An antitumor arabinan from Glehnia littoralis activates immunity and inhibits angiogenesis.

Glehnia littoralis is an edible plant with significant medicinal value. To further elucidate the potential functional components for developing antitumor agents or functional foods, the polysaccharides in this plant were investigated, and a homogeneous polysaccharide, GLP90-2, was obtained through extraction and ethanol precipitation. By employing methylation, GC-MS, FT-IR, and NMR analysis, GLP90-2 was identified as an arabinan having a molecular weight of 7.76 × 103 g/mol and consisting of three types of residues: α-l-Araf-(1→, →5)-α-l-Araf-(1→, and →3,5)-α-l-Araf-(1→. The subsequent functional analysis revealed that GLP90-2 suppressed tumor development and metastasis in a zebrafish model. Mechanistic studies have shown that GLP90-2 promoted the maturation of DC2.4 cells and macrophages and enhanced the expression of immune-related cytokines, which may be attributed to the interaction between GLP90-2 and TLR-4. Additionally, GLP90-2 exhibited a strong interaction with PD-1, contributing to the activation of immunity. Furthermore, GLP90-2 suppressed angiogenesis in the transgenic zebrafish model, and this impact may be ascribed to the modulation of the VEGF/VEGFR-2 signaling pathway. All the results indicate that GLP90-2 demonstrates a strong tumor immunotherapy effect in vivo and has high potential for development.

Preparation and photothermal therapy of gold nanorods modified by Belamcanda chinensis (L.) DC polysaccharide.

In recent years, the application of nanoparticles formed by coupling metal nanomaterials of photothermal therapy with polysaccharides as modified carriers in the targeted treatment of liver cancer has attracted extensive attention. In the present work, an undescribed homogeneous polysaccharide BCP50-2 was obtained from Belamcanda chinensis (L.) DC. The structural analysis displayed that BCP50-2 contained galactose and a small amount of arabinose, and was mainly composed of six monosaccharide residues: →3,5)-α-l-Araf-(1→, →4)-ß-d-Galp-(1→, →4,6)-ß-d-Galp-(1→, →3)-α-l-Galp-(1→, terminal α-l-Araf, and terminal ß-d-Galp. To enhance the antitumor activity of BCP50-2, BCP50-2-AuNRs were prepared by coupling BCP50-2 with gold nanorods for the treatment of liver cancer. BCP50-2-AuNRs were rod-shaped with a long diameter of 26.8 nm and had good photothermal conversion effects. Under near-infrared (NIR) light irradiation, BCP50-2-AuNRs possessed photothermal effects and suppressed the growth of HepG2, A549, and MCF-7 cells. In addition, BCP50-2-AuNRs inhibited the development of liver cancer by inducing cell apoptosis, arresting the cell cycle in G2/M phases, and inhibiting cell migration. Moreover, BCP50-2-AuNRs inhibited tumor proliferation, migration, and angiogenesis in zebrafish. In summary, BCP50-2-AuNRs may be potentially useful for cancer treatment.

A polysaccharide from Inula japonica showing in vivo antitumor activity by interacting with TLR-4, PD-1, and VEGF.

Polysaccharides, an important class of carbohydrate polymers, are considered as one of the sources of drug molecules. To discover bioactive polysaccharides as potential agents against cancer, a homogeneous polysaccharide (IJP70-1) has been purified from the flowers of Inula japonica, which is a traditional medicinal plant used for various medical indications. IJP70-1 with a molecular weight of 1.019 × 105 Da was mainly composed of →5)-α-l-Araf-(1→, →2,5)-α-l-Araf-(1→, →3,5)-α-l-Araf-(1→, →2,3,5)-α-l-Araf-(1→, →6)-α-d-Glcp-(1→, →3,6)-α-d-Galp-(1→, and t-α-l-Araf. Apart from the characteristics and structure elucidated by various techniques, the in vivo antitumor activity of IJP70-1 was assayed using zebrafish models. In the subsequent mechanism investigation, it was found that the in vivo antitumor activity of IJP70-1 was not cytotoxic mechanism caused, but related to the activation of the immune system and inhibition of angiogenesis by interacting with the proteins toll-like receptor-4 (TLR-4), programmed death receptor-1 (PD-1), and vascular endothelial growth factor (VEGF). The chemical and biological studies have shown that the homogeneous polysaccharide IJP70-1 has the potential to be developed into an anticancer agent.

Preparation and anti-tumor activity of selenium nanoparticles based on a polysaccharide from Paeonia lactiflora.

The combination of selenium and polysaccharides is one of the significant ways to ameliorate the anti-cancer effects of polysaccharides. PLP50-1, a homogeneous polysaccharide purified from the aqueous extract of Paeonia lactiflora, had a molecular weight of 1.52 × 104 Da and consisted of α-D-Glcp-(1→, →4)-α-D-Glcp-(1→, →6)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, and →6)-ß-D-Fruf-(2→. PLP50-1 showed weak anti-tumor effects against A549 cells. To ameliorate the activity of PLP50-1, the complex nanoparticles combining P. lactiflora polysaccharide with selenium were constructed successfully. Structural properties of the polysaccharide-based selenium nanoparticles (PLP-SeNPs) were clarified using various means. The results displayed that a kind of monodisperse spherical nanoparticles containing high selenium content (39.1 %) with controllable size was constructed and showed satisfactory stability. The cellular anti-tumor assay indicated that PLP-SeNPs had stronger antiproliferative activity against A549 cells than PLP50-1. Additionally, the zebrafish experiments displayed that PLP-SeNPs inhibited the proliferation and migration of A549 cells significantly and blocked the angiogenesis.

Structure, selenization modification, and antitumor activity of a glucomannan from Platycodon grandiflorum.

Platycodon grandiflorum is consumed popularly as a nutritional and healthy plant in East Asia, which has multiple medicinal functions. As an exploration to elucidate the beneficial ingredients, an acetylated glucomannan (PGP40-1) was purified from P. grandiflorum. Structural analysis showed that PGP40-1 was composed of →4)-ß-Manp-(1→, →4)-ß-Glcp-(1→, →6)-ß-Glcp-(1→, and terminal α-Glcp-(1→. PGP40-1 was found to possess weak antitumor activity in vitro, which was thus modified to afford a selenized polysaccharide (Se-PGP40-1) by the HNO3/Na2SeO3 method. Se-PGP40-1 showed significant antitumor activity in cell and zebrafish models, which could inhibit tumor proliferation and migration by inducing cell apoptosis and blocking angiogenesis. The research not only clarifies the ingredients of P. grandiflorum with high economical value, but also affords a potential antitumor agent originating from the plant polysaccharide.

Cratoxylumxanthone C, a natural xanthone, inhibits lung cancer proliferation and metastasis by regulating STAT3 and FAK signal pathways.

To discover phytochemicals as lead compounds for cancer treatment, cratoxylumxanthone C, a natural xanthone, was obtained from Cratoxylum cochinchinense (Lour.) Bl., for which there have been no reports on the biological effects against cancer. Our study revealed that cratoxylumxanthone C had significant anti-tumor activity by inducing apoptosis, augmenting cellular reactive oxygen species (ROS), and arresting cell circle. The mechanistic examination showed the inhibition of A549 cell proliferation and metastasis by cratoxylumxanthone C was coupled with the signal transducer and activator of transcription 3 (STAT3) and focal adhesion kinase (FAK) signaling pathways. Furthermore, the zebrafish models confirmed its significant in vivo anti-tumor activity, in which cratoxylumxanthone C inhibited tumor proliferation and metastasis and suppressed the angiogenesis. Comprehensively, these cellular and zebrafish experiments implied that cratoxylumxanthone C may have the potential to become an anti-tumor agent for lung cancer, especially non-small cell lung cancer (NSCLC).

Structure, anti-tumor activity, and potential anti-tumor mechanism of a fungus polysaccharide from Fomes officinalis.

In our ongoing process of discovering bioactive macromolecules, a homogeneous polysaccharide (FOP80-1) was first purified from Fomes officinalis. FOP80-1 with molecular weight of 4560 Da was mainly composed of →3)-d-Galp-(1→, →4)-ß-d-Manp-(1→, →6)-α-d-Glcp-(1→, →3,6)-d-Glcp-(1→, and t--d-Glcp. Besides the structure features, the anti-tumor activity and potential mechanism of FOP80-1 were also investigated. The cellular and zebrafish experiments revealed that FOP80-1 inhibited tumor proliferation, invasion, and metastasis by increasing ROS, arresting cell cycle, inducing apoptosis, and suppressing angiogenesis. Corresponding to the inhibition of angiogenesis, the surface plasmon resonance (SPR) experiments revealed that FOP80-1 had good affinity with VEGF, a crucial protein to regulate angiogenesis. Molecular docking indicated that FOP80-1 could interact with the protein VEGF.

A natural xanthone suppresses lung cancer growth and metastasis by targeting STAT3 and FAK signaling pathways.

BACKGROUND: Nonsmall-cell lung cancer (NSCLC) is one of the most common malignant tumors, and the current drugs have not achieved ideal therapeutic effects. The abnormal activation of STAT3 and FAK signal transduction in tumor cells is highly correlated with their proliferation and migration ability. Therefore, bioactive compounds that can inhibit STAT3 and FAK activation have the potential to become agents to treat NSCLC. PURPOSE: This study aims to discover new antitumor compounds from Garcinia xipshuanbannaensis and investigate the molecular mechanism by which they inhibit lung cancer proliferation and metastasis in vivo and in vitro, all of which may lead to obtainment of a potential antitumor agent. METHODS: Xipsxanthone H was obtained by various chromatography methods (including silica gel, medium pressure liquid chromatography (MPLC), and preparative high-performance liquid chromatography (HPLC)). 1D and 2D nuclear magnetic resonance (NMR) spectra were used to analyze the structure. Cell viability and wound healing assays were employed to detect changes in the proliferation and migration of cancer cells. Cell cycle and apoptosis were analyzed by flow cytometry. The protein expression of STAT3 and FAK signaling pathways affected by xipsxanthone H was determined by Western blotting. The zebrafish model was used to evaluate the in vivo effects of xipshantone H on tumor proliferation and metastasis. Molecular docking was utilized to explore the interaction between xipsxanthone H and STAT3. Cellular thermal shift assays (CETSAs) were employed to explore the possible target of xipsxanthone H. RESULTS: The novel compound xipsxanthone H was purified and characterized from G. xipshuanbannaensis. Xipsxanthone H exhibited strong anti-proliferation activity in a variety of tumor cell lines. In addition to inducing reactive oxygen species (ROS) production and arresting the cell cycle, mechanistic studies demonstrated that xipsxanthone H suppressed STAT3 and FAK phosphorylation and regulated the downstream protein expression of the STAT3 and FAK signaling pathways. The in vivo studies using the zebrafish model revealed that xipsxanthone H inhibited tumor proliferation, metastasis, and angiogenesis. CONCLUSIONS: A new xanthone was obtained from G. xipshuanbannaensis, and this compound had the property of inhibiting tumor proliferation and metastasis by targeting STAT3 and FAK signaling pathways in NSCLC. These findings suggested that xipsxanthone H might be a potential candidate agent for NSCLC treatment.

Construction of inulin-based selenium nanoparticles to improve the antitumor activity of an inulin-type fructan from chicory.

Cancer has become one of the leading causes of death worldwide. It is urgent to develop new antitumor drugs with high efficiency and low toxicity. In this study, an inulin-type fructan CIP70-1 was purified and characterized from chicory and showed weak antitumor activity. To improve its antitumor effects, inulin-based selenium nanoparticles (CIP-SeNPs) were constructed and characterized. CIP-SeNPs were spherical nanoparticles (60 nm), which remained stable in water for more than 3 months. A cellular antitumor assay revealed that CIP-SeNPs had stronger inhibitory effects on cancer cells (MCF-7, A549, and HepG2) than CIP70-1 alone. Furthermore, the in vivo antitumor effects of CIP-SeNPs were confirmed using zebrafish models. The results showed that CIP-SeNPs significantly inhibited the proliferation and migration of tumors as well as the angiogenesis of transgenic zebrafish in the concentration range of 1-4 µg/mL.

The Antitumor Activity and Mechanism of a Natural Diterpenoid From Casearia graveolens.

Casearlucin A, a diterpenoid obtained from Casearia graveolens, has been reported to possess strong cytotoxic activity. However, the in vivo anti-tumor effects and the action mechanism of casearlucin A remain poorly understood. Our study revealed that casearlucin A arrested cell cycle at G0/G1 stage and induced cell apoptosis in cell level. Additionally, casearlucin A inhibited HepG2 cell migration via regulating a few of metastasis-related proteins. Furthermore, it inhibited tumor angiogenesis in zebrafish in vivo. More importantly, casearlucin A significantly inhibited cell proliferation and migration in an in vivo zebrafish xenograft model. Collectively, these results are valuable for the further development and application of casearlucin A as an anticancer agent.

Construction and antitumor activity of selenium nanoparticles decorated with the polysaccharide extracted from Citrus limon (L.) Burm. f. (Rutaceae).

Selenium nanoparticles (SeNPs), a potential cancer therapeutic agent, have attracted widespread attention owing to their high bioavailability and remarkable anticancer activity. Nevertheless, the poor water solubility and dispersibility of SeNPs seriously limit their applications. In the present study, we synthesized stable and individual spherical selenium nanoparticles (CL90-Tw-SeNP2) with an average diameter of approximately 79 nm using a polysaccharide extracted from Citrus limon (CL90) and Tween-80 as the decorator and stabilizers. The proportion of selenium in CL90-Tw-SeNP2 was 10.6%. CL90-Tw-SeNP2 possessed high stability and good dispersion in water for more than three months. The subsequent biological assay revealed that CL90-Tw-SeNP2 showed remarkable antitumor effects against HepG2 cells, with an IC50 value of 49.13 µg/mL, by inducing cell apoptosis. Furthermore, an in vivo zebrafish assay to explore possible applications indicated that CL90-Tw-SeNP2 could inhibit the proliferation and migration of tumors and the zebrafish angiogenesis. These results indicated that CL90-Tw-SeNP2 could be a potential agent for cancer treatment, especially against human liver hepatoma cancer.