine. These glycoalkaloids are biosynthesized from cholesterol via a partly common pathway, although the mechanisms giving rise to the structural differences between solanidane and spirosolane remained elusive. Here we identify a 2-oxoglutarate dependent dioxygenase, designated as DPS (Dioxygenase for Potato Solanidane synthesis), that is a key enzyme for solanidane glycoalkaloid biosynthesis in potato. DPS catalyzes the ring-rearrangement from spirosolane to solanidane via C-16 hydroxylation. Evolutionary divergence of spirosolane-metabolizing dioxygenases contributes to the emergence of toxic solanidane glycoalkaloids in potato and the chemical diversity in Solanaceae.

α-Solanine Causes Cellular Dysfunction of Human Trophoblast Cells via Apoptosis and Autophagy.

The trophoblast, an embryonic tissue, exerts a crucial role in the processes of implantation and placentation. Toxins in food can cause malfunction of trophoblasts, resulting in apoptosis, oxidative stress, and abnormal angiogenesis. α-solanine, a steroidal glycoalkaloid, has antitumor properties on several cancer cells. However, its effect on human trophoblasts has not been elucidated. In this study, human extravillous trophoblast HTR-8/SVneo cells were exposed to α-solanine. Cellular functions including proliferation, migration, invasion, tube formation, and apoptosis were assessed. To monitor autophagic flux, trophoblasts were transfected with a mCherry-GFP-LC3B vector using lentiviral transduction, and expression of autophagy-related biomarkers including Beclin 1, Atgl3, and microtubule-associated protein 1 light chain-3 (MAP1-LC3) were detected. The results show that application of 20 µM α-solanine or above inhibited the cell viability, migration, invasion, and tube formation of the human trophoblast. Cell cycle was arrested at S and G2/M phases in response to 30 µM α-solanine. α-solanine induced apoptosis of HTR-8/SVneo cells and triggered autophagy by increasing the autophagic gene expression and stimulating the formation of autophagosome and autophagic flux. In conclusion, α-solanine can impair the functions of human trophoblast cells via activation of cell apoptosis and autophagy.

Alpha Solanine: A Novel Natural Bioactive Molecule with Anticancer Effects in Multiple Human Malignancies.

Cancer is one of the leading causes of death worldwide. Despite improvement in existing treatment modalities and addition of new anticancer drugs in the cancer clinic, cancer associated mortalities are continuously increasing. It is therefore, necessary to explore alternative treatment options to reduce the burden of cancer. In recent years, there is growing concern toward the use of natural products for treating cancer because of their ability to target multiple signaling molecules. α-solanine is a glycolalkaloid mainly present in potato tuber and Nightshade family plants. It possesses anti-pyretic, anti-diabetic, anti-allergic, anti-inflammatory and antibiotic activities. In recent years, α-solanine has been explored for its anticancer activity and showed promising results. Among all sources, potato peel contains adequate concentration of α-solanine. Every year, a large volume of potato peel is produced as a waste or sold at low cost. So α-solanine can be proved as an effective and cheap source for cancer therapy. The aim of this review is to summarize the recent data on anticancer activity of α-solanine and discuss it as a potential lead for cancer therapy.

Solanine Inhibits Immune Escape Mediated by Hepatoma Treg Cells via the TGFß/Smad Signaling Pathway.

OBJECTIVE: To observe the inhibitory effect of solanine on regulatory T cells (Treg) in transplanted hepatoma mice and to study the mechanism of solanine inhibiting tumor growth. METHODS: The levels of Treg cells and IL-2, IL-10, and TGFß in the blood of patients with liver cancer were detected by flow cytometry and ELISA, respectively. A mouse hepatocellular carcinoma (HCC) graft model was established and randomly divided into four groups: control group, solanine group, TGFß inhibitor group (SB-431542), and solanine +TGFß inhibitor combined group. Tumor volume of each group was recorded, tumor inhibition rate was calculated, and tumor metastasis was counted. The proportion of CD4+CD25+Foxp3+ Treg in transplanted tumor tissues was detected by flow cytometry. The expression levels of Foxp3 and TGFß in transplanted tumor tissues were detected by quantitative fluorescence PCR. RESULTS: Compared with healthy people, Treg cells and IL-2, IL-10, and TGFß contents in peripheral blood of liver cancer patients were increased. The results of the transplanted tumor model in mice showed that the tumor volume of the transplanted mice in the solanine group and the TGFß inhibitor mice was reduced compared with the control group. The combined group had the smallest tumor volume. The proportion of CD4+CD25+Foxp3+ Treg in the transplanted tumor tissues of mice in the solanine treatment group was significantly lower than that in the control group. The expressions of Foxp3 and TGFß in the transplanted tumor tissues of mice in the solanine group were significantly lower than those in the control group. CONCLUSION: Solanine may enhance the antitumor immune response by downregulating the proportion of CD4+CD25+ Treg and the expression of Foxp3 and TGFß in tumor tissues.