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Pharmaceuticals (Basel, Switzerland) Jul 2021The presence of small subpopulations of cells within tumor cells are known as cancer stem cells (CSCs). These cells have been the reason for metastasis, resistance with... (Review)
Review
The presence of small subpopulations of cells within tumor cells are known as cancer stem cells (CSCs). These cells have been the reason for metastasis, resistance with chemotherapy or radiotherapy, and tumor relapse in several types of cancers. CSCs underwent to epithelial-mesenchymal transition (EMT) and resulted in the development of aggressive tumors. CSCs have potential to modulate numerous signaling pathways including Wnt, Hh, and Notch, therefore increasing the stem-like characteristics of cancer cells. The raised expression of drug efflux pump and suppression of apoptosis has shown increased resistance with anti-cancer drugs. Among many agents which were shown to modulate these, the plant-derived bioactive agents appear to modulate these key regulators and were shown to remove CSCs. This review aims to comprehensively scrutinize the preclinical and clinical studies demonstrating the effects of phytocompounds on CSCs isolated from various tumors. Based on the available convincing literature from preclinical studies, with some clinical data, it is apparent that selective targeting of CSCs with plants, plant preparations, and plant-derived bioactive compounds, termed phytochemicals, may be a promising strategy for the treatment of relapsed cancers.
PubMed: 34358102
DOI: 10.3390/ph14070676 -
Biomedicine & Pharmacotherapy =... Dec 2023The aggressive and incurable diffuse gliomas constitute 80% of malignant brain tumors, and patients succumb to recurrent surgeries and drug resistance. Epidemiological...
The aggressive and incurable diffuse gliomas constitute 80% of malignant brain tumors, and patients succumb to recurrent surgeries and drug resistance. Epidemiological research indicates that substantial consumption of fruits and vegetables diminishes the risk of developing this tumor type. Broccoli consumption has shown beneficial effects in both cancer and neurodegenerative diseases. These effects are partially attributed to the isothiocyanate sulforaphane (SFN), which can regulate the Keap1/Nrf2/ARE signaling pathway, stimulate detoxifying enzymes, and activate cellular antioxidant defense processes. This study employs a C6 rat glioma model to assess the chemoprotective potential of aqueous extracts from broccoli seeds, sprouts, and inflorescences, all rich in SFN, and pure SFN as positive control. The findings reveal that administering a dose of 100 mg/kg of broccoli sprout aqueous extract and 0.1 mg/kg of SFN to animals for 30 days before introducing 1 × 10 cells effectively halts tumor growth and progression. This study underscores the significance of exploring foods abundant in bioactive compounds, such as derivatives of broccoli, for potential preventive integration into daily diets. Using broccoli sprouts as a natural defense against cancer development might seem idealistic, yet this investigation establishes that administering this extract proves to be a valuable approach in designing strategies for glioma prevention. Although the findings stem from a rat glioma model, they offer promising insights for subsequent preclinical and clinical research endeavors.
Topics: Humans; Rats; Animals; Brassica; Kelch-Like ECH-Associated Protein 1; Plant Extracts; NF-E2-Related Factor 2; Isothiocyanates; Glioma
PubMed: 37839110
DOI: 10.1016/j.biopha.2023.115720 -
International Journal of Nanomedicine 2023Tumors are the second-most common disease in the world, killing people at an alarming rate. As issues with drug resistance, lack of targeting, and severe side effects... (Review)
Review
Tumors are the second-most common disease in the world, killing people at an alarming rate. As issues with drug resistance, lack of targeting, and severe side effects are revealed, there is a growing demand for precision-targeted drug delivery systems. Plant-derived nanovesicles (PDNVs), which arecomposed of proteins, lipids, RNA, and metabolites, are widely distributed and readily accessible. The potential for anti-proliferative, pro-apoptotic, and drug-resistant-reversing effects on tumor cells, as well as the ability to alter the tumor microenvironment (TME) by modulating tumor-specific immune cells, make PDNVs promising anti-tumor therapeutics. With a lipid bilayer structure that allows drug loading and a transmembrane capacity readily endocytosed by cells, PDNVs are also expected to become a new drug delivery platform. Exogenous modifications of PDNVs enhance their circulating stability, tumor targeting ability, high cell endocytosis rate, and controlled-release capacity. In this review, we summarize PDNVs' natural antitumor activity, as well as engineered PDNVs as efficient precision-targeted drug delivery tools that enhance therapeutic effects. Additionally, we discuss critical considerations related to the issues raised in this area, which will encourage researchers to improve PDNVs as better anti-tumor therapeutics for clinic applications.
Topics: Humans; Delayed-Action Preparations; Drug Delivery Systems; Drug-Related Side Effects and Adverse Reactions; Drug Liberation; Endocytosis
PubMed: 37635909
DOI: 10.2147/IJN.S413831 -
Molecular Phylogenetics and Evolution Apr 2022Tumor-inducing (Ti) and root-inducing (Ri) plasmids of Agrobacterium that display a large diversity are involved in crown gall and hairy root plant diseases. Their...
Tumor-inducing (Ti) and root-inducing (Ri) plasmids of Agrobacterium that display a large diversity are involved in crown gall and hairy root plant diseases. Their phylogenetic relationships were inferred from an exhaustive set of Ti and Ri plasmids (including 36 new complete Ti plasmids) by focusing on T-DNA and virulence regions. The opine synthase gene content of T-DNAs revealed 13 opine types corresponding to former classifications based on opines detected in diseased plants, while the T-DNA gene content more finely separate opine types in 18 T-DNA organizations. This classification was supported by the phylogeny of T-DNA oncogenes of Ti plasmids. The five gene organizations found in Ti/Ri vir regions was supported by the phylogeny of common vir genes. The vir organization was found to be likely an ancestral plasmid trait separating "classic" Ti plasmids (with one or two T-DNAs) and "Ri and vine-Ti" plasmids. A scenario generally supported by the repABC phylogeny. T-DNAs likely evolved later with the acquisition of opine characteristics as last steps in the Ti/Ri plasmid evolution. This novel evolutionary classification of Ti/Ri plasmids was found to be relevant for accurate crown gall and hairy root epidemiology.
Topics: DNA, Bacterial; Humans; Neoplasms; Phylogeny; Plant Tumors; Plasmids; Rhizobium; Virulence
PubMed: 35017066
DOI: 10.1016/j.ympev.2022.107388 -
International Journal of Molecular... Jun 2021Breast cancer (BC) is a leading cause of cancer deaths in women in less developed countries and the second leading cause of cancer death in women in the U.S. In this...
Breast cancer (BC) is a leading cause of cancer deaths in women in less developed countries and the second leading cause of cancer death in women in the U.S. In this study, we report the inhibition of E2-mediated mammary tumorigenesis by (cumin) administered via the diet as cumin powder, as well as dried ethanolic extract. Groups of female ACI rats were given either an AIN-93M diet or a diet supplemented with cumin powder (5% and 7.5%, /) or dried ethanolic cumin extract (1%, /), and then challenged with subcutaneous E2 silastic implants (1.2 cm; 9 mg). The first appearance of a palpable mammary tumor was significantly delayed by both the cumin powder and extract. At the end of the study, the tumor incidence was 96% in the control group, whereas only 55% and 45% animals had palpable tumors in the cumin powder and extract groups, respectively. Significant reductions in tumor volume (660 ± 122 vs. 138 ± 49 and 75 ± 46 mm) and tumor multiplicity (4.21 ± 0.43 vs. 1.16 ± 0.26 and 0.9 ± 0.29 tumors/animal) were also observed by the cumin powder and cumin extract groups, respectively. The cumin powder diet intervention dose- and time-dependently offset E2-related pituitary growth, and reduced the levels of circulating prolactin and the levels of PCNA in the mammary tissues. Mechanistically, the cumin powder diet resulted in a significant reversal of E2-associated modulation in ERα, CYP1A1 and CYP1B1. Further, the cumin powder diet reversed the expression levels of miRNAs (miR-182, miR-375, miR-127 and miR-206) that were highly modulated by E2 treatment. We analyzed the composition of the extract by GC/MS and established cymene and cuminaldehyde as major components, and further detected no signs of gross or systemic toxicity. Thus, cumin bioactives can significantly delay and prevent E2-mediated mammary tumorigenesis in a safe and effective manner, and warrant continued efforts to develop these clinically translatable spice bioactives as chemopreventives and therapeutics against BC.
Topics: Animals; Cuminum; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP1B1; Estradiol; Estrogens; Female; Gene Expression Regulation, Neoplastic; Mammary Neoplasms, Experimental; MicroRNAs; Plant Extracts; Rats; Rats, Inbred ACI
PubMed: 34201250
DOI: 10.3390/ijms22126194 -
Journal of Ethnopharmacology Dec 2023The dried and mature seeds of Strychnons pierriana A.W.Hill. have been called Strychnine Semen(S. Semen). It have been used in traditional Chinese medicine for nearly... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
The dried and mature seeds of Strychnons pierriana A.W.Hill. have been called Strychnine Semen(S. Semen). It have been used in traditional Chinese medicine for nearly 400 years. In recent decades, scholars at home and abroad have widely used S. Semen in the treatment of tumor diseases, showing good anti-tumor effects. In this paper, the modern research achievements of S. Semen are reviewed, including traditional uses, phytochemistry, pharmacology, and toxicology.
AIM OF THE STUDY
In recent years, the research on S. Semen has increased gradually, especially the research on its anti-tumor. This paper not only reviewed the traditional uses, chemical constituents and pharmacological activities of S. Semen, but also comprehensively listed the mechanisms of Strychnos in the treatment of different tumors, providing a review for further research and development of Strychnos resources.
MATERIALS AND METHODS
A systematic review of the literature on Fuzi was performed using several resources, namely classic books on Chinese herbal medicine and various scientific databases, such as PubMed, the Web of Science, and the China Knowledge Resource Integrated databases.
RESULTS
The main constituents of S. Semen include alkaloids, terpenoids, steroids, and their glycosides. Modern studies have proved that S. Semen has a wide range of pharmacological effects, including anti-inflammatory and analgesic, anti-thrombotic, myocardial cell protection, immune regulation, nerve excitation, and anti-tumor effects. Among them, the anti-tumor effect has been the focus of research in recent years. S. Semen have a certain therapeutic effect on many kinds of tumors, such as liver cancer, colon cancer, and stomach cancer in the digestive system, breast, cervical, and ovarian cancer in the reproductive system, myeloma and leukemia in the blood system, and those in the nervous system and the immune system.
CONCLUSION
Strychnine has an inhibitory effect on a variety of tumors. However, modern studies of strychnine are incomplete, and more in-depth studies are needed on its stronger bioactive constituents and potential pharmacological effects. The antitumor effect of Strychnine is worth further exploration.
Topics: Strychnine; Seeds; Drugs, Chinese Herbal; Alkaloids; Medicine, Chinese Traditional; Analgesics; Phytochemicals; Ethnopharmacology; Plant Extracts
PubMed: 37348797
DOI: 10.1016/j.jep.2023.116748 -
Journal of Dietary Supplements 2023The goal of this study was to evaluate if combinations of ingredients with known anti-cachexia benefits (Fish oil-FO with either curcumin or Green tea extract-GTE), have...
The goal of this study was to evaluate if combinations of ingredients with known anti-cachexia benefits (Fish oil-FO with either curcumin or Green tea extract-GTE), have adverse effects on tumor growth, using human carcinoma xenograft mice models. FO (EPA/DHA 360 mg/kg bw), GTE (90 mg/kg bw), and curcumin (180 mg/kg bw) were administered orally, alone or in combination, to nude mice bearing either A549 human non-small cell lung carcinoma or SW620 human colon carcinoma tumors. Bodyweight, tumor growth, survival time, and other clinical endpoints were assessed. The ingredients either alone or in combinations were well tolerated in both lung and colon tumor-bearing mice. There were no significant group differences between individual or combination treatments for tumor growth (A549 or SW620) as measured by the median time in days to endpoint of tumor volume (TTE). TTE results indicate that these ingredients (alone or combinations) did not adversely impact tumor growth. No significant differences in body weights or survival were observed between controls and treatment groups indicating no adverse health effects of the ingredients. In conclusion, FO, GTE or curcumin administered as monotherapies and in combination were well tolerated and displayed no adverse effects on tumor growth in mouse xenograft models of lung and colon cancer.
Topics: Humans; Mice; Animals; Curcumin; Polyphenols; Fish Oils; Heterografts; Mice, Nude; Colonic Neoplasms; Lung; Carcinoma; Plant Oils
PubMed: 34983294
DOI: 10.1080/19390211.2021.2021344 -
Frontiers in Immunology 2023The low immunogenicity of tumor antigens and unacceptable toxicity of adjuvants has hindered the application and development of tumor vaccines. Hence, we designed a...
OBJECTIVES
The low immunogenicity of tumor antigens and unacceptable toxicity of adjuvants has hindered the application and development of tumor vaccines. Hence, we designed a novel anti-tumor vaccine composed of a plant-derived immunostimulant molecular nanoadjuvant (a self-nanoemulsifying system, SND) and the antigen OVA, to reinvigorate the immune response and inhibit tumor progression.
METHODS
In this study, this novel nanoadjuvant with Saponin D (SND) was designed and prepared by low-energy emulsification methods. Several important characteristics of the SND, including morphology, size, polymer dispersity index (PDI), zeta potential, and stability, were estimated, and the cytotoxicity of the SND was evaluated by MTT assay. Additionally, the immune response in terms of antibody titer levels and cellular immunity were evaluated after immunization with the vaccine, and the preventative and therapeutic effects of this novel vaccine against tumors were estimated. Finally, the antigen release profile was determined by IVIS imaging and by assay.
RESULTS
This SND nanoadjuvant had good characteristics including the average particle size of 26.35 ± 0.225 nm, narrow distribution of 0.221 ± 1.76, and stability zeta potential of -12.9 ± 0.83 mV. And also, it had good stability (size, PDI, zeta potential, antigen stability) and low toxicity and , and delayed antigen release . The humoral immune response (IgG, IgG1, IgG2a, and IgG2b) and cellular immune level (cytokines of splenocytes including IFN-γ, IL-4, IL-1β andIL-17A) were both improved greatly after injected immunization at 0, 14, 28 days with the novel nanoadjuvant and antigen OVA. Importantly, this novel nanoadjuvant combined with OVA might lead to the induction of the prevent and treatment efficacy in the E.G7-OVA tumor-bearing mice.
CONCLUSIONS
These results suggested that this novel nanoadjuvant encapsulated natural plant immunostimulant molecular OPD could be a good candidate of tumor vaccine adjuvant for reinvigorating the immune response and powerfully inhibiting tumor growth effect.
Topics: Mice; Animals; Adjuvants, Immunologic; Neoplasms; Immunity, Humoral; Cancer Vaccines; Antigens, Neoplasm; Immunoglobulin G; Saponins
PubMed: 37415983
DOI: 10.3389/fimmu.2023.1154836 -
Biotechnology Advances 2021Molecular farming in plants is an emerging platform for the production of pharmaceutical proteins, and host species such as tobacco are now becoming competitive with... (Review)
Review
Molecular farming in plants is an emerging platform for the production of pharmaceutical proteins, and host species such as tobacco are now becoming competitive with commercially established production hosts based on bacteria and mammalian cell lines. The range of recombinant therapeutic proteins produced in plants includes replacement enzymes, vaccines and monoclonal antibodies (mAbs). But plants can also be used to manufacture toxins, such as the mistletoe lectin viscumin, providing an opportunity to express active antibody-toxin fusion proteins, so-called recombinant immunotoxins (RITs). Mammalian production systems are currently used to produce antibody-drug conjugates (ADCs), which require the separate expression and purification of each component followed by a complex and hazardous coupling procedure. In contrast, RITs made in plants are expressed in a single step and could therefore reduce production and purification costs. The costs can be reduced further if subcellular compartments that accumulate large quantities of the stable protein are identified and optimal plant growth conditions are selected. In this review, we first provide an overview of the current state of RIT production in plants before discussing the three key components of RITs in detail. The specificity-defining domain (often an antibody) binds cancer cells, including solid tumors and hematological malignancies. The toxin provides the means to kill target cells. Toxins from different species with different modes of action can be used for this purpose. Finally, the linker spaces the two other components to ensure they adopt a stable, functional conformation, and may also promote toxin release inside the cell. Given the diversity of these components, we extract broad principles that can be used as recommendations for the development of effective RITs. Future research should focus on such proteins to exploit the advantages of plants as efficient production platforms for targeted anti-cancer therapeutics.
Topics: Animals; Antibodies, Monoclonal; Immunotoxins; Recombinant Proteins; Nicotiana
PubMed: 33373687
DOI: 10.1016/j.biotechadv.2020.107683 -
Nano Letters Jul 2022We have previously shown the plant virus Cowpea mosaic virus (CPMV) to be an efficacious in situ cancer vaccine, providing elimination of tumors and tumor-specific...
We have previously shown the plant virus Cowpea mosaic virus (CPMV) to be an efficacious in situ cancer vaccine, providing elimination of tumors and tumor-specific immune memory. Additionally, we have shown that CPMV recruits Natural Killer (NK) cells within the tumor microenvironment. Here we aimed to determine whether a combination of CPMV and anti-4-1BB monoclonal antibody agonist to stimulate tumor-resident and CPMV-recruited NK cells is an effective dual therapy approach to improve NK cell function and in situ cancer vaccination efficacy. Using murine models of metastatic colon carcinomatosis and intradermal melanoma, intratumorally administered CPMV + anti-4-1BB dual therapy provided a robust antitumor response, improved elimination of primary tumors, and reduced mortality compared to CPMV and anti-4-1BB monotherapies. Additionally, on tumor rechallenge there was significant delay/prevention of tumor development and improved survival, highlighting that the CPMV + anti-4-1BB dual therapy enables potent and durable antitumor efficacy.
Topics: Animals; Comovirus; Humans; Killer Cells, Natural; Melanoma; Mice; Tumor Microenvironment; Vaccination
PubMed: 35713326
DOI: 10.1021/acs.nanolett.2c01328