Volume 6 Special Issue 2 2012
Medicinal Plants and Cancer Research

ISBN 978-4-907060-06-0

How to reference: Massa S, Franconi R (2012) Plant Genes and Plant Proteins as Adjuvants in Cancer Vaccination. In: Egamberdieva D, Tiezzi A (Eds) Medicinal Plants and Cancer Research. Medicinal and Aromatic Plant Science and Biotechnology 6 (Special Issue 2), 1-9

Guest Editors

Dilfuza Egamberdieva, Antonio Tiezzi

CONTENTS AND ABSTRACTS

Silvia Massa, Rosella Franconi (Italy) Plant Genes and Plant Proteins as Adjuvants in Cancer Vaccination (pp 1-9)

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Invited Review: The use of plant products as anti-microbial and immunostimulants has a traditional history and has contributed to the development of important therapeutic drugs used in modern medicine. The anti-cancer properties demonstrated so far by some plant-derived immunostimulants rely on the modulation of non-specific immune responses and do not directly affect immune memory cells. However, it should not be unexpected to find some plant-derived components being able to stimulate antigen-specific cell-mediated immunity in the context of vaccines. The identification of novel adjuvants would give further potential to the development of improved therapeutic anti-cancer vaccines, able to promote better presentation or immunogenicity of tumour antigens and to improve trafficking of effector T-cell populations to non-inflamed tumour sites. Among plant products with effects on microbes and immunity, beside many small secondary metabolites, there are also proteins and peptides and most of them are involved in the plant defence against pathogens and invading organisms. We will present data from our work on the use of plant compounds (as extracts, proteins or DNA sequences) as sources of innovative immunostimulants in the context of therapeutic vaccination of Human Papilloma Virus (HPV)-associated tumours. Further studies are required to determine the mechanism of action by which plant extracts and their active compounds (including secondary metabolites, proteins and peptides) exert their anti-cancer and adjuvant activity for their exploitation in therapeutic vaccines. Moreover, new in vivo and in vitro approaches to isolate novel adjuvant activities are needed.

Mohamed L. Ashour, Sherif S. Ebada (Egypt) Plant Natural Products as Potential Modulators of the Transcription Factor NF-κB (pp 10-19)

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Invited Review: Nuclear factor-κB (NF-κB) is an inducible transcription factor which plays important role in the regulation of the immune, inflammatory and carcinogenic responses. Partial NF-κB activation is necessary for normal cell survival and immunity; however the deregulated NF-κB expression is associated with cancer development, metastasis, and in several inflammatory disorders with a resistant phenotype and poor prognosis. Therefore, NF-κB has become an interesting target for drug discovery and several natural and synthetic products have been screened for their ability to inhibit NF-κB pathway. This review surveys the plant natural products with significant NF-κB inhibitory activity focusing on their potential mechanism of action and their implications for cancer therapy.

Luigi Lucini, Marco Pellizzoni, Gian Pietro Molinari, Fabrizio Franchi (Italy) Aloe Anthraquinones against Cancer (pp 20-24)

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Invited Mini-Review: Aloe has long been used in folk medicine for its curative and therapeutic properties, and two main classes of active compounds have been identified, namely anthraquinones and some characteristic β-polysaccharides. Among anthraquinones, aloe-emodin is reported to show the most interesting anticancer properties. This compound has been successfully tested against neuroectodermal cancer, leukemia, Merkel cell carcinoma and lung squamous cell carcinoma. Besides the effect on antioxidant enzymes is documented, several authors have identified the induction of cell apoptosis as the main mechanism through which aloe-emodin exerts its cytotoxic activity. In detail, the induction of apoptosis by aloe-emodin was related to the activation of caspases cleaves, and then activating downstream caspases.

Maria Pia Fuggetta, Andrea Cottarelli, Giulia Lanzilli, Maria Tricarico, Roberta Bernini (Italy) In Vitro Antitumor Activity of Olive Oil Tyrosol and Hydroxytyrosol and their Methyl Carbonate Derivatives (pp 25-30)

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Original Research Paper: A Mediterranean diet rich in olive oil has been associated with health benefits in humans. The phenolic compounds found in virgin olive oil have demonstrated antitumor activity and antioxidant properties. The aim of this study was to confirm the in vitro antiproliferative effect of tyrosol (TYR) and hydroxytyrosol (HTYR) on human cancer cell line and to investigate and compare the antitumor effect of methyl carbonate derivatives of these natural compounds as tyrosol methyl carbonate (TYRMC) and hydroxytyrosol methyl carbonate (HTYRMC) synthesized in our laboratory by an eco-friendly procedure. Four human tumor cell lines of melanoma (M14), pulmonary (H125), colon (WiDr) and promyelocytic leukaemia (HL60) were growth in the presence of 3.125, 6.25 12.5, 25, 50 and 100 mcg/ml of TYR, HTYR, TYRMC and HTYRMC for 24, 48 and 72 h. The antiproliferative activity was assayed by counting the cells in trypan blue, the apoptosis induction and cell cycle profiles were evaluated by flow cytometry analysis. A significant growth inhibition was observed in each tumour cell line exposed to these molecules in the experimental conditions described above. In addition this study demonstrated that HTYRMC results more effective in cell growth inhibition and apoptosis induction reaching 98.2% at the concentration of 100 mcg/ml. However, further studies are necessary to better understand the mechanisms of these molecules on tumour cell growth.

Donatella Ceccarelli, Elisa Ovidi, Doriana Triggiani, Carlo F. Morelli, Giovanna Speranza, AnnaRita Taddei, Antonio Tiezzi (Italy) Antiproliferative Activity of Aloe arborescens Leaf Skin Extracts Tested on Murine Myeloma Cells: Cytological Studies and Chemical Investigations (pp 31-36)

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Original Research Paper: MTT assays showed an intense antiproliferative activity (80%) of Aloe arborescens leaf skin extracts tested on murine myeloma cells. Bioassay-guided fractionation carried out by TLC allowed the identification of a spot showing antiproliferative activity; HPLC and NMR investigations showed that the TLC spot consisted of aloenin A and aloins A and B. The effects of the leaf extract and of the TLC spot were evaluated both by immunofluorescence techniques in order to test the microtubular array and at the morphological level by SEM and TEM observations.

Doriana Triggiani, Donatella Ceccarelli, Maria Grazia Cusi, Alessandro Paffetti, Daniela Braconi, Lia Millucci, Giulia Bernardini, Annalisa Santucci (Italy) Rubus ulmifolius Leaf Extract Inhibits Proliferation of Murine Myeloma Cells (pp 37-41)

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Original Research Paper: In the present paper we report preliminary results on the antiproliferative activity of Rubus ulmifolius leaf extract against murine myeloma cells (P3X63-Ag8.653). Cytotoxic effects of plant extract (range 3-30 μL/mL of cell culture) were evaluated by microscopy analyses and viability assays, revealing a clear dose-response relationship for cytotoxicity in treated cells vs. controls. The number of viable cells was reduced to nearly 30% when plant extract was tested at 3 μL/mL, and to nearly 3% when plant extract was tested at 5 μL/mL. Higher concentrations of plant extract allowed the detection of a very limited number of viable cells. Furthermore, the effects of R. ulmifolius leaf extract at the molecular level were investigated through a comparative proteomic approach, which allowed us to highlight how it might modulate protein expression in murine myeloma cells. In particular, only one protein spot was found under-expressed, whereas 44 protein spots showed significantly higher levels in plant extract-treated cells when compared to control cells. Our results may thus lay the basis and open new perspectives for future investigations of the effects of plant extracts in mammalian cells.

Ganesh Chandra Jagetia, V. A. Venkatesha (India) Preclinical Determination of the Anticancer Activity of Rohituka (Aphanamixis polystachya)in Ehrlich Ascites Tumor-Bearing Mice (pp 42-51)

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Original Research Paper: Anticancer activity of various doses of alcoholic extract of rohituka, Aphanamixis polystachya (APE) was studied in mice transplanted with Ehrlich ascites carcinoma (EAC). Administration of 0, 0.125, 0.25, 0.5, 0.75, 1, 1.25 or 1.5 g/Kg body weight APE once daily for consecutive 9 days resulted in a dose dependent regression in the tumor mass and increase in tumor-free survivors. The greatest anticancer activity was observed for 1 g/Kg APE as is evident by a maximum number of tumor-free survivors by 120 days post APE administration. Administrations of split dose of 0.5 g/Kg APE twice daily for nine consecutive days resulted in a greater number of tumor free-survivors than the single administration of 1 g/Kg APE concomitantly or 1 mg/Kg doxorubicin (positive control). The stage specific evaluation revealed that APE treatment was effective in regressing the tumors at all the stages and the most pronounced effect was observed up to stage III that lessened when the APE was administered during late stages of tumor development. Biochemical estimation revealed that APE administration increased lipid peroxidation by two folds accompanied by a two-fold decline in the glutathione contents at 8 h post-APE treatment. Similarly, APE treatment reduced the activities of glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, and catalase at 8 h by 2.1, 2.3, 2, and 3.5 folds, respectively. Our study indicates that APE treatment caused a dose dependent retardation in the tumor mass and regressed tumors even in the late stages of tumor development, which may be due to increased lipid peroxidation and reduction in the activities of antioxidant enzymes.

Ganesh Chandra Jagetia, Vijayashree Nayak (India) Indian Medicinal Herb Guduchi (Tinospora cordifolia Meirs) Exerts its Radiosensitizing Activity by Accelerating Chromosome Damage in HeLa Cells Exposed to Different Doses of γ-Radiation (pp 52-62)

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Original Research Paper: Radiotherapy is an important treatment modality and screening of phytoceuticals may enhance the clinical outcome of radiotherapy, therefore radiosensitzing activity of various guduchi (Tinospora cordifolia) extracts was studied in HeLa cells. Chromosomal aberrations were scored in HeLa cells treated with 10 µg/ml of aqueous, methanol, or methylene chloride guduchi extracts or doxorubicin before exposure to 0, 0.5, 1, 2 or 3 Gy of γ-radiation at 12, 24, 36 or 48 h post-irradiation. Irradiation of HeLa cells caused a dose dependent rise in the chromatid breaks, chromosome breaks, dicentric, centric rings, acentric fragments and total aberrations at all post-irradiation times and the dose response was linear quadratic for all types of aberrations scored. Chromatid breaks increased up to 12 h post-irradiation and declined steadily up to 48 h post-irradiation, whereas chromosome breaks, dicentric, acentric fragments and total aberrations elevated up to 24 h post-irradiation and declined thereafter. However, centric rings continued to rise steadily up to 48 h post-irradiation. Treatment of HeLa cells with aqueous, methanol or methylene chloride guduchi extract or doxorubicin before irradiation significantly enhanced various types of chromosomal aberrations and a maximum rise in the chromosome aberrations was observed in the HeLa cells treated with methylene chloride extract before irradiation when compared to other groups. Various guduchi extracts enhanced the effect of radiation in HeLa cells by increasing the molecular damage to cellular genome and their effect was similar to or even greater than doxorubicin (positive control) pretreatment, depending on the type of guduchi extract used.

Cigdem Kahraman, Zeliha S. Akdemir, I. Irem Tatli (Turkey) Promising Cytotoxic Activity Profile, Biological Activities and Phytochemical Screening of Verbascum L. Species (pp 63-75)

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Invited Review: Verbascum species, the largest genus of the family Scrophulariaceae, have been used in traditional medicines for centuries in almost all parts of the world. In this paper, the usage, biological activities (antioxidant, anticholinesterase, antiinflammatory, antinociceptive, wound healing, cytotoxic, anticancer, antitumor, immunomodulatory, antimicrobial, antimalarial, anthelmintic, antiviral, antitussive, anti-ulserogenic, hepatoprotective, antihyperlipidemic, pesticidal, antigermination and the other activities), chemical constituents of these species and new species of the genus are reviewed.