pectins and Lung-Neoplasms

Serious side effects of chemotherapy drugs greatly limited the anticancer performance, while targeted drug delivery could improve the therapeutic effect and reduce side effects. In this work, biodegradable hydrogel was fabricated from pectin hydrazide (pec-H) and oxidized carboxymethyl cellulose (DCMC) for localized Silibinin delivery in lung adenocarcinoma treatment. The self-healing pec-H/DCMC hydrogel showed blood compatibility and cell compatibility both in vitro and in vivo, and could be degraded by enzymes. The hydrogel also formed fast fit for injectable applications and showed sustained drug release characteristic sensitive to pH based on acylhydrzone bond cross-linked networks. The Silibinin, as a specific lung cancer inhibiting drug targets TMEM16A ion channel, was loaded into the pec-H/DCMC hydrogel to treat the lung cancer in mice model. The results showed that the hydrogel loaded Silibinin significantly enhanced the anti-tumor efficiency in vivo and greatly reduced the toxicity of the Silibinin. Based on the dual effect of improving efficacy and reducing side effects, the pec-H/DCMC hydrogel with Silibinin loading have broad application prospects to inhibit lung tumor growth in clinic.

Topics: Animals; Carboxymethylcellulose Sodium; Hydrogels; Lung Neoplasms; Mice; Pectins; Silybin

Lung cancer as one of the highest incident malignant tumors did not receive satisfactory chemotherapy due to lack of specific drug targets and targeted drugs. This study screened a new effective lung tumor inhibitor limonin from herbal medicine, which inhibited proliferation and promoted apoptosis of lung adenocarcinoma cells by targeting specific high expressed TMEM16A ion channel. Moreover, a novel biodegradable self-healing hydrogel was prepared from acylhydrazide functionalized carboxymethyl cellulose (CMC-AH) and oxidized pectin (pec-CHO) to reduce the side effects of the limonin to the body. The hydrogels showed fast gelation, good biocompatibility and sustained limonin release property. The limonin-loaded hydrogel significantly inhibited the growth of lung adenocarcinoma in xenografts mice because the limonin inhibited the proliferation, migration and promoted apoptosis of LA795 cells, and eliminated the acute toxicity through sustained release from the hydrogel. Combined the antitumor performance of the limonin and sustained release of pec-CHO/CMC-AH hydrogel, this limonin/hydrogel system achieved satisfactory antitumor effect and eliminated side effects in vivo. Therefore, this system has great potential application for enhanced lung adenocarcinoma therapy.

Topics: Adenocarcinoma of Lung; Animals; Carboxymethylcellulose Sodium; Cellulose; Delayed-Action Preparations; Humans; Hydrogels; Limonins; Lung Neoplasms; Mice; Pectins

To examine the anti-metastatic activities of polysaccharides in broccoli, purified polysaccharides (BCE-I, -II, and -III) were isolated by fractionation of broccoli enzyme extracts and subsequent ethanol precipitation. BCE-I mainly consisted of galactose and arabinose, whereas BCE-II mainly consisted of galacturonic acid and rhamnose, and BCE-III mainly consisted of rhamnose and galactose. Of the three fractions, stimulation of murine peritoneal macrophages by BCE-I showed the greatest enhancement of tumor necrosis factor-α, interleukin (IL)-12, and IL-6 secretion. In addition, intravenous (i.v.) administration of BCE-I enhanced the lethal activity of natural killer (NK) cells on YAC-1 tumor cells significantly and dose-dependently in an

Topics: Animals; Antineoplastic Agents, Phytogenic; Brassica; Colonic Neoplasms; Female; Humans; Immunity, Innate; Interleukin-12; Interleukin-6; Killer Cells, Natural; Lung Neoplasms; Macrophage Activation; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Pectins; Plant Extracts; Polysaccharides

Pectin-guar gum-zinc oxide (PEC-GG-ZnO) nanocomposite was prepared by precipitation technique. The composite was characterized by using FT-IR, XRD, HRTEM, SAED, EDS, and SEM. TEM images showed the hexagonal shape of nanocomposite with the size range of 50-70 nm. Further, PEC-GG-ZnO was used as an immunomodulator for the first time to improve the cancer cells killing capabilities of human peripheral-blood lymphocytes (PBL). The lymphocyte proliferation assay proved the immunostimulatory property of the PEC-GG-ZnO which increased with the increase in concentration (25 μg/ml to 200 μg/ml). ELISA detection confirmed a significant increase in the release of IFN-γ, IL-2 and TNF-α cytokines and flow cytometry analysis revealed enhanced expression of CD3, CD8, and CD56 after treating PBL with PEC-GG-ZnO as compared to PEC and GG treatment. Moreover, we also found that nanocomposite pretreated human PBL displayed enhanced cytotoxicity towards lung (A549) and breast carcinoma (MCF-7) cells as compared to untreated PBL. The microcytotoxicity assay also demonstrated that with increase in effector: target ratios from 2.5:1 to 20:1, there was an increase in the cancer cell death. Taken together, the current data corroborates the immunostimulatory activities of PEC-GG-ZnO, a novel nanocomposite, hence it can serve as a promising cancer therapeutic agent.

Topics: Adjuvants, Immunologic; Breast Neoplasms; Cells, Cultured; Galactans; Humans; Lung Neoplasms; Lymphocytes; Mannans; MCF-7 Cells; Nanocomposites; Pectins; Plant Gums; Zinc Oxide

A water-soluble pectic polysaccharide HCA4S1 was isolated from Houttuynia cordata and purified by DEAE Cellulose and Sephacryl S-300 column. HCA4S1 with an average molecular weight of 21.7 kDa mainly consisted of rhamnose, galacturonic acid, galactose, and arabinose. By using partial acid hydrolysis, methylation analysis, and NMR spectra, the structure of this polysaccharide is found to have a backbone consisting of 1,4-linked α‑d‑GalA and 1,2,4-linked α‑l‑Rha. The latter was substituted at C-4 position by 1,4 linked, 1,6-linked β‑Galp, or Teminal linked β‑Gal. Bioactivity test showed that this polysaccharide might inhibit the proliferation of A549 lung cancer cell by inducing cell cycle arrest and apoptosis. The expression of cleaved caspase 3 and cyclinB1 was observed to be upregulated after the treatment with this polysaccharide. Collectively, these results suggest that the pectin HCA4S1 from Houttuynia cordata is of potential value in the treatment of lung cancer, though the underlying mechanisms remain to be further confirmed.

Topics: A549 Cells; Apoptosis; Carbohydrate Conformation; Caspase 3; Cell Cycle Checkpoints; Houttuynia; Humans; Lung Neoplasms; Neoplasm Proteins; Pectins

The aim of this work was to prepare pectin-poly (vinyl pyrrolidone) [PVP] based curcumin particulates to enhance the anticancer potential of curcumin, solubility and allow its localized controlled release. Pectin-PVP based curcumin particulates (PECTIN-PVP CUR) were prepared by spray drying technique in different ratios and were evaluated for surface morphology, micromeritics, flowability, particle size, drug content, in vitro dissolution, inhalable fraction, anti-angiogenesis/angiolysis and cytotoxicity. Results of micromeritic properties, Carr's index, Hausner's ratio and angle of repose were satisfactory. The batch CP3 was considered as optimum, due to excellent flowability, acceptable aggregation and enhanced solubility. The particle size and size distribution data of selected batch CP3 showed 90% of curcumin particulates having size less than 2.74μm, which may deposit to lungs. Twin Impinger studies showed that 29% of respirable fraction was generated, which could be directly delivered to lungs. The in vitro dissolution data showed many fold increase in dissolution rate. Angiolytic activity and MTT assay of PECTIN-PVP CUR have demonstrated enhancement in the anti-tumor potential, compared to curcumin alone. Altogether, PECTIN-PVP CUR were found suitable for local delivery and enhance its anticancer potential of curcumin.

Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Curcumin; Drug Carriers; Humans; Lung Neoplasms; Particle Size; Pectins; Povidone; Solubility

The aim of this study was to characterize a polysaccharide found in citrus peels with an anti-metastatic property. CPE-II was purified by the pectinase digestion of citrus peels. During in vivo lung metastasis of Colon26-M3.1, administration of 10μg of CPE-II per mouse showed 81.3% inhibition of metastasis. CPE-II consists of 15 different monosaccharides and 22 different glycosyl linkages, characteristic of rhamnogalacturonan II (RG-II). The primary structure was elucidated based on sugar composition, methylation analysis, oligosaccharide analysis, and sequencing using GC, GC-MS, LC-MS, and ESI-MS/MS analyses. Sequential degradation using partial acid hydrolysis indicated that CPE-II contained Rhap-(1→5)-Kdo, Araf-(1→5)-Dha, an AceA-containing nonasaccharide, and an uronic acid-rich oligosaccharide in addition to an α-(1→4)-galacturono-oligosaccharide main chain. The molecular weight of CPE-II was observed to decrease from 9 to 5kDa at a pH value of <2.0, as observed by HPSEC. Thus, we propose that the anti-metastatic CPE-II is primarily present as an RG-II dimer.

Topics: Animals; Antineoplastic Agents, Phytogenic; Carbohydrate Conformation; Cell Line, Tumor; Citrus; Colonic Neoplasms; Female; Fruit; Lung Neoplasms; Mice, Inbred BALB C; Neoplasm Transplantation; Pectins; Polygalacturonase

Melanoma is a malignant neoplasm of major concern because of its high mortality rate and failure of chemotherapy. Previously we have shown that galectin-3, a galactose specific lectin, plays a pivotal role in the initiation of metastasis. It was hypothesized that blocking galectin-3 with galactose rich dietary pectic polymer would inhibit metastasis. The current study analyzes the preventive effect and mode of action of a pectic polymer from Swallow Root (Decalepis hamiltonii) in a preventative study of B16F10 cells lung colonization. Matrix metalloproteinase (MMPs) activity was assayed by zymography. Apoptotic/proliferative markers and cytokines were analyzed by immunoassay. Results indicated ~88% inhibition of lung colonization by SRPP as compared to 60% by CPP and only 7% by GRPP. Further molecular analysis revealed that galectin-3 blockade was associated with down regulation of MMPs and NFκB. Activation of caspases supported the apoptotic effect of SRPP. Infiltration of inflammatory cells into the lung was evidenced by presence of CD11b

Topics: Animals; Antineoplastic Agents; Apocynaceae; Apoptosis; Biomarkers, Tumor; Cell Adhesion; Cell Division; Citrus; Diet; Drug Screening Assays, Antitumor; Galectin 3; Immunologic Factors; Lung Neoplasms; Melanins; Melanoma, Experimental; Mice; Neoplasm Invasiveness; Neoplasm Proteins; Oxidative Stress; Pectins; Zingiber officinale

To investigate the antitumor and antimetastatic polysaccharide from the mature leaves of green tea, GTE-II was purified using size exclusion chromatography. GTE-II consisted of 15 different sugars including rarely observed sugars such as 2-O-methyl-fucose, 2-O-methyl-xylose, apiose, aceric acid, 3-deoxy-d-manno-2-octulosonic acid, and 3-deoxy-d-lyxo-2-heptulosaric acid, which were characteristics of pectic polysaccharide rhamnogalacturonan-II. Treatment of peritoneal macrophages with GTE-II not only increased interleukin (IL)-6 and IL-12 production, but also had significantly increased tumoricidal activity against Yac-1 tumor cells than those obtained from untreated mice. In an assay of natural killer (NK) cell activity, intravenous administration of GTE-II significantly stimulated NK cytotoxicity against Yac-1 tumor cells. Furthermore, the depletion of NK cells by injection of rabbit anti-asialo GM1 serum eliminated the inhibitory effect of GTE-II on B16BL6 melanoma cells. These data suggest that GTE-II inhibits tumor metastasis, and its antitumor effect is associated with activation of macrophages and NK cells.

Topics: Animals; Antineoplastic Agents; Female; Glycosylation; Killer Cells, Natural; Lung Neoplasms; Macrophage Activation; Melanoma, Experimental; Methylation; Mice; Neoplasm Metastasis; Pectins; Plant Leaves; Polygalacturonase; Tea

A polysaccharide fraction, HBE-III, was successfully purified in a high yield (40.4%) from its crude polysaccharide (HBE-0) which was prepared from pectinase hydrolysates of the peels of the Korean Citrus Hallabong. In experimental lung metastasis studies of Colon 26-M3.1 carcinoma cells, prophylactic administration of HBE-III significantly inhibited lung metastasis in a dose-dependent manner. In an in vitro cytotoxicity analysis, HBE-III (up to 1000 μg/mL) did not affect the growth of Colon 26-M3.1 cells and normal cells. HBE-III enhanced production of IL-6 and IL-12 by murine peritoneal macrophages. In an assay for natural killer (NK) cell activity, HBE-III (1000 μg/mouse, i.v.) significantly augmented NK cytotoxicity against Yac-1 tumor cells. The depletion of NK cells by injection of mouse anti-asialo GM1 serum abolished the inhibitory effect of HBE-III on lung metastasis of Colon 26-M3.1 cells. These data suggest that HBE-III may inhibit tumor metastasis via activation of macrophages and NK cells.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Line; Cell Line, Tumor; Citrus; Colon; Colonic Neoplasms; Female; Hydrolysis; Interleukin-12; Interleukin-6; Killer Cells, Natural; Lung; Lung Neoplasms; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Pectins; Polysaccharides

In this report, we challenge a common perception that tumor embolism is a size-limited event of mechanical arrest, occurring in the first capillary bed encountered by blood-borne metastatic cells. We tested the hypothesis that mechanical entrapment alone, in the absence of tumor cell adhesion to blood vessel walls, is not sufficient for metastatic cell arrest in target organ microvasculature. The in vivo metastatic deposit formation assay was used to assess the number and location of fluorescently labeled tumor cells lodged in selected organs and tissues following intravenous inoculation. We report that a significant fraction of breast and prostate cancer cells escapes arrest in a lung capillary bed and lodges successfully in other organs and tissues. Monoclonal antibodies and carbohydrate-based compounds (anti-Thomsen-Friedenreich antigen antibody, anti-galectin-3 antibody, modified citrus pectin, and lactulosyl-l-leucine), targeting specifically beta-galactoside-mediated tumor-endothelial cell adhesive interactions, inhibited by >90% the in vivo formation of breast and prostate carcinoma metastatic deposits in mouse lung and bones. Our results indicate that metastatic cell arrest in target organ microvessels is not a consequence of mechanical trapping, but is supported predominantly by intercellular adhesive interactions mediated by cancer-associated Thomsen-Friedenreich glycoantigen and beta-galactoside-binding lectin galectin-3. Efficient blocking of beta-galactoside-mediated adhesion precludes malignant cell lodging in target organs.

Topics: Animals; Antibodies; Antibodies, Monoclonal; Bone Neoplasms; Breast Neoplasms; Cell Adhesion; Cell Line, Tumor; Citrus; Female; Galectin 3; Humans; Leucine; Lung Neoplasms; Male; Mice; Mice, Inbred ICR; Mice, SCID; Neoplasm Metastasis; Neoplasm Transplantation; Pectins; Prostatic Neoplasms

Topics: Animals; Disease Progression; Humans; Incidence; Lung Neoplasms; Male; Pectins; Prostatic Neoplasms

Studies have shown that the galactoside-containing simple sugars and anti-galactoside-binding lectin antibodies may affect experimental tumor cell metastasis. However, the limited number of reagents used thus far necessitate further observations.. Natural citrus pectin (CP) and pH-modified CP (MCP), rich in galactose residues, were used to study the involvement of carbohydrates containing galactoside residues in cellular interaction in vitro and in lung colonization in vivo of B16-F1 melanoma cells.. B16-F1 melanoma cells were incubated with various concentrations of CP and MCP. Their ability to form homotypic aggregation in vitro and tumor lung colonization in vivo in 8-week-old female C57BL/6 mice was then analyzed.. The CP binds to the surface of B16-F1 melanoma cells; this binding can be inhibited by lactose at a concentration of 0.15 M. Intravenous injection of the murine B16-F1 melanoma cells with the natural CP resulted in a significant increase (up to threefold) in the appearance of tumor colonies in the lung and in increased homotypic aggregation properties of the cells, while injection of MCP significantly decreased B16-F1 experimental metastasis (greater than 90%).. Tumor galactoside-binding proteins mediate cellular recognition by linking oligosaccharides with terminal D-galactoside residues on adjacent cells. Successful interference with such a process with MCP may lead to a reduced ability to form tumor cell emboli and metastasis.. These findings imply that the galactose-containing carbohydrate side chains of CP might mimic or compete with the natural ligand(s) of the tumor galactoside-binding protein (gal-lectin) and thus affect cellular interactions relevant for metastasis.

Topics: Animals; Cell Aggregation; Female; Lung Neoplasms; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Pectins; Tumor Cells, Cultured