Natural Plant-derived Compound Research Articles

Exogenous Application of Methyl Salicylate Induces Defence in Brassica against Peach Potato Aphid Myzus persicae.

Plants use a variety of secondary metabolites to defend themselves against herbivore insects. Methyl salicylate (MeSA) is a natural plant-derived compound that has been used as a plant defence elicitor and a herbivore repellent on several crop plants. The aim of this study was to investigate the effect of MeSA treatment of Brassica rapa subsp. chinensis ('Hanakan' pak choi) on its interactions with peach potato aphids, Myzus persicae, and their natural enemy, Diaeretiella rapae. For this, we selected two concentrations of MeSA (75 mg/L and 100 mg/L). Our results showed that aphid performance was significantly reduced on plants treated with MeSA (100 mg/L). In a cage bioassay, the MeSA (100 mg/L)-treated plants showed lower adult survival and larviposition. Similarly, the MeSA (100 mg/L)-treated plants had a significantly lower aphid settlement in a settlement bioassay. In contrast, the M. persicae aphids did not show any significant difference between the MeSA (75 mg/L)-treated and control plants. In a parasitoid foraging bioassay, the parasitoid D. rapae also did not show any significant difference in the time spent on MeSA-treated and control plants. A volatile analysis showed that the MeSA treatment induced a significant change in volatile emissions, as high numbers of volatile compounds were detected from the MeSA-treated plants. Our results showed that MeSA has potential to induce defence in Brassica against M. persicae and can be utilised in developing sustainable approaches for the management of peach potato aphids.

Evaluation of Inhibitory Effect and Mechanism of Euphorbia Factor L3 against Phytophthora capsici

Phytophthora capsici is a highly destructive phytopathogenic oomycete with a broad host range and is responsible for tremendous losses. Euphorbia factor L3 (EFL3) is a natural plant-derived compound that has been widely studied in medicine and cosmetic applications. In this study, the sensitivity of 105 P. capsici isolates to EFL3 was determined, and the biological activity and physiological effects of EFL3 against P. capsici were investigated. The median effective concentration (EC50) values for EFL3 inhibition mycelial growth and spore germination ranged from 0.66 to 8.94 μg/mL (mean, 2.96 ± 0.91 μg/mL) and 1.63 to 13.16 μg/mL (mean, 5.30 ± 1.64 μg/mL), respectively. EFL3 treatment resulted in cell wall and cell membrane damage of P. capsici, which was revealed by morphological and ultrastructural observations, propidium iodide (PI) and calcofluor white (CFW) staining, and measurements of relative conductivity as well as malondialdehyde (MDA) and glycerol contents. In addition, the contents of phospholipid and cellulose, which are the major components of cell membrane and cell wall, were significantly reduced following EFL3 treatment. Furthermore, EFL3 provided protective as well as curative efficacies against P. capsici on detached tomato leaves and pepper seedlings in vivo. These data show that EFL3 exhibits strong inhibitory activity against P. capsici, thereby suggesting that it could be an effective alternative for controlling P. capsici-induced diseases.

Study on the fungicidal mechanism of glabridin against Fusarium graminearum

Glabridin is a natural plant-derived compound that has been widely used in medicine and cosmetic applications. However, the fungicidal mechanism of glabridin against phytopathogens remains unclear. In this study, we determined the biological activity and physiological effects of glabridin against F. graminearum. Then the differentially expressed proteins of F. graminearum were screened. The EC50 values of glabridin in inhibiting the mycelial growth and conidial germination of F. graminearum were 110.70 mg/L and 40.47 mg/L respectively. Glabridin-induced cell membrane damage was indicated by morphological observations, DiBAC4(3) and PI staining, and measurements of relative conductivity, ergosterol content and respiratory rates. These assays revealed that the integrity of the membrane was destroyed, the content of ergosterol decreased, and the respiratory rate was inhibited. A proteomics analysis showed that 186 proteins were up-regulated and 195 proteins were down-regulated. Mechanically sensitive ion channel proteins related to transmembrane transport and ergosterol biosynthesis ERG4/ERG24, related to ergosterol synthesis were blocked. It is speculated that glabridin acts on ergosterol synthesis-related proteins to destroy the integrity of the cell membrane, resulting in abnormal transmembrane transport and an increased membrane potential. Finally, the morphology of mycelia was seriously deformed, growth and development were inhibited. As a result death was even induced.

Protective Effect of Piceatannol Against Cerebral Ischaemia-Reperfusion Injury Via Regulating Nrf2/HO-1 Pathway In Vivo and Vitro.

Piceatannol is a natural plant-derived compound with protective effects against cardiovascular diseases. However, its effect on cerebral ischaemia-reperfusion injury (CIRI) induced by oxidative stress remains unclear. This study aimed to investigate piceatannol's antioxidation in CIRI. An in vitro oxygen-glucose deprivation followed by reoxygenation model was used and cell viability was measured. A middle cerebral artery occlusion followed by reperfusion model was used in vivo. Neurological function, encephalisation quotient, oedema, and volume of the cerebral infarction were then evaluated. The effects of piceatannol on histopathological findings, as well as the ultrastructure of the cortex, were analysed. The activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and lactate dehydrogenase (LDH) and the malondialdehyde (MDA) content was measured both in vitro and in vivo. Finally, the expression of nuclear factor erythroid-2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), and nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 (NQO1) in cerebral tissue was detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting. Our results demonstrated that cell viability in the piceatannol groups was increased. The SOD, GSH-Px activities were increased as LDH activity and MDA content decreased in the piceatannol groups both in vitro and in vivo, reflecting a decrease in oxidative stress. The neurological severity score and infarction volume in the piceatannol groups at doses of 10 and 20mg/kg were lower than those of the model group. Furthermore, the damage seen on histopathological examination was partially attenuated by piceatannol. RT-qPCR and western blot analysis indicated that the expression of Nrf2, HO-1, and NQO1 were significantly increased by piceatannol. The results of the study demonstrate that piceatannol exerts a protective effect against CIRI.

Inhibitory Effects of Isobavachalcone on Tau Protein Aggregation, Tau Phosphorylation, and Oligomeric Tau-Induced Apoptosis.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases without any effective medicine treatments. The neurofibrillary tangles containing hyperphosphorylated tau protein are one important pathological characteristic. Thus, one practicable strategy for AD drug design is to discover compounds that could inhibit tau protein aggregation and/or phosphorylation. In this study, isobavachalcone, a natural plant-derived compound, has been shown to inhibit tau protein aggregation and disaggregate tau fibrils in vitro by directly interacting with tau protein at amino acids I278, V309, etc. It is able to reduce tau phosphorylation at four disease-related sites in vivo by regulating the critical kinase and protein phosphatase, GSK3β and PP2A. The compound also exhibits protection against tau oligomers-induced apoptosis through the mitochondria and ER mediated apoptotic pathways. In summary, isobavachalcone is a promising candidate for further evaluation as a potential preventive and therapeutic medicine for AD.

Genipin improves reproductive health problems caused by circadian disruption in male mice

BackgroundCircadian rhythm disruption impacts a wide range of physiological processes, including fertility. However, the effect of circadian disruption on male spermatogenesis and fertility, and treatments for these effects have been largely unexplored at the molecular level.MethodsIn this study, we examined the effects of genipin on improving the reproductive health problems caused by circadian disruption. Three groups of animals were fed under different conditions: control group (normal T cycle with saline), group of shortened T cycles (Light/Dark = 4 hours/4 hours) with saline, and a group of shortened T cycles with genipin by oral gavage. The male fertility was evaluated by fertility study and pups parameters analysis after successful sexual behavior and mating with female mice. We sacrificed the treated animals after 5 or 10 weeks and collected the testis, sperm and serum for histological analysis, sperm motility assay, and serum hormone detection, respectively. Furthermore, the effect of genipin was assessed by detection of progesterone secretion and steroidogenic key proteins expression, including StAR and CYP11A1, in mouse Leydig tumor MLTC-1 cells.ResultsMale mice exposed to shortened light-dark cycles, much shorter than 24 hours, had reduced fertility with decreased sperm concentrations and sperm motility. Male mice under circadian disruption have reduced testis size and abnormal morphology, leading to lower fertility rates, reduced litter size and pup body weight. Treatment with exogenous genipin, a natural plant-derived compound, alleviated circadian disruption-induced damage to fertility and spermatogenesis and normalized testosterone, dihydrotestosterone (DHT), and androstenedione (ASD) levels in the male mice. The levels of key proteins involved in steroidogenesis, StAR and CYP11A1, were reduced in mouse testes after the circadian disruption, but genipin treatment restored the reduction. The mRNA expression of SRD5A1, which encodes an androgen synthesis enzyme, was also upregulated by genipin treatment. Furthermore, genipin treatment showed a positive effect on steroidogenesis in MLTC-1 cells, resulting in an increase in hormone secretion and the upregulation of StAR and CYP11A1.ConclusionsOur results showed an association between circadian disruption and reproductive health problems in male mice and indicated that treatments with genipin have positive effects on the reproductive health of male mice with circadian rhythm disorders.

Maslinic Acid Induces DNA Damage and Impairs DNA Repair in Human Cervical Cancer HeLa Cells.

Maslinic acid, a natural plant-derived triterpenoid compound, exhibits pharmacological activities, including anti-cancer. In the present study, we investigated the cytotoxic effects of maslinic acid on human cervical cancer HeLa cells in vitro and further investigated the molecular mechanism of maslinic acid-induced DNA damage and repair. Cell viability was measured by flow cytometry. DNA condensation (apoptotic cell death), DNA damage, and DNA fragmentation (DNA ladder) were assayed by DAPI staining, comet assay, and agarose gel electrophoresis, respectively. The expression of DNA damage and repair proteins was assayed by western blotting. Maslinic acid decreased total cell viability and induced DNA condensation, damage, and fragmentation in HeLa cells. Furthermore, maslinic acid elevated the levels of p-ATMSer1981, p-ATRSer428, p53, p-p53Ser151, p-H2A.XSer139, BRCA1 and PARP at 30-40 μM. However, it decreased the levels of DNA-PK and MGMT. Maslinic acid reduced the number of viable HeLa cells by inducing DNA damage and altering the expression of proteins involved in DNA damage and repair.

Resveratrol Reduced Liver Damage After Liver Resection in a Rat Model by Upregulating Sirtuin 1 (SIRT1) and Inhibiting the Acetylation of High Mobility Group Box 1 (HMGB1).

BackgroundLiver failure after resection for liver cancer is associated with increased patient mortality. This study aimed to investigate the mechanism of the protective effects of resveratrol, a natural plant-derived compound, on liver injury in a rat model of partial hepatectomy.Material/MethodsAdult male Sprague-Dawley (SD) rats (n=60) were divided into the sham group (n=20), the liver resection group (n=20), and the liver resection plus resveratrol-treated group (n=20). Liver resection removed 2/3 of the liver resection; resveratrol was given at a dose of 30 mg/kg/day from one week before surgery until death. Liver injury was assessed by serum liver function tests, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl-transferase (γ-GT) and total bilirubin, histological examination of the rat liver, and liver cell apoptosis using the TUNEL assay. High mobility group box 1 (HMGB1) expression was measured by enzyme-linked immunoassay (ELISA). Sirtuin 1 (SIRT1) and acetylated HMGB1 (Ac-HMGB1) expression were detected by Western blot. Normal human liver cells and HepG2 liver cancer cells were incubated with acetylated HMGB1, and albumin production and ammonia elimination assays were performed.ResultsResveratrol reduced postoperative liver injury as shown by reduced ALT, AST, γ-GT, and total bilirubin levels, maintained liver structure, and reduced cell apoptosis. Resveratrol treatment reduced the expression and acetylation levels of HMGB1 via the SIRT1 signaling pathway. Resveratrol reversed Ac-HMGB1 induced dysfunction in liver cells cultured in vitro.ConclusionsResveratrol reduced liver damage after liver resection in a rat model by upregulating SIRT1 and reducing the acetylation of HMGB1.

Resveratrol Suppresses Epithelial-Mesenchymal Transition in GBM by Regulating Smad-Dependent Signaling.

Glioblastoma (GBM) is the most common and malignant intracranial tumor in adults. Despite continuous improvements in diagnosis and therapeutic method, the prognosis is still far away from expectations. The invasive phenotype of GBM is the main reason for the poor prognosis. Epithelial-mesenchymal transition (EMT) is recognized as a participator in this invasive phenotype. Resveratrol, a natural plant-derived compound, is reported to be able to regulate EMT. In the present study, we used TGF-β1 to induce EMT and aimed to evaluate the effect of resveratrol on EMT and to explore the underline mechanism in GBM. Western blotting was used to detect the expression of EMT-related markers, stemness markers, and Smad-dependent signaling. Wound healing assay and transwell invasion assay were performed to evaluate the migratory and invasive ability of GBM cells. Gliosphere formation assay was used to investigate the effect of resveratrol on the ability of self-renewal. Xenograft experiment was conducted to examine the effect of resveratrol on EMT and Smad-dependent signaling in vivo. Our data validated that resveratrol suppressed EMT and EMT-associated migratory and invasive ability via Smad-dependent signaling in GBM cells. We also confirmed that resveratrol obviously inhibited EMT-induced self-renewal ability of glioma stem cells (GSCs) and inhibited EMT-induced cancer stem cell markers Bmi1 and Sox2, suggesting that resveratrol is able to suppress EMT-generated stem cell-like properties in GBM cells. Furthermore, we also showed the inhibitory effect of resveratrol on EMT in xenograft experiments in vivo. Overall, our study reveals that resveratrol suppresses EMT and EMT-generated stem cell-like properties in GBM by regulating Smad-dependent signaling and provides experimental evidence of resveratrol for GBM treatment.

Isovitexin Increases Stem Cell Properties and Protects Against PM2.5 in Keratinocytes.

Background/Aim: Fine airborne particles of Particular Matter of less than 2.5 micrometers (PM 2.5 ) have been recognized as a dominant air contamination causing critical health concerns. Herein, we determined whether isovitexin, a natural plant-derived compound could protect PM2.5-mediated oxidative stress and induce stemness in epidermal cells. Materials and Methods: Cell viability was detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. Reactive oxygen species (ROS) were determined by flow cytometry with 2',7'-dichlorofluorescin diacetate (DCFH-DA). Protein hallmarks of stem cells were examined by western blot analysis. Results: PM2.5 treatment for 30 min increased the levels of intracellular ROS. Pre-treatment of cells with 10-50 μM of isovitexin dramatically inhibited the ROS induced by PM2.5. Antioxidant efficacy of isovitexin was also determined by the ROS scavenging activity against 2,2-diphenyl-2-picrylhydrazyl (DPPH), ABTS and superoxide anion radicals. In addition, we found that isovitexin enhanced the stem cell properties of keratinocytes, indicated by the significant increase in the levels of stem cell proteins. Conclusion: Isovitexin can be potentially used as an effective compound for preventing skin damage.

Genipin Cross-Linking of Elastin and Elastin-Based Proteins.

Genipin is a natural plant-derived compound that covalently cross-links biopolymers into lattice networks with good biocompatibility, controllable swelling, and mechanical properties. This protocol describes the genipin cross-linking of elastic proteins, including tropoelastin and elastin-based polypeptides, through steps of elastin phase-separation upon addition of salt and heat, centrifugation to rapidly concentrate the dense protein phase, and incubation. This method is applicable for the fabrication of elastic materials suitable for use as scaffolds for biomedical applications.

The functional genomic studies of curcumin.

Curcumin is a natural plant-derived compound that has attracted a lot of attention for its anti-cancer activities. Curcumin can slow proliferation of and induce apoptosis in cancer cell lines, but the precise mechanisms of these effects are not fully understood. However, many lines of evidence suggested that curcumin has a potent impact on gene expression profiles; thus, functional genomics should be the key to understanding how curcumin exerts its anti-cancer activities. Here, we review the published functional genomic studies of curcumin focusing on cancer. Typically, a cancer cell line or a grafted tumor were exposed to curcumin and profiled with microarrays, methylation assays, or RNA-seq. Crucially, these studies are in agreement that curcumin has a powerful effect on gene expression. In the majority of the studies, among differentially expressed genes we found genes involved in cell signaling, apoptosis, and the control of cell cycle. Curcumin can also induce specific methylation changes, and is a powerful regulator of the expression of microRNAs which control oncogenesis. We also reflect on how the broader technological progress in transcriptomics has been reflected on the field of curcumin. We conclude by discussing the areas where more functional genomic studies are highly desirable. Integrated OMICS approaches will clearly be the key to understanding curcumin's anticancer and chemopreventive effects. Such strategies may become a template for elucidating the mode of action of other natural products; many natural products have pleiotropic effects that are well suited for a systems-level analysis.

Cinnamaldehyde Ameliorates Cadmium-Inhibited Root Elongation in Tobacco Seedlings via Decreasing Endogenous Hydrogen Sulfide Production.

Cinnamaldehyde (CA) is natural plant-derived compound that has been highly appreciated for its medicinal properties. However, little information is known about the regulation of plant intrinsic physiology by CA. To address these gaps, physiological, histochemical, and biochemical approaches were applied to investigate CA-facilitated cadmium (Cd) tolerance in the roots of tobacco (Nicotiana tabacum) seedlings. Treatment with CdCl2 at 20 μM for 72 h resulted in the significant decrease in root elongation by 40.39% as compared to control. CA alleviated Cd-inhibited root elongation in dose- and time-dependent manners. The addition of CA at 20 μM induced significant increase in root elongation by 42.58% as compared to Cd treatment alone. CA abolished Cd-induced ROS (reactive oxygen species) accumulation, lipid peroxidation, loss of membrane integrity, cell death, and free Cd2+ accumulation in roots. CA blocked the Cd-induced increase in the endogenous H2S level through the down-regulation of d-cysteine desulfhydrase (DCD) expression. H2S scavenger hypotaurine (HT) or potent H2S-biosynthetic inhibitor dl-propargylglicine (PAG) were able mimic the action of CA on the blockade of Cd-induced H2S accumulation, cell death, and growth inhibition. Enhancement of the endogenous H2S level with NaHS (H2S donor) abrogated all the beneficial capabilities of CA, HT, and PAG. Collectively, these results suggest that CA has great potential to confer plant tolerance against Cd stress, which is closely associated with its capability to inhibit Cd-induced H2S production. This study not only provides evidences for the regulation of plant physiology by CA but also sheds new light on the cross-talk between CA and H2S in physiological modulations.

The Fungicidal Activity of Thymol against Fusarium graminearum via Inducing Lipid Peroxidation and Disrupting Ergosterol Biosynthesis.

Thymol is a natural plant-derived compound that has been widely used in pharmaceutical and food preservation applications. However, the antifungal mechanism for thymol against phytopathogens remains unclear. In this study, we identified the antifungal action of thymol against Fusarium graminearum, an economically important phytopathogen showing severe resistance to traditional chemical fungicides. The sensitivity of thymol on different F. graminearum isolates was screened. The hyphal growth, as well as conidial production and germination, were quantified under thymol treatment. Histochemical, microscopic, and biochemical approaches were applied to investigate thymol-induced cell membrane damage. The average EC50 value of thymol for 59 F. graminearum isolates was 26.3 μg·mL−1. Thymol strongly inhibited conidial production and hyphal growth. Thymol-induced cell membrane damage was indicated by propidium iodide (PI) staining, morphological observation, relative conductivity, and glycerol measurement. Thymol induced a significant increase in malondialdehyde (MDA) concentration and a remarkable decrease in ergosterol content. Taken together, thymol showed potential antifungal activity against F. graminearum due to the cell membrane damage originating from lipid peroxidation and the disturbance of ergosterol biosynthesis. These results not only shed new light on the antifungal mechanism of thymol, but also imply a promising alternative for the control of Fusarium head blight (FHB) disease caused by F. graminearum.

3,3′‐Diindolylmethane attenuates LPS‐mediated acute liver failure by regulating miRNAs to target IRAK4 and suppress Toll‐like receptor signalling

Acute liver failure (ALF) is a severe and potentially lethal clinical syndrome. 3,3'-Diindolylmethane (DIM) is a natural plant-derived compound with anti-cancer activities. Recently, DIM has also been shown to have anti-inflammatory properties. Here, we tested the hypothesis that DIM would suppress endotoxin-induced ALF. We investigated the therapeutic potential of DIM in a mouse model of D-galactosamine/Lipopolysaccharide (GalN/LPS)-induced ALF. The efficacy of DIM treatment was assessed by survival, liver histopathology, serum levels of alanine transaminase, pro-inflammatory cytokines and number of activated liver macrophages. Effects of DIM on the expression of two miRNAs, 106a and 20b, and their predicted target gene were measured by qRT-PCR and Western blotting. Effects of DIM on the release of TNF-α from RAW264.7 macrophages transfected with mimics of these miRNAs and activated by LPS was assessed by elisa. DIM treatment protected mice from ALF symptoms and reduced the number of activated liver macrophages. DIM increased expression of miR-106a and miR-20b in liver mononuclear cells and decreased expression of their predicted target gene IL-1 receptor-associated kinase 4 (IRAK4), involved in signalling from Toll-like receptor 4 (TLR4). In vitro transfection of RAW264.7 cells using miRNA mimics of miR-106a and 20b decreased expression of IRAK4 and of TNF-α secretion, following LPS stimulation. DIM attenuated GalN/LPS-induced ALF by regulating the expression of unique miRNAs that target key molecules in the TLR4 inflammatory pathway. DIM may represent a potential novel hepatoprotective agent.

Chemoprevention utility of silibinin and Cdk4 pathway inhibition in Apc −/+ ice

BackgroundColorectal cancer (CRC) is the second leading cause of death from cancer in the United States. Colorectal cancers have a prolonged latency following initiation that may span decades providing ample time for implementing a chemoprevention strategy that could block or reverse the progression to CRC. Cdk4 pathway alterations have been linked to a number of cancers including CRC. In these experiments we focused on the Cdk4 pathway and its role in intestinal tumorigenesis as a possible target in chemoprevention strategies.MethodsWe evaluated the effect of Cdk4 blockade on the prevention of intestinal tumor formation by crossing Cdk4−/− mice to Apc−/+ mice. In addition, we tested the effect of the dietary compound silibinin on the Cdk4 pathway in Apc−/+ mice and HT-29 colon cancer cells in culture.ResultsCdk4−/− mice backcrossed to Apc−/+ mice reduced intestinal adenoma formation compared to Apc−/+ controls. Silibinin effectively targeted the Cdk4 pathway causing hypophosphorylation of the retinoblastoma protein, inhibited cell growth, and induced apoptosis. As a result silibinin blocked the development of intestinal adenomas by 52% in this genetic model (Apc−/+ mice) of early events in colorectal cancer formation. No toxic abnormalities were detected in mice which received silibinin.ConclusionsModification of the Cdk4 pathway using a natural plant-derived compound such as silibinin may be a useful chemopreventive strategy for colorectal carcinomas.

Abstract B57: A natural plant-derived compound, Withaferin A, exploits the stress pathway to induce antitumor immunity.

Abstract Recent research involving chemotherapeutic drugs such as anthracyclines have aided in redefining the definition of apoptosis from a form of cell death that is immunologically silent to the one that can activate an anti-cancer immune response. This form of apoptosis has been characterized as immunogenic cell death (ICD) and possess certain hallmarks such as the cell surface expression of heat shock proteins (HSPs) including HSP70 and HSP90 as well as ER-stress mediated pre-apoptotic expression of the ER chaperone calreticulin (CRT). One of the mechanisms by which ICD occurs is linked to the induction of an unfolded protein response (UPR) due to prolonged chemotherapeutic stress on cancer cells. Our research focuses on the development of Withaferin A (WA), a steroidal lactone derived from the Indian ayurvedic medicinal plant Withania somnifera as a chemoimmunotherapeutic agent. The benefit of using natural plant derived products is their low toxicity, multimodal action and potential ability to enhance the immune system. We initially screened the effect of Withaferin A by microarray analysis on breast cancer cells. WA induced significant alteration of 1160 genes (p-value 0.005). A pathway analysis determined that WA induces a robust heat shock response through up-regulation of several genes related to this pathway including response to unfolded proteins. The gene expression data was confirmed by the induction of intracellular HSP70, HSP40 as well as the UPR marker Bip78 by western blot. Furthermore we are able to demonstrate that WA treatment results in the translocation of known immunogenic HSPs HSP70, CRT and gp96 to the cell surface of several cancer cell lines. Additionally, WA treatment results in the induction of apoptosis and these WA mediated apoptotic cells can confer immunological protection against re-challenge with live tumor cells in vivo. Our long-term goal is to elucidate the anti-tumor immunomodulatory mechanisms of WA. Funded by: American Cancer Society (S.A.) Citation Format: Annalise R. Smith, Darlah Lopez, Samita Andreansky. A natural plant-derived compound, Withaferin A, exploits the stress pathway to induce antitumor immunity. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B57.