Oxidative Stress in the <i>in vivo </i><scp>DMBA</scp> Rat Model of Breast Cancer: Suppression by a Voltage‐gated Sodium Channel Inhibitor (<scp>RS</scp>100642)

Batçıoğlu, Kadir; Uyumlu, Ayşe Burçin; Satılmış, Basri; Yildirim, Battal; Yücel, Neslihan; Demirtaş, Hakan; Onkal, Rustem; Guzel, R. Mine; Djamgoz, Mustafa B.A.

doi:10.1111/j.1742-7843.2012.00880.x

Cited by 48 publications

(38 citation statements)

References 47 publications

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“…Therefore, targeting oxidative stress proposes potential new therapeutic approaches . Consistent with previous studies , we observed an overt oxidative stress status in mice of D1 group demonstrated as increased MDA and TOS in tumor tissue. Administration of simvastatin especially at its higher dose as well as tamoxifen decreased the severity of oxidative stress.…”

Section: Discussionsupporting

confidence: 91%

Therapeutic effect of simvastatin on DMBA‐induced breast cancer in mice

Karimi

Ashrafi

Shomali

et al. 2018

Fundamemntal Clinical Pharma

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Preclinical studies have shown positive effects of statins against specific cancers. This study aimed to determine the therapeutic effect of simvastatin in 12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer. Female albino mice were divided into two groups, with or without DMBA administration. After tumor appearance, DMBA-treated group was further divided into four groups (D1-D4) as control (D1), treated with simvastatin at 80 and 40 mg/kg/day, orally (D2 and D3) and tamoxifen (50 mg/kg/day, orally) treated group (D4). After 4 weeks, animals were sacrificed, serum samples were collected and tumors were dissected for histopathological study and determination of selected parameters. The tumor marker carcinoma antigen 15-3 (CA15-3), oxidative stress parameters and prostaglandin E2 (PGE2) levels were analyzed in serum and tumors in experimental groups. Tamoxifen and high dose of simvastatin improved parameters of mammary carcinogenesis including mean tumor volume, body weight and percent of mortality as compared to mice with breast tumors without treatment (D1). Additionally, simvastatin usage increased total antioxidant capacity (TAC) level, paraoxonase 1 (PON1) activity in serum and decreased total oxidant status (TOS) and malondialdehyde (MDA) levels in tumors similar to tamoxifen. No significant decrease was found in serum CA 15-3 and tumor PGE2 levels in simvastatin and tamoxifen treated groups as compared to D1 group. These data suggest that simvastatin has anticancer effects which are relatively similar to that of tamoxifen in an animal model of breast cancer.

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Section: Discussionsupporting

confidence: 91%

Therapeutic effect of simvastatin on DMBA‐induced breast cancer in mice

Karimi

Ashrafi

Shomali

et al. 2018

Fundamemntal Clinical Pharma

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“…Batcioglu et al 61 showed the importance of VGSCs inhibition in a rat model of induced breast cancer in order to inhibit antioxidant response. They observed a survival improvement in rats treated with a VGSC blocker.…”

Section: Voltage-gated Sodium Channelsmentioning

confidence: 99%

Cancer: fundamentals behind pH targeting and the double-edged approach

Koltai¹

2016

OTT

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The highly regulated pH of cells and the less-regulated pH of the surrounding extracellular matrix (ECM) is the result of a delicate balance between metabolic processes and proton production, proton transportation, chemical buffering, and vascular removal of waste products. Malignant cells show a pronounced increase in metabolic processes where the 10- to 15-fold rise in glucose consumption is only the tip of the iceberg. Aerobic glycolysis (Warburg effect) is one of the hallmarks of cancer metabolism that implies excessive production of protons, which if stayed inside the cells would result in fatal intracellular acidosis (maintaining a strict acid–base balance is essential for the survival of eukaryotic cells). Malignant cells solve this problem by increasing mechanisms of proton transportation which expel the excess acidity. This allows cancer cells to keep a normal intracellular pH, or even overshooting this mechanism permits a slightly alkaline intracellular tendency. The proton excess expelled from malignant cells accumulates in the ECM, where chronic hypoxia and relative lack of enough blood vessels impede adequate proton clearance, thus creating an acidic microenvironment. This microenvironment is quite heterogeneous due to the tumor’s metabolic heterogeneity and variable degrees of hypoxia inside the tumor mass. The acidic environment (plus other necessary cellular modifications) stimulates migration and invasion and finally intravasation of malignant cells which eventually may result in metastasis. Targeting tumor pH may go in two directions: 1) increasing extracellular pH which should result in less migration, invasion, and metastasis; and 2) decreasing intracellular pH which may result in acidic stress and apoptosis. Both objectives seem achievable at the present state of the art with repurposed drugs. This hypothesis analyzes the altered pH of tumors and its implications for progression and metastasis and also possible repurposed drug combinations targeting this vulnerable side of cancer development. It also analyzes the double-edged approach, which consists in pharmacologically increasing intracellular proton production and simultaneously decreasing proton extrusion creating intracellular acidity, acid stress, and eventual apoptosis.

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“…There are three major ER-positive cell lines commonly used, such as MCF-7 [66], T47D [67], and ZR-75-1[68]. In addition, overexpression of genes involved in breast cancer and mutagenesis induced by the mouse mammary tumor virus (MMTV) or polyoma middle-T antigen (PyMT) [69], or treatment with chemical agents, such as 7,12-dimethylbenz(a)anthracene (DMBA) [70], medroxyprogesterone acetate (MPA) [71], or N-methyl-N-nitrosourea (NMU) [72], can induce ER-positive mammary tumors in experimental animals. Furthermore, estrogen-mediated mammary carcinogenesis models are based on long-term subcutaneous administration of estrogen using slow-release pellets or silastic tubes [73].…”

Section: Natural Products Against Er-positive Breast Cancermentioning

confidence: 99%

Role of dietary bioactive natural products in estrogen receptor-positive breast cancer

Bak

Gupta

Wahler

et al. 2016

Seminars in Cancer Biology

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Estrogen receptor (ER)-positive breast cancer, including luminal-A and -B, is the most common type of breast cancer. Extended exposure to estrogen is associated with an increased risk of breast cancer. Both ER-dependent and ER-independent mechanisms have been implicated in estrogen-mediated carcinogenesis. The ER-dependent pathway involves cell growth and proliferation triggered by the binding of estrogen to the ER. The ER-independent mechanisms depend on the metabolism of estrogen to generate genotoxic metabolites, free radicals and reactive oxygen species to induce breast cancer. A better understanding of the mechanisms that drive ER-positive breast cancer will help optimize targeted approaches to prevent or treat breast cancer. A growing emphasis is being placed on alternative medicine and dietary approaches toward the prevention and treatment of breast cancer. Many natural products and bioactive compounds found in foods have been shown to inhibit breast carcinogenesis via inhibition of estrogen induced oxidative stress as well as ER signaling. This review summarizes the role of bioactive natural products that are involved in the prevention and treatment of estrogen-related and ER-positive breast cancer.

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Oxidative Stress in the in vivo DMBA Rat Model of Breast Cancer: Suppression by a Voltage‐gated Sodium Channel Inhibitor (RS100642)

Cited by 48 publications

References 47 publications

Therapeutic effect of simvastatin on DMBA‐induced breast cancer in mice

Therapeutic effect of simvastatin on DMBA‐induced breast cancer in mice

Cancer: fundamentals behind pH targeting and the double-edged approach

Role of dietary bioactive natural products in estrogen receptor-positive breast cancer

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