Antitumor activity against murine lymphoma L5178Y model of proteins from cacao (Theobroma cacao L.) seeds in relation with in vitro antioxidant activity Ana M Preza1* María E Jaramillo1* , Ana M Puebla2* , Juan C Mateos3* , Rodolfo Hernández3* and Eugenia Lugo3
1 Departamento de Graduados e Investigación en Alimentos, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala S/N, Delegación Miguel Hidalgo, 06470 México, D.F., México
2 Laboratorio de Inmunofarmacología de Productos Naturales, Centro de Investigación Biomédica de Occidente, I.M.S.S., Sierra Mojada No. 800, Col. Independencia, 44340 Guadalajara, Jalisco, México
3 Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, A.C., Av. Normalistas 800, Colinas de la Normal, 44270 Guadalajara, Jalisco, México
Background Recently, proteins and peptides have become an added value to foodstuffs due to new knowledge about its structural analyses as related to antioxidant and anticancer activity. Our goal was to evaluate if protein fractions from cacao seeds show antitumor activity on lymphoma murine L5178Y model. The antioxidant activity of these fractions was also evaluated with the aim of finding a correlation with the antitumor activity.
Methods Differential extraction of proteins from unfermented and semi-fermented-dry cacao seeds was performed and characterized by SDS-PAGE and FPLC size-exclusion chromatography. Antitumor activity was evaluated against murine lymphoma L5178Y in BALB/c mice (6 × 104 cells i.p.), with a treatment oral dose of 25 mg/kg/day of each protein fraction, over a period of 15 days. Antioxidant activity was evaluated by the ABTS+ and ORAC-FL assays.
Results Albumin, globulin and glutelin fractions from both cacao seed type were obtained by differential solubility extraction. Glutelins were the predominant fraction. In the albumin fraction, polypeptides of 42.3 and 8.5 kDa were found in native conditions, presumably in the form of two peptide chains of 21.5 kDa each one. The globulin fraction presented polypeptides of 86 and 57 kDa in unfermented cacao seed that produced the specific-cacao aroma precursors, and after fermentation the polypeptides were of 45 and 39 kDa. The glutelin fraction presented proteins >200 kDa and globulins components <100 KDa in lesser proportion. Regarding the semifermented-dry cacao seed, it was observed that the albumin fraction showed antitumoral activity, since it caused significant decreases (p < 0.05) in the ascetic fluid volume and packed cell volume, inhibiting cell growth in 59.98 ± 13.6% at 60% of the population; while the greatest antioxidant capacity due to free radical scavenging capacity was showed by the albumin and glutelin fraction in both methods assayed.
Conclusion This study is the first report on the biological activity of semifermented-dry cacao protein fractions with their identification, supporting the traditional use of the plant. The albumin fraction showed antitumor and free radical scavenging capacity, however both activities were not correlated. The protein fractions could be considered as source of potential antitumor peptides.
Source: BMC Complementary and Alternative Medicine 2010, 10:61doi:10.1186/1472-6882-10-61 LINK TO FULL ARTICLE
Cinnamon extract induces tumor cell death through inhibition of NFκB and AP1
Background Cinnamomum cassia bark is the outer skin of an evergreen tall tree belonging to the family Lauraceae containing several active components such as essential oils (cinnamic aldehyde and cinnamyl aldehyde), tannin, mucus and carbohydrate. They have various biological functions including anti-oxidant, anti-microbial, anti-inflammation, anti-diabetic and anti-tumor activity. Previously, we have reported that anti-cancer effect of cinnamon extracts is associated with modulation of angiogenesis and effector function of CD8+ T cells. In this study, we further identified that anti-tumor effect of cinnamon extracts is also link with enhanced pro-apoptotic activity by inhibiting the activities NFκB and AP1 in mouse melanoma model.
Methods Water soluble cinnamon extract was obtained and quality of cinnamon extract was evaluated by HPLC (High Performance Liquid Chromatography) analysis. In this study, we tested anti-tumor activity and elucidated action mechanism of cinnamon extract using various types of tumor cell lines including lymphoma, melanoma, cervix cancer and colorectal cancer in vitro and in vivo mouse melanoma model.
Results Cinnamon extract strongly inhibited tumor cell proliferation in vitro and induced active cell death of tumor cells by up-regulating pro-apoptotic molecules while inhibiting NFκB and AP1 activity and their target genes such as Bcl-2, BcL-xL and survivin. Oral administration of cinnamon extract in melanoma transplantation model significantly inhibited tumor growth with the same mechanism of action observed in vitro.
Conclusion Our study suggests that anti-tumor effect of cinnamon extracts is directly linked with enhanced pro-apoptotic activity and inhibition of NFκB and AP1 activities and their target genes in vitro and in vivo mouse melanoma model. Hence, further elucidation of active components of cinnamon extract could lead to development of potent anti-tumor agent or complementary and alternative medicine for the treatment of diverse cancers.
Regulation of Caspase-3 and Bcl-2 Expression in Dalton's Lymphoma Ascites Cells by AbrinV. Ramnath,1 P. S. Rekha,1 G. Kuttan,2 and R. Kuttan31Department of Physiology, College of Veterinary and Animal Sciences, Kerala Agricultural University, Mannuthy, Thrissur, 680 651, Kerala, 2Department of Immunology and 3Amala Cancer Research Centre, Amala Nagar, Thrissur, 680 553, Kerala, IndiaFor reprints and all correspondence: Department of Physiology, College of Veterinary and Animal Sciences, Kerala Agricultural University, Mannuthy, Thrissur, 680 651, Kerala
Abstract The role of abrin, a toxic lectin isolated from seeds of Abrus precatorius Linn in inducing apoptosis in murine Dalton's Lymphoma Ascites (DLA) cells was evaluated. Abrin when incubated at the concentration of 10 ng per million DLA cells could bring about cell death as typical morphological changes with apoptosis. However, necrotic cell death dominated when a higher dose of abrin was used. DNA samples, isolated from DLA cells treated with abrin showed fragmentation. Abrin brought about induction of apoptosis by stimulating the expression of pro-apoptotic Caspase-3, at the same time blocking the expression of Bcl-2, which is an anti apoptotic gene. However, the expression of tumor suppressor gene p53 has not been observed in control and abrin-treated DLA cells. Results suggested that abrin effectively induced apoptotic changes in the tumor cells that led to cellular death.
Potent antitumor activity of Rubia cordifolia Parag R. Patel1*, Bhuvan P. Raval2, Hamsraj A. Karanth1, Vishal R. Patel3
1Parul Institute of Pharmacy, Limda, Vadodara, India 2K. J. College of Pharmacy,Vadasma-382708, North Gujarat, India Baroda college of Pharmacy, Limda, Vadodara, India
Abstract Background: Cancer is a leading cause of death. Rubia cordifolia is a traditional ayurvedic medicine being used as a remedy for various ailments.
Results: Dichloromethane fraction of Rubia cordifolia extract exhibited potent inhibition of human leukaemia cell line and human histolytic lymphoma cell line while was found to be lesser active against normal human kidney cells displaying safety for normal cells.
Conclusion: Study results show that root extracts of Rubia Cordifolia is promisingly cytotoxic and they might have antitumor activity against myeloid leukemia and Histolytic lymphoma. None of the fraction of the extract was found to be cytotoxic against the normal cell line (HEK293) in the given range of concentration. So, this plant extracts may have clinical and therapeutic proposition in the most life threaten disease like cancer and further studies are required to investigate this plant as source of antineoplastic agents
Seaweed extract may hold promise for non-Hodgkin's lymphoma treatment
DEAD SEA, Jordan — Seaweed extract may eventually emerge as a lymphoma treatment, according to laboratory research presented at the second AACR Dead Sea International Conference on Advances in Cancer Research: From the Laboratory to the Clinic, held here March 7-10, 2010.
Lymphoma is a cancer of the immune system and is classified into Hodgkin's and non-Hodgkin's types, which are then further classified into B-cell and T-cell groups.
"Some forms of B-cell lymphoma are especially resistant to standard treatment and thus new therapies are needed," said Mohammad Irhimeh, Ph.D., assistant professor of hematoncology and stem cells at the Hashemite University in Jordan. "In this study, we looked at a new treatment strategy using novel active compounds derived from a natural source ¬¬— seaweed."
Seaweeds containing fucoidan, a sulfated polysaccharide similar to heparin in chemical structure, have been reported to have anti-tumor activity in mice and some cell lines.
For the current study, Irhimeh and colleagues at the University of California, Berkeley, and Royal Hobart Hospital in Australia treated lymphoma cell lines with a commercially available seaweed extract.
They found that the extract had an inhibitory effect on the growth of lymphoma cell lines, while leaving the control healthy cells intact. The researchers also noted a significant pattern of activity in the genes known to be linked with apoptosis, or cell death, in lymphoma.
Irhimeh said they would continue to study the mechanism of action for these biological effects and had a goal of conducting phase II or III clinical trials.
Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues
Qi Chen,*† Michael Graham Espey,‡ Murali C. Krishna,‡ James B. Mitchell,‡ Christopher P. Corpe,* Garry R. Buettner,§ Emily Shacter,† and Mark Levine*¶*Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Free Radical and Radiation Biology Program, University of Iowa, Iowa City, IA 52242-1101; and †Laboratory of Biochemistry, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892
Abstract Human pharmacokinetics data indicate that i.v. ascorbic acid (ascorbate) in pharmacologic concentrations could have an unanticipated role in cancer treatment. Our goals here were to test whether ascorbate killed cancer cells selectively, and if so, to determine mechanisms, using clinically relevant conditions. Cell death in 10 cancer and 4 normal cell types was measured by using 1-h exposures. Normal cells were unaffected by 20 mM ascorbate, whereas 5 cancer lines had EC50 values of <4 mM, a concentration easily achievable i.v. Human lymphoma cells were studied in detail because of their sensitivity to ascorbate (EC50 of 0.5 mM) and suitability for addressing mechanisms. Extracellular but not intracellular ascorbate mediated cell death, which occurred by apoptosis and pyknosis/necrosis. Cell death was independent of metal chelators and absolutely dependent on H2O2 formation. Cell death from H2O2 added to cells was identical to that found when H2O2 was generated by ascorbate treatment. H2O2 generation was dependent on ascorbate concentration, incubation time, and the presence of 0.5-10% serum, and displayed a linear relationship with ascorbate radical formation. Although ascorbate addition to medium generated H2O2, ascorbate addition to blood generated no detectable H2O2 and only trace detectable ascorbate radical. Taken together, these data indicate that ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for formation of H2O2, and that blood can be a delivery system of the pro-drug to tissues. These findings give plausibility to i.v. ascorbic acid in cancer treatment, and have unexpected implications for treatment of infections where H2O2 may be beneficial.