Elderberry (Sambucus nigra) shows promise as a naturopathic treatment against melanoma in vivo and several elderberry fractions decrease melanoma and neuroblastoma cell proliferation in vitro

It is widely accepted that elderberry (Sambucus nigra) has many positive health benefits, some of which might slow the rate of cancer growth. The objective of this research is to identify active components of elderberry capable of modulating melanoma cell proliferation in both in vitro experiments and in an in vivo murine model. Melanoma is of interest because incidence of melanoma increases annually and treatment of melanoma is crucial before stages of metastasis. A diet including elderberry extracts may be a naturopathic strategy to slow melanoma growth in at-risk patients, including elderly and immune-suppressed individuals. In a murine model, groups of mice were given intraperitoneal injections of either sterile water (control) or sterile crude elderberry (treatment) before challenge by murine melanoma. 13 days following successful cancer cell challenge, mice were sacrificed and tumor size and weight were recorded. On average, control mice had larger tumors compared to treatment mice in both tumor size and weight. Also, two out of three control mouse tumors metastasized into the peritoneal cavity (whereas all treatment mouse tumors remained local), suggesting that crude elderberry may also decrease risk of tumor metastasis. Elderberry extracts were separated and purified. Human melanoma (MeWo) cells were supplemented with individual elderberry fractions to examine tumor suppressive activity by radioactive thymidine uptake assays. Several elderberry fractions showed in vitro evidence of decreased melanoma proliferation and were pooled based upon similar suppressive abilities. These pooled fractions suppressed human neuroblastoma (SH-545Y) and murine melanoma (B16 F10) growth in vitro, suggesting that pooled elderberry fractions are effective in suppressing multiple lines of cancers. I am currently preparing active pooled elderberry fractions to use in a similar murine model. Proper identification of melanoma-suppressing elderberry fractions may lead to diet-based strategies for natural suppression of melanoma.http://opus.ipfw.edu/stu_symp2013/1036/thumbnail.jp

Isolation and characterization of active elderberry fractions that inhibit melanoma growth in vitro and in vivo

The incidence rates of melanoma continue to rise annually despite recent progression in cancer treatments. Cancer is the most prevalent amongst elderly individuals, where immunosenescence has compromised some immune function, and therefore decreased certain tumor detection abilities. Current tumor removal strategies include radiation, chemotherapy and surgical excision: treatments that aim to lower cancer cells, but may also affect normal cells in the process. In the case of chemotherapy, which targets and kills rapidly dividing cells, many immune cells are lowered as a side effect, leaving many patients immune-suppressed and more susceptible to infection. There is a need for naturopathic treatments capable of decreasing tumor cell proliferation without compromising the body\u27s normal immune function. Extracts from elderberry (Sambucus nigra) may be able to satisfy this need. Previous reports suggest that phytochemicals, such as the ones present in elderberry, may stimulate the immune response by secretion of cytokines, provide antioxidant protection to prevent cellular damage, and inhibit tumor growth directly. Our primary goal was to separate the active components of elderberry and assess their inhibitory effects on the growth of multiple cancerous and transformed cell lines, as well as characterize their effects on stimulation of T lymphocyte proliferation and IL-2 secretion in vitro. Murine melanoma model experiments were also performed with crude elderberry and elderberry fractions to analyze the tumor-suppressive activity of elderberry treatments in vivo. Spleen cell proliferation and in vivo experiments were also performed with different aged groups of mice to uncover the tumor -inhibiting and immune-inducing effects of elderberry and active elderberry fractions on aged mice. Active elderberry fractions were then preliminarily identified. All separated elderberry fractions were able to significantly suppress the growth of B16-F10 murine melanoma and SH-SY5Y human neuroblastoma cells in vitro. Several separated fractions also inhibited growth of a human melanoma cell line, MeWo, and a transformed non-cancerous line, CHO-K1. When incubated with concanavalin A (Con A, a known mitogen) and spleen cells from a middle aged and old mouse, separated fractions of elderberry did not increase proliferation above the positive control (cells incubated with con A only) , however, they induced a larger proliferation response in the older mouse spleen cells. Three active fractions induced secretion of IL-2 from spleen cells above the positive control. In general, mice induced to produce tumors developed smaller, localized tumors when treated with crude elderberry compared to mice treated with water, whose tumors were larger and metastatic. The active elderberry fractions were too potent to be successfully implemented in an in vivo experiment, and need to be diluted for future mouse model experiments. Of the four primary anthocyanins in elderberry, cyanidin 3-sambubioside and cyanidin 3-glucoside were identified as the major tumor-inhibiting, immune-inducing components in different active fractions separated from elderberry. The positive benefits of active fractions on tumor suppression and potentially on modulation of immune-inducing mechanisms provide further support for the use of bioactive phytochemicals in preventative cancer treatment

Isolation and characterization of active elderberry fractions that inhibit melanoma growth in vitro and in vivo

The incidence rates of melanoma continue to rise annually despite recent progression in cancer treatments. Cancer is the most prevalent amongst elderly individuals, where immunosenescence has compromised some immune function, and therefore decreased certain tumor detection abilities. Current tumor removal strategies include radiation, chemotherapy and surgical excision: treatments that aim to lower cancer cells, but may also affect normal cells in the process. In the case of chemotherapy, which targets and kills rapidly dividing cells, many immune cells are lowered as a side effect, leaving many patients immune-suppressed and more susceptible to infection. There is a need for naturopathic treatments capable of decreasing tumor cell proliferation without compromising the body\u27s normal immune function. Extracts from elderberry (Sambucus nigra) may be able to satisfy this need. Previous reports suggest that phytochemicals, such as the ones present in elderberry, may stimulate the immune response by secretion of cytokines, provide antioxidant protection to prevent cellular damage, and inhibit tumor growth directly. Our primary goal was to separate the active components of elderberry and assess their inhibitory effects on the growth of multiple cancerous and transformed cell lines, as well as characterize their effects on stimulation of T lymphocyte proliferation and IL-2 secretion in vitro. Murine melanoma model experiments were also performed with crude elderberry and elderberry fractions to analyze the tumor-suppressive activity of elderberry treatments in vivo. Spleen cell proliferation and in vivo experiments were also performed with different aged groups of mice to uncover the tumor -inhibiting and immune-inducing effects of elderberry and active elderberry fractions on aged mice. Active elderberry fractions were then preliminarily identified. All separated elderberry fractions were able to significantly suppress the growth of B16-F10 murine melanoma and SH-SY5Y human neuroblastoma cells in vitro. Several separated fractions also inhibited growth of a human melanoma cell line, MeWo, and a transformed non-cancerous line, CHO-K1. When incubated with concanavalin A (Con A, a known mitogen) and spleen cells from a middle aged and old mouse, separated fractions of elderberry did not increase proliferation above the positive control (cells incubated with con A only) , however, they induced a larger proliferation response in the older mouse spleen cells. Three active fractions induced secretion of IL-2 from spleen cells above the positive control. In general, mice induced to produce tumors developed smaller, localized tumors when treated with crude elderberry compared to mice treated with water, whose tumors were larger and metastatic. The active elderberry fractions were too potent to be successfully implemented in an in vivo experiment, and need to be diluted for future mouse model experiments. Of the four primary anthocyanins in elderberry, cyanidin 3-sambubioside and cyanidin 3-glucoside were identified as the major tumor-inhibiting, immune-inducing components in different active fractions separated from elderberry. The positive benefits of active fractions on tumor suppression and potentially on modulation of immune-inducing mechanisms provide further support for the use of bioactive phytochemicals in preventative cancer treatment

Development of neoplasms in pediatric patients with rheumatic disease exposed to anti-tumor necrosis factor therapies: a single Centre retrospective study

Abstract Background Anti-TNF (Tumor necrosis factor) therapy is effective in treating pediatric patients with refractory rheumatic disease. There is however a concern that anti-TNF usage may increase the risk of malignancy. Reports on specific types of malignancy in this patient population have been emerging over the past decade, but there is a need for additional malignancy reports, as these events are rare. Therefore, a retrospective chart review was performed on the biologic database of pediatric rheumatology patients at The Hospital for Sick Children (SickKids) from 1997 to 2013 for neoplasms, patient demographic information and rheumatologic treatment course. Findings 6/357 (1.68%) rheumatology patients treated with anti-TNF therapy between 1997 and 2013 developed neoplasms. One patient had two malignancies. One patient had a benign neoplasm. Cases were exposed to etanercept, infliximab or both. Neoplasms developed late after anti-TNF exposure (median 5.0 years) and infliximab treatment was associated with a shorter time to malignancy. The neoplasms identified were as follows: 2 renal clear cell carcinoma, 1 pilomatricoma, 1 nasopharyngeal carcinoma, 1 Ewing’s sarcoma, 1 hepatic T-cell lymphoma, 1 lymphoproliferative disease. Conclusions The malignancy rate at our centre is low, however more than half of the neoplasms identified were rare and unusual in the pediatric population. The 5-year malignancy-free probability for patients with juvenile idiopathic arthritis (JIA) treated with biologic therapy was 97% from our database. Long-term screening for rare neoplasms is important as part of the safety monitoring for any pediatric rheumatology patient receiving anti-TNF therapy