Bulbs Of Ornithogalum Saundersiae Research Articles

Elucidation of OSW-1-Induced Stress Responses in Neuro2a Cells.

OSW-1, a steroidal saponin isolated from the bulbs of Ornithogalum saundersiae, is a promising compound for an anticancer drug; however, its cytotoxic mechanisms have not been fully elucidated. Therefore, we analyzed the stress responses triggered by OSW-1 in the mouse neuroblastoma cell line Neuro2a by comparing it with brefeldin A (BFA), a Golgi apparatus-disrupting reagent. Among the Golgi stress sensors TFE3/TFEB and CREB3, OSW-1 induced dephosphorylation of TFE3/TFEB but not cleavage of CREB3, and induction of the ER stress-inducible genes GADD153 and GADD34 was slight. On the other hand, the induction of LC3-II, an autophagy marker, was more pronounced than the BFA stimulation. To elucidate OSW-1-induced gene expression, we performed a comprehensive gene analysis using a microarray method and observed changes in numerous genes involved in lipid metabolism, such as cholesterol, and in the regulation of the ER-Golgi apparatus. Abnormalities in ER-Golgi transport were also evident in the examination of secretory activity using NanoLuc-tag genes. Finally, we established Neuro2a cells lacking oxysterol-binding protein (OSBP), which were severely reduced by OSW-1, but found OSBP deficiency had little effect on OSW-1-induced cell death and the LC3-II/LC3-I ratio in Neuro2a cells. Future work to elucidate the relationship between OSW-1-induced atypical Golgi stress responses and autophagy induction may lead to the development of new anticancer agents.

Anticancer Effects and Mechanisms of OSW-1 Isolated From Ornithogalum saundersiae: A Review.

For centuries, cancer has been a lingering dark cloud floating on people’s heads. With rapid population growth and aging worldwide, cancer incidence and mortality are growing rapidly. Despite major advances in oncotherapy including surgery, radiation and chemical therapy, as well as immunotherapy and targeted therapy, cancer is expected be the leading cause of premature death in this century. Nowadays, natural compounds with potential anticancer effects have become an indispensable natural treasure for discovering clinically useful agents and made remarkable achievements in cancer chemotherapy. In this regards, OSW-1, which was isolated from the bulbs of Ornithogalum saundersiae in 1992, has exhibited powerful anticancer activities in various cancers. However, after almost three decades, OSW-1 is still far from becoming a real anticancer agent for its anticancer mechanisms remain unclear. Therefore, in this review we summarize the available evidence on the anticancer effects and mechanisms of OSW-1 in vitro and in vivo, and some insights for researchers who are interested in OSW-1 as a potential anticancer drug. We conclude that OSW-1 is a potential candidate for anticancer drugs and deserves further study.

OSW-1 inhibits tumor growth and metastasis by NFATc2 on triple-negative breast cancer.

OSW‐1 is a natural compound extracted from the bulbs of Ornithogalum saundersiae in 1992. It has been shown strong antitumor activities in various cancer cells. However, the effects of OSW‐1 on tumor growth and metastasis in breast cancer are still poorly understood. In our research, we showed that OSW‐1 had a strong anticancer effect on breast cancer cells, but lower toxicity to normal cells. Accordingly, it also revealed significant inhibition of tumor growth by OSW‐1 in xenograft model. In addition, we performed Annexin V/PI‐labeled flow cytometric assay and TUNEL assay and showed that OSW‐1 inhibited tumor growth by inducing apoptosis. Furthermore, we carried out transwell assays and found that OSW‐1 significantly repressed the migratory and invasive capabilities of triple‐negative breast cancer (TNBC) cells via mediating epithelial‐mesenchymal transition. Besides, OSW‐1 also could inhibit metastasis in an orthotopic model and resulted in a longer survival compared with control group. Finally, we performed RNA‐sequencing and cellular functions to investigate the molecular mechanism of how OSW‐1 inhibits TNBC, and identified NFATc2 may as a pivotal factor for OSW‐1‐mediated effects on cell death, tumor growth, invasion, and migration.

Interactions of OSW-1 with Lipid Bilayers in Comparison with Digitonin and Soyasaponin

OSW-1, a unique steroidal saponin isolated from the bulbs of Ornithogalum saundersiae, has potent cell-growth inhibition activity. In this study, we conducted fluorescence measurements and microscopic observations using palmitoyloleoylphosphatidylcholine (POPC)-cholesterol (Chol) bilayers to evaluate the membrane-binding affinity of OSW-1 in comparison with another steroidal saponin, digitonin, and the triterpenoid saponin, soyasaponin Bb(I). The membrane activities of these saponins were evaluated using calcein leakage assays and fitted to the binding isotherm by changing the ratios of saponin-lipids. Digitonin showed the highest binding affinity for the POPC-Chol membrane (Kapp = 0.38 μM-1) and the strongest membrane disruptivity in the bound saponin-lipid ratio at the point of 50% calcein leakage (r50 = 0.47) occurrence. OSW-1 showed slightly lower activity (Kapp = 0.31 μM-1; r50 = 0.78), and the soyasaponin was the lowest in the membrane affinity and the calcein leakage activity (Kapp = 0.017 μM-1; r50 = 1.66). The effect of OSW-1 was further assessed using confocal microscopy in an experiment utilizing DiI and rhodamine 6G as the fluorescence probes. The addition of 30 μM OSW-1 induced inward membrane curvature in some giant unilamellar vesicles (GUVs). At the higher OSW-1 concentration (58 μM, r50 = 0.78) where the 50% calcein leakage was observed, the morphology of some GUVs became elongated. With digitonin at the corresponding concentration (35 μM, r50 = 0.47), membrane disruption and formation of large aggregates in aqueous solution were observed, probably due to a detergent-type mechanism. These saponins, including OSW-1, required Chol to exhibit their potent membrane activity although their mechanisms are thought to be different. At the effective concentration, OSW-1 preferably binds to the bilayers without prominent disruption of vesicles and exerts its activity through the formation of saponin-Chol complexes, probably resulting in membrane permeabilization.

Seven new 1-oxygenated cholestane glycosides from Ornithogalum saundersiae

As the continuous scientific research, seven new 1-oxygenated cholestane glycosides named osaundersiosides 1 A − 1 G were isolated from an EtOH extract of the bulbs of Ornithogalum saundersiae. Their structures were deduced by means of spectroscopic data, chemical evidence and the results of hydrolytic cleavage. The cytotoxicity and anti-inflammatory effects of osaundersiosides 1 A − 1 G were evaluated, but none of them displayed significant activities.

Effects of Chitooligosaccharide Coating Combined with Selected Ionic Polymers on the Stimulation of Ornithogalum saundersiae Growth.

Recently, agricultural and horticultural sectors have shown an increased interest in the use of biopolymers and their derivatives as growth biostimulators. So far, coating is a little known method of applying the biostimulators. Our three-year study investigated coating the bulbs of Ornithogalum saundersiae with chitooligosaccharide (COS), sodium alginate, carrageenan, gellan gum and xanthan gum. The coating method was based on the formation of polyelectrolyte complexes. The COS with 48,000 g mol−1 molecular weight was contained by means of controlled free-radical degradation. Biopolymer coatings stimulated plant growth and flowering, total chlorophyll content, total polyphenol content and the levels of nitrogen, phosphorus, potassium and boron. The plants grown from the bulbs coated with COS + gellan gum exhibited the most vigorous growth, were first to flower, showed the highest antioxidant activity (DPPH), and the greatest content of pigments, polyphenols, l-ascorbic acid, potassium, phosphorus, zinc and manganese. These results suggest COS formulated with gellan gum shows promise as a potential biostimulator of plant growth.

Sterol-recognition ability and membrane-disrupting activity of Ornithogalum saponin OSW-1 and usual 3-O-glycosyl saponins

OSW-1 is a structurally unique steroidal saponin isolated from the bulbs of Ornithogalum saundersiae, and has exhibited highly potent and selective cytotoxicity in tumor cell lines. This study aimed to investigate the molecular mechanism for the membrane-permeabilizing activity of OSW-1 in comparison with those of other saponins by using various spectroscopic approaches. The membrane effects and hemolytic activity of OSW-1 were markedly enhanced in the presence of membrane cholesterol. Binding affinity measurements using fluorescent cholestatrienol and solid-state NMR spectroscopy of a 3-d-cholesterol probe suggested that OSW-1 interacts with membrane cholesterol without forming large aggregates while 3-O-glycosyl saponin, digitonin, forms cholesterol-containing aggregates. The results suggest that OSW-1/cholesterol interaction is likely to cause membrane permeabilization and pore formation without destroying the whole membrane integrity, which could partly be responsible for its highly potent cell toxicity.

Structural Characterization of Cholestane Rhamnosides from Ornithogalum saundersiae Bulbs and Their Cytotoxic Activity against Cultured Tumor Cells.

Previous phytochemical studies of the bulbs of Ornithogalum saundersiae, an ornamental perennial plant native to South Africa, resulted in the isolation of 29 new cholestane glycosides, some of which were structurally unique and showed potent cytotoxic activity against cultured tumor cell lines. Therefore, we aimed to perform further phytochemical examinations of methanolic extracts obtained from Ornithogalum saundersiae bulbs, isolating 12 new cholestane rhamnosides (1–12) and seven known compounds (13–19). The structures of the new compounds (1–12) were identified via NMR-based structural characterization methods, and through a sequence of chemical transformations followed by spectroscopic and chromatographic analysis. The cytotoxic activity of the isolated compounds (1–19) and the derivatives (1a and 6a) against HL-60 human promyelocytic leukemia cells and A549 human lung adenocarcinoma cells was evaluated. Compounds 10–12, 16, and 17 showed cytotoxicity against both HL-60 and A549 cells. Compound 11 showed potent cytotoxicity with an IC50 value of 0.16 µM against HL-60 cells and induced apoptotic cell death via a mitochondrion-independent pathway.

Effect of OSW-1 on microRNA expression profiles of hepatoma cells and functions of novel microRNAs

3β,16β,17α-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-β-D-xylopyranosyl)-(1→3)- (2-O-acet​yl-α-L-arabinopyranoside) (OSW-1) is a member of the cholestane saponin family, which was first isolated from the bulbs of Ornithogalum saundersiae and previously reported to be cytotoxic against several types of malignant cells. However, its antitumor mechanism remains unclear. Therefore, we investigated microRNA (miRNA) expression profiles in order to explore the antitumor activities of OSW-1. Furthermore, following study of differentially expressed miRNAs, the function of novel miRNAs and OSW-1 was determined using known miRNAs and anticarcinogens. The present study demonstrated that treatment with OSW-1 leads to the upregulation and downregulation of a large set of tumor-related miRNAs, including miR-299, miR-1908, miR-125b, miR-187a, miR-1275, hav1-miR-H6-3p, miR-181, miR-210, miR-483, miR-126, miR-208 and others. Notably, miR-141, miR-142, miR-200C and miR-1275 were found to be upregulated by OSW-1 and doxorubicine, as compared with doxorubicine alone. Additionally, the expression fold-change of miR-142-3P was ~58 times higher than its expression with a different treatment. These miRNAs are linked to cancer, including proliferation, differentiation, apoptosis, cell adhesion, migration, polarity and epithelial to mesenchymal transition (EMT).

Structures and Biological Activities of Plant Glycosides: Cholestane Glycosides from Ornithogalum Saundersiae, O. Thyrsoides and Galtonia Candicans, and Their Cytotoxic and Antitumor Activities

Systematic phytochemical screening of higher pants using a cytotoxicity-guided fractionation procedure resulted in the isolation from the bulbs of Ornithogalum saundersiae (Liliaceae) an acylated cholestane diglycoside, 17α-hydroxy-16β-[(O-(2-O-p-methoxybenzoyl-β-D-xylopyranosyl)-(1→3)-2-O-acetyl-α-L-arabinopyranosyl)oxy]cholest-5-en-22-one, tentatively named OSW-1. In vitro cytotoxic and in vivo antitumor screening of OSW-1 revealed that it is a possible candidate as a novel anticancer agent. Furthermore, more than 20 OSW-1-related compounds were isolated, not only from the bulbs of O. saundersiae, but also from those of O. thyrsoides and Galtonia candicans, which are taxonomically related to O. saundersiae. In vitro cytotoxic evaluation of all the isolated compounds and their semi-synthetic analogues allowed the structure-activity relationships of the OSW-1 derivatives to be established. In addition, these three plants were found to produce a series of novel cholestane glycosides with a new rearranged side-chain moiety, 24(23→22)abeo-cholestane, some of which showed potent cytotoxic activity against HL-60 leukemia cells.

Synthesis of a Highly Potent Antitumor Saponin OSW-1 and its Analogues

Twelve years ago a group of cholestane glycosides was isolated from the bulbs of Ornithogalum saundersiae, a species of the lily family without any medicinal folklore background. Similar glycosides were recently isolated from Galtonia candicans. The major component of the mixture of saponins, OSW-1, exhibited sub-nanomolar antineoplastic activity. While OSW-1 is exceptionally cytotoxic against various tumor cells, it shows little toxicity with normal human pulmonary cells. In this review article the synthetic efforts towards OSW-1 and related cholestane glycosides, as well as the preliminary results of the structure–activity relationship study are presented.

Approaches Towards the Synthesis of Cephalostatins, Ritterazines and Saponins from Ornithogalum saundersiae — New Natural Products with Cytostatic Activity

AbstractFor Abstract see ChemInform Abstract in Full Text.

Approaches Towards the Synthesis of Cephalostatins, Ritterazines and Saponins from Ornithogalum saundersiae - New Natural Products With Cytostatic Activity

Secondary metabolites of marine invertebrates continue to attract the attention of organic chemists, biochemists, and pharmacologists due to their novel structures and potent biological activities. One such example is cephalostatin 1 isolated from the Indian Ocean hemichordate Cephalodiscus gilchristi, which exhibited remarkable cytotoxic activity against a broad spectrum of malignant tumor cells. Similar marine alkaloids (e.g. ritterazine G) were found in the lipophilic extract of the tunicate Ritterella tokioka collected off the coast of Japan. These very potent compounds, cephalostatins and ritterazines, belong to the large family of trisdecacyclic pyrazines, consisting of two steroid units. The two steroid halves of cephalostatin 1 and other highly cytotoxic members of the family are different. The biological activity of the dimeric steroid-pyrazine marine alkaloids and their limited availability coupled with the new and intriguing structure make them an attractive challenge for the synthetic organic chemists. A few years ago a group of cholestane glycosides was isolated from the bulbs of Ornithogalum saundersiae, a species of the lily family without any medicinal folkloric background. Similar glycosides were recently isolated from Galtonia candicans. The major component of the mixture of saponins, OSW-1, exhibited sub-nanomolar antineoplastic activity. While OSW-1 is exceptionally cytotoxic against various tumor cells, it showed little toxicity to normal human pulmonary cells. The cytotoxicity profile of OSW-1 against different cancer cell lines was found to be surprisingly similar to that of the cephalostatins, which appears to imply a related mechanism of action. In this review article the synthetic efforts towards these compounds are described. Keywords: Cephalostatins, cytotoxicity, glycosides

A Novel Rearranged Cholestane Glycoside with a d-Lactone Ring System from Ornithogalum saundersiae Bulbs

The bulbs of Ornithogalum saundersiae have been revealed to contain a variety of cholestane glycosides. Further chemical investigation of the MeOH extract of O. saundersiae bulbs have resulted in the isolation of a novel 24(23→22)abeo-cholestane glycoside with a δ-lactone system (1). The structure of 1 was elucidated on the basis of extensive spectroscopic analysis and the result of acid hydrolysis.

Cytotoxic Cholestane Glycosides from the Bulbs of Ornithogalum saundersiae

Further phytochemical analysis of the bulbs of Ornithogalum saundersiae has yielded two new cytotoxic cholestane triglycosides (1 and 2). The structures of these compounds were determined by spectroscopic analysis, including 2D NMR spectroscopic data, and the results of hydrolytic cleavage. Compounds 1 and 2 and several analogues were evaluated for their cytotoxicity against HL-60 cells.

Saundersiosides C-H, rearranged cholestane glycosides from the bulbs of Ornithogalum saundersiae and their cytostatic activity on HL-60 cells.

Six novel rearranged cholestane glycosides with a six-membered hemiacetal ring system, designated as saundersiosides C-H, were isolated from the bulbs of Ornithogalum saundersiae. Their structures were determined on the basis of spectroscopic analysis and the result of hydrolysis. The conformation of the six-membered hemiacetal ring of the rearranged cholestanes was shown to be almost a boat-form by molecular mechanics and molecular dynamics calculation studies. Among the isolated compounds, saundersioside E, F, G and H with an aromatic acid ester group at the glycoside moiety were found to be highly cytostatic to human leukemia HL-60 cells, showing IC50 values of 0.021, 0.019, 0.063 and 0.052 microM, respectively, which are as potent as those of the clinically applied anticancer agents, etoposide and methotrexate.

Cholestane rhamnosides from the bulbs of Ornithogalum saundersiae.

Phytochemical examination of the bulbs of Ornithogalum saundersiae yielded six cholestane rhamnosides, two of which had previously been isolated from the same plant material. However, detailed spectroscopic analysis of the aglycone led us to revise the configuration of the C-11 hydroxyl group of the latter two and reassign their structures as (22S)-cholest-5-ene-3 beta,11 alpha,16 beta,22-tetrol 16-O-alpha-L-rhamnopyranoside and (22S)-cholesta-5,24-diene-3 beta,11 alpha,16 beta,22-tetrol 16-O-alpha-L-rhamnopyranoside, respectively. The other four are new naturally occurring constituents and their structures were determined to be (22S)-cholest-5-ene-3 beta,11 alpha,16 beta,22-tetrol 16-O-(2,3-di-O-acetyl-alpha-L-rhamnopyranoside), (22S)-cholest-5-ene-3 beta,11 alpha,16 beta,22-tetrol 16-O-{2-O-acetyl-3-O-(3,4,5-trimethoxybenzoyl)-alpha-L-rhamnopyran oside}, (22S)-cholest-5-ene-3 beta,11 alpha,16 beta,22-tetrol 16-O-{2-O-acetyl-3-O-(p-methoxybenzoyl)-alpha-L-rhamnopyranoside} and (22S)-cholesta-5,24-diene-3 beta,11 alpha,16 beta,22-tetrol 16-O-(2,3-di-O-acetyl-alpha-L-rhamnopyranoside), respectively. The isolated compounds were evaluated for their cytostatic activity against leukemia HL-60 cells.

Novel cholestane glycosides from the bulbs of Ornithogalum saundersiae and their cytostatic activity on leukemia HL-60 and MOLT-4 cells

Two novel 24(23→22) abeo-cholestane glycosides with a six-membered hemiacetal ring system and a five-membered acetal ring system ( 2, 3), designated as saundersioside A and B, respectively, together with a new 16,23-epoxy-5β-cholestane glycoside ( 1) were isolated from the bulbs of Ornithogalum saundersiae. Their structures were determined by detailed analysis of the 1H and 13C NMR spectra, including various two-dimensional spectroscopy, and acid-catalyzed hydrolysis. The conformations of the 16,23-epoxy moiety of 1 and the six-membered hemiacetal moiety of 2 and 3 were studied through molecular mechanics and molecular dynamics calculation methods. Compound 3 bearing a p-methoxybenzoyl group at the saccharide part showed potent cytostatic activity on leukemia HL-60 and MOLT-4 cells, and the effect to HL-60 cells was revealed to be mediated partially through induction of apoptosis by cell morphology and DNA fragmentation.

ChemInform Abstract: A New Rearranged Cholestane Glycoside from Ornithogalum saundersiae Bulbs Exhibiting Potent Cytostatic Activities on Leukemia HL‐60 and MOLT‐4 Cells.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A new rearranged cholestane glycoside from ornithogalum saundersiae bulbs exhibiting potent cytostatic activities on leukemia HL-60 and molt-4 cells

A new rearranged cholestane glycoside ( 1) was isolated from Ornithogalum saundersiae bulbs by monitoring the cytostatic activity on leukemia HL-60 cells. Compound 1 was exceptionally cytostatic against HL-60 and MOLT-4 cells, which was revealed to be mediated partially through induction of apoptosis.