NO to Breast: When, Why and Why Not?

Pervin, Shehla; Chaudhuri, Gautam; Singh, Rajan

doi:10.2174/138161210790232130

Cited by 19 publications

(15 citation statements)

References 162 publications

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“…In breast cancer models, increased oxidative stress can induce initiation of a tumor as well as promote tumor growth [44]. Therefore, agents that can reduce excess oxidative stress offer potential as anti-cancer agents for the breast.…”

Section: Anti-oxidant Activitymentioning

confidence: 99%

d-Limonene: a bioactive food component from citrus and evidence for a potential role in breast cancer prevention and treatment

et al. 2010

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Although limited, observations from cell culture, animal, and epidemiological studies support the presence of anti-cancer properties in citrus peel and the primary bioactive food constituent, d-limonene. Early evidence from animal models suggests that when ingested, d-limonene exhibits a wide spectrum of biologic activity including chemotherapeutic and chemopreventive effects. In some of these early models, an analog of d-limonene, perillyl alcohol, demonstrated a more potent effect than d-limonene itself. Yet, when perillyl alcohol advanced to clinical trials, several trials were ended early due to doselimiting toxicities. Alternatively, oral d-limonene administration in humans is well tolerated even at high doses supporting its investigation as a potential bioactive for cancer prevention. Though the exact mechanisms of action of d-limonene are unclear, immune modulation and antiproliferative effects are commonly reported. Here, we review the pre-clinical evidence for d-limonene's anticancer mechanisms, bioavailability, and safety, as well as the evidence for anti-cancer effects in humans, focusing on studies relevant to its use in the prevention and treatment of breast cancer.

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Section: Anti-oxidant Activitymentioning

confidence: 99%

d-Limonene: a bioactive food component from citrus and evidence for a potential role in breast cancer prevention and treatment

et al. 2010

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“…13 Oxidative stress, particularly stress associated with nitric oxide production (NO), has been linked to the development and progression of cancer at different sites including breast cancer. 14,15 Isoprostane formation is directly associated with oxidative stress caused by NO synthesis in vivo . 16,17 Among the many markers of oxidative stress, 18 F 2 isoprostanes are a relatively good measure because they are stable and specific and are formed directly by chemical oxidation.…”

Section: Introductionmentioning

confidence: 99%

Soy foods and urinary isoprostanes: Results from a randomized study in premenopausal women

et al. 2012

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In addition to their antiestrogenic effects, soy isoflavones may protect against cancer through alternate biologic actions including antioxidant properties. This randomized, crossover study explored the relation between dietary isoflavone intake through common soy foods and oxidative stress quantified by urinary isoprostane levels. Eighty-two women aged 39.2±6.1 years were randomized to a high soy diet of 2 soy food servings per day and a low soy diet of <3 servings per week for 6 months each, separated by a 1 month washout period. Urine samples were collected at baseline and at the end of each dietary period. Urinary isoprostane levels were measured using enzyme-linked immunosorbent assays (ELISA) and adjusted for creatinine levels. Mixed models using log-transformed values were applied to evaluate the effect of the high soy diet. Unadjusted isoprostane excretion levels were lower during the high than the low soy diet, but this effect was not statistically significant (p=0.81). After adjustment for urinary creatinine, isoprostane excretion was slightly higher during the high soy diet (p=0.02), an observation that was confirmed in a regression analysis between urinary isoflavones and isoprostanes during the high soy diet. The original association remained significant when restricted to adherent participants; however, this effect disappeared after exclusion of three extreme values. In agreement with several previous reports, these findings do not support the hypothesis that soy exerts antioxidant effects as measured by urinary isoprostane excretions, but additional markers of oxidative stress need to be investigated in future studies.

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“…The latter cytotoxic effects have been associated with activation of cells involved in inflammatory responses and induction of inducible NOS (iNOS) (7). Several studies suggest that high NO concentrations generated by exogenous sources or forced overexpression of iNOS may be used to kill tumor cells; paradoxically, iNOS is overexpressed in many tumors, and overexpression of iNOS often correlates with poor prognosis, leading to iNOS inhibition as a proposed target for cancer therapy (8,9). cGMP-independent posttranslational nitrosation of caspase and pol(ADP-ribose) polymerase are reported as antiapoptotic cell defenses (10,11).…”

mentioning

confidence: 99%

Estrogen-Induced Apoptosis of Breast Epithelial Cells Is Blocked by NO/cGMP and Mediated by Extranuclear Estrogen Receptors

et al. 2010

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Estrogen action, via both nuclear and extranuclear estrogen receptors (ERs), induces a variety of cellular signals that are prosurvival or proliferative, whereas nitric oxide (NO) can inhibit apoptosis via caspase S-nitrosylation and via activation of soluble guanylyl cyclase to produce cGMP. The action of 17β-estradiol (E(2)) at ER is known to elicit NO signaling via activation of NO synthase (NOS) in many tissues. The MCF-10A nontumorigenic, mammary epithelial cell line is genetically stable and insensitive to estrogenic proliferation. In this cell line, estrogens or NOS inhibitors alone had no significant effect, whereas in combination, apoptosis was induced rapidly in the absence of serum; the presence of inducible NOS was confirmed by proteomic analysis. The application of pharmacological agents determined that apoptosis was dependent upon NO/cGMP signaling via cyclic GMP (cGMP)-dependent protein kinase and could be replicated by inhibition of the phosphatidylinositol 3 kinase/serine-threonine kinase pathway prior to addition of E(2). Apoptosis was confirmed by nuclear staining and increased caspase-3 activity in E(2) + NOS inhibitor-treated cells. Apoptosis was partially inhibited by a pure ER antagonist and replicated by agonists selective for extranuclear ER. Cells were rescued from E(2)-induced apoptosis after NOS blockade, by NO-donors and cGMP pathway agonists; preincubation with NO donors was required. The NOS and ER status of breast cancer tissues is significant in etiology, prognosis, and therapy. In this study, apoptosis of preneoplastic mammary epithelial cells was triggered by estrogens via a rapid, extranuclear ER-mediated response, after removal of an antiapoptotic NO/cGMP/cGMP-dependent protein kinase signal.

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NO to Breast: When, Why and Why Not?

Cited by 19 publications

References 162 publications

d-Limonene: a bioactive food component from citrus and evidence for a potential role in breast cancer prevention and treatment

d-Limonene: a bioactive food component from citrus and evidence for a potential role in breast cancer prevention and treatment

Soy foods and urinary isoprostanes: Results from a randomized study in premenopausal women

Estrogen-Induced Apoptosis of Breast Epithelial Cells Is Blocked by NO/cGMP and Mediated by Extranuclear Estrogen Receptors

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