β-Sitosterol, β-Sitosterol Glucoside, and a Mixture of β-Sitosterol and β-Sitosterol Glucoside Modulate the Growth of Estrogen-Responsive Breast Cancer Cells In Vitro and in Ovariectomized Athymic Mice
TL;DR: Although B SSG comprises only 1% of MC, BSSG made MC less estrogenic than BSS alone in vitro, however, dietary BSS and MC protected against E(2)-stimulated MCF-7 tumor growth and lowered circulating E( 2) levels.
Abstract: We hypothesized that the phytosterols beta-sitosterol (BSS), beta-sitosterol glucoside (BSSG), and Moducare (MC; BSS:BSSG = 99:1) could modulate the growth of estrogen-dependent human breast cancer cells in vitro and in vivo. The present study evaluated the estrogenic and antiestrogenic effects of BSS, BSSG, and MC (0.001 to 150 micromol/L) on the proliferation of Michigan Cancer Foundation 7 (MCF-7) cells in vitro. Both BSS (>1 micromol/L) and MC (>50 micromol/L) increased MCF-7 cell proliferation. Treatment with 150 micro mol/L of BSS and MC increased cell growth by 2.4 and 1.5 times, respectively, compared to the negative control (NC) group. However, BSSG had no effect at the concentrations tested. The effects of dietary BSS, BSSG, and MC on the growth of MCF-7 cells implanted in ovariectomized athymic mice were also evaluated. Estrogenic effects of the phytosterols were evaluated in the NC, BSS, BSSG, and MC treatment groups, and antiestrogenic effects were evaluated in the 17 beta-estradiol (E(2)), E(2) + BSS, E(2) + BSSG, and E(2) + MC treatment groups. Mice were treated with dietary BSS (9.8 g/kg AIN93G diet), BSSG (0.2 g/kg diet), or MC (10.0 g/kg diet) for 11 wk. Dietary BSS, BSSG, and MC did not stimulate MCF-7 tumor growth. However, dietary BSS, BSSG, and MC reduced E(2)-induced MCF-7 tumor growth by 38.9% (P < 0.05), 31.6% (P = 0.08), and 42.13% (P < 0.05), respectively. The dietary phytosterols lowered serum E(2) levels by 35.1, 30.2, and 36.5% in the E(2) + BSS, E(2) + BSSG, and E(2) + MC groups, respectively (P < 0.05), compared to that of the E(2) treatment group. Estrogen-responsive pS2 mRNA expression in tumors did not differ among groups, but expression of the antiapoptotic marker B-cell lymphoma/leukemia-2 (bcl-2) in tumors from the E(2) + MC group was downregulated, compared to that of the E(2) treatment group. In summary, BSS and MC stimulated MCF-7 cell growth in vitro. Although BSSG comprises only 1% of MC, BSSG made MC less estrogenic than BSS alone in vitro. However, dietary BSS and MC protected against E(2)-stimulated MCF-7 tumor growth and lowered circulating E(2) levels.
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TL;DR: A simple and efficient green chemistry approach is designed for the synthesis of colloidal silver nanoparticles (b-AgNPs) that is formed by the reduction of silver nitrate (AgNO3) solution using Olax scandens leaf extract to demonstrate the multifunctional biological activities of bio-synthesized AgNPs.
Abstract: In this report, we have designed a simple and efficient green chemistry approach for the synthesis of colloidal silver nanoparticles (b-AgNPs) that is formed by the reduction of silver nitrate (AgNO3) solution using Olax scandens leaf extract. The colloidal b-AgNPs, characterized by various physico-chemical techniques exhibit multifunctional biological activities (4-in-1 system). Firstly, bio-synthesized silver nanoparticles (b-AgNPs) shows enhanced antibacterial activity compared to chemically synthesize silver nanoparticles (c-AgNPs). Secondly, b-AgNPs show anti-cancer activities to different cancer cells (A549: human lung cancer cell lines, B16: mouse melanoma cell line & MCF7: human breast cancer cells) (anti-cancer). Thirdly, these nanoparticles are biocompatible to rat cardiomyoblast normal cell line (H9C2), human umbilical vein endothelial cells (HUVEC) and Chinese hamster ovary cells (CHO) which indicates the future application of b-AgNPs as drug delivery vehicle. Finally, the bio-synthesized AgNPs show bright red fluorescence inside the cells that could be utilized to detect the localization of drug molecules inside the cancer cells (a diagnostic approach). All results together demonstrate the multifunctional biological activities of bio-synthesized AgNPs (4-in-1 system) that could be applied as (i) anti-bacterial & (ii) anti-cancer agent, (iii) drug delivery vehicle, and (iv) imaging facilitator. To the best of our knowledge, there is not a single report of biosynthesized AgNPs that demonstrates the versatile applications (4-in-1 system) towards various biomedical applications. Additionally, a plausible mechanistic approach has been explored for the synthesis of b-AgNPs and its anti-bacterial as well as anti-cancer activity. We strongly believe that bio-synthesized AgNPs will open a new direction towards various biomedical applications in near future.
408 citations
TL;DR: Mounting evidence supports a role for phytosterols in protecting against cancer development and could be incorporated in diet not only to lower the cardiovascular disease risk, but also to potentially prevent cancer development.
Abstract: Phytosterol and stanol (or phytosterols) consumption reduces intestinal cholesterol absorption, leading to decreased blood LDL-cholesterol levels and lowered cardiovascular disease risk. However, other biological roles for plant sterols and stanols have also been proposed. The objective of this review is to critically examine results from recent research regarding the potential effects and mechanisms of action of phytosterols on forms of cancer. Considerable emerging evidence supports the inhibitory actions of phytosterols on lung, stomach, as well as ovarian and breast cancer. Phytosterols seem to act through multiple mechanisms of action, including inhibition of carcinogen production, cancer-cell growth, angiogenesis, invasion and metastasis, and through the promotion of apoptosis of cancerous cells. Phytosterol consumption may also increase the activity of antioxidant enzymes and thereby reduce oxidative stress. In addition to altering cell-membrane structure and function, phytosterols probably promote apoptosis by lowering blood cholesterol levels. Moreover, consumption of phytosterols by healthy humans at the recommended level of 2 g per day does not cause any major health risks. In summary, mounting evidence supports a role for phytosterols in protecting against cancer development. Hence, phytosterols could be incorporated in diet not only to lower the cardiovascular disease risk, but also to potentially prevent cancer development.
351 citations
Cites background from "β-Sitosterol, β-Sitosterol Glucosid..."
...Ju et al. (2004) examined the action of phytosterols (9.8 g per kg diet) on growth of estrogen-dependent human breast cancer cells in ovarectomised mice implanted with or without 17bestradiol. b-Sitosterol consumption did not affect the growth of the breast cancer cells in 17b-estradiol-untreated…...
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...…actions, mounting evidence suggests that phytosterols possess anti-cancer effects (Choi et al., 2007) against cancer of the lung (Mendilaharsu et al., 1998), stomach (De Stefani et al., 2000), ovary (McCann et al., 2003) and estrogen-dependent human breast cancer (Ju et al., 2004)....
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TL;DR: The primary research recommendation is that the impact of isoflavones on breast tissue needs to be evaluated at the cellular level in women at high risk for breast cancer.
Abstract: The impact of soyfood intake on breast cancer risk has been investigated extensively. Much of this focus can be attributed to the soybean being a dietary source that is uniquely rich in isoflavones. The chemical structure of isoflavones is similar to that of estrogen, and isoflavones bind to both estrogen receptors (ER alpha and ER beta) (although they preferentially bind to and activate ER beta) and exert estrogen-like effects under some experimental conditions. Isoflavones also possess nonhormonal properties that are associated with the inhibition of cancer cell growth. Thus, there are several possible mechanisms by which soy may reduce the risk of breast cancer. However, the role of isoflavones in breast cancer has become controversial because, in contrast to the possible beneficial effects, some data from in vitro and animal studies suggest that isoflavones, especially genistein, the aglycone of the main soybean isoflavone genistin, may stimulate the growth of estrogen-sensitive tumors. Limited human data directly address the tumor-promoting effects of isoflavones and soy. Because the use of soyfoods and isoflavone supplements is increasing, it is important from a public health perspective to understand the impact of these products on breast cancer risk in women at high risk of the disease and on the survival of breast cancer patients. To this end, a workshop was held in November 2005 to review the existing literature and to make research recommendations. This paper summarizes the workshop findings and recommendations. The primary research recommendation is that the impact of isoflavones on breast tissue needs to be evaluated at the cellular level in women at high risk for breast cancer.
306 citations
TL;DR: The current state of knowledge regarding the anticancer effects of phytosterols is summarized, including the boosting of immune recognition of cancer, influencing hormonal dependent growth of endocrine tumors, and altering sterol biosynthesis.
Abstract: Phytochemicals have been proposed to offer protection against a variety of chronic ailments including cardiovascular diseases, obesity, diabetes, and cancer As for cancer protection, it has been estimated that diets rich in phytochemicals can significantly reduce cancer risk by as much as 20% Phytosterols are specific phytochemicals that resemble cholesterol in structure but are found exclusively in plants Phytosterols are absorbed from the diet in small but significant amounts Epidemiological data suggest that the phytosterol content of the diet is associated with a reduction in common cancers including cancers of the colon, breast, and prostate The means by which dietary phytosterols may be achieving these effects is becoming clearer from molecular studies with tumorigenic research models Phytosterols affect host systems potentially enabling more robust antitumor responses, including the boosting of immune recognition of cancer, influencing hormonal dependent growth of endocrine tumors, and altering sterol biosynthesis In addition, phytosterols have effects that directly inhibit tumor growth, including the slowing of cell cycle progression, the induction of apoptosis, and the inhibition of tumor metastasis This review summarizes the current state of knowledge regarding the anticancer effects of phytosterols
293 citations
TL;DR: Phytosterols are a subgroup of the steroids, as an important class of bioorganic molecules, widespread in plants, animals, marines as well as fungi and have similarity to cholesterol in structure.
Abstract: Aims : Phytosterols are a subgroup of the steroids, as an important class of bioorganic molecules,widespread in plants, animals, marines as well as fungi and have similarity to cholesterol in structure. These compounds have a long history of consumption as food or pharmaceutical products, and generally recognized as safe without undesirable side effects.
244 citations
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TL;DR: Many bioactive compounds are extranutritional constituents that typically occur in small quantities in foods and are grouped accordingly as phenolic compounds, including their subcategory, flavonoids as discussed by the authors.
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TL;DR: The AIN-93 rodent diets were formulated to substitute for the previous version (AIN-76A) and to improve the performance of animals that consume them and are better choices for studies with laboratory rodents.
Abstract: The AIN-93 rodent diets were formulated to substitute for the previous version (AIN-76A) and to improve the performance of animals that consume them. They are called AIN-93G, formulated for growth, and AIN-93M, for maintenance. Major changes included substituting cornstarch for sucrose and soybean oil for corn oil and increasing the amount in order to supply both essential fatty acids (linoleic and linolenic). L-Cystine was substituted for DL-methionine to supplement the casein component. The mineral mix was reformulated to lower the amounts of phosphorus, manganese and chromium, to increase the amount of selenium, and to add molybdenum, silicon, fluoride, nickel, boron, lithium and vanadium. The amounts of vitamins E, K-1 and B-12 were increased over those in the AIN-76A vitamin mix. The AIN-93G diet contains 200 g of casein and 70 g of soybean oil/kg diet. The maintenance diet (AIN-93M) contains 140 g of casein and 40 g of soybean oil/kg diet. The 1993 diets have a better balance of essential nutrients than the 1976 diet and are better choices for studies with laboratory rodents.
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TL;DR: Phytosterols and phytostanols have received much attention in the last five years because of their cholesterol-lowering properties and the popularity of these products has caused the medical and biochemical community to focus much attention on phytosterol research activity.
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