PEITC treatment suppresses myeloid derived tumor suppressor cells to inhibit breast tumor growth

Gupta, Parul; Wright, Stephen E.; Srivastava, Sanjay

doi:10.4161/2162402x.2014.981449

Cited by 19 publications

(16 citation statements)

References 37 publications

(59 reference statements)

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“…RBC lysis step was repeated in case complete lysis not achieved. After lysis of RBCs, cells were washed with PBS followed by a second washing with FACS buffer (2% heat inactivated fetal bovine serum and 2 mM ethylenediaminetetraacetic acid (EDTA) in PBS) as described before by us [ 40 ]. PBMC from each mouse were equally divided into two groups.…”

Section: Methodsmentioning

confidence: 99%

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Immune consequences of penfluridol treatment associated with inhibition of glioblastoma tumor growth

2017

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Glioblastoma is the most common and lethal brain tumor associated with only 12% median survival rate of patients. Despite the development of advanced surgical, radiation or use of combinations of anti-cancer drugs, treatment for glioblastoma patients is still a challenge. The major contributing factor in glioblastoma progression and resistive nature is its ability to evade the immune surveillance. Hence, modulating the immune system in glioblastoma tumors could be an important strategy for anticancer therapeutics. Penfluridol, an antipsychotic drug has been shown to have anti-cancer properties in our recently published studies. The present study evaluates the immune response of penfluridol in glioblastoma tumors. Our results demonstrated that penfluridol treatment significantly suppressed glioblastoma tumor growth. Our current results demonstrated about 72% suppression of myeloid derived suppressor cells (MDSCs) with penfluridol treatment in mouse bearing U87MG glioblastoma tumors. MDSCs are known to increase regulatory T cells (Treg), which are immunosuppressive in nature and suppresses M1 macrophages that are tumor suppressive in nature. Our results also showed suppression of regulatory T cells as well as elevation of M1 macrophages with penfluridol treatment by 58% and 57% respectively. Decrease in CCL4 as well as IFNγ with penfluridol treatment was also observed indicating decrease in overall tumor inflammation. This is the first report demonstrating immune modulations by penfluridol treatment associated with glioblastoma tumor growth suppression prompting further investigation to establish penfluridol as a treatment option for glioblastoma patients.

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Section: Methodsmentioning

confidence: 99%

“…Diluted samples were divided into two tubes with 25ml each, after which, 15ml PBS was further added. Samples were gently layered over 10-15ml Ficoll-Paque reagent (GE Lifesciences) as described by us before [ 40 ]. Samples were gently centrifuged for 40minutes at 400 x g maintaining 20°C temperature and without applying any brakes.…”

Section: Methodsmentioning

confidence: 99%

Immune consequences of penfluridol treatment associated with inhibition of glioblastoma tumor growth

2017

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“…Our lab has shown the immune modulation by PEITC in mice bearing breast tumor xenografts. We observed that PEITC treatment significantly suppressed breast tumor growth by reducing myeloid derived tumor suppressor cells (MDSCs) and T regulatory lymphocytes [99].…”

Section: Phenethyl Isothiocyanatementioning

confidence: 99%

Role of Phytochemicals in Cancer Prevention

Ranjan

Ramachandran

Gupta

et al. 2019

IJMS

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The use of synthetic, natural, or biological agents to minimize the occurrence of cancer in healthy individuals is defined as cancer chemoprevention. Chemopreventive agents inhibit the development of cancer either by impeding DNA damage, which leads to malignancy or by reversing or blocking the division of premalignant cells with DNA damage. The benefit of this approach has been demonstrated in clinical trials of breast, prostate, and colon cancer. The continuous increase in cancer cases, failure of conventional chemotherapies to control cancer, and excessive toxicity of chemotherapies clearly demand an alternative approach. The first trial to show benefit of chemoprevention was undertaken in breast cancer patients with the use of tamoxifen, which demonstrated a significant decrease in invasive breast cancer. The success of using chemopreventive agents for protecting the high risk populations from cancer indicates that the strategy is rational and promising. Dietary components such as capsaicin, cucurbitacin B, isoflavones, catechins, lycopenes, benzyl isothiocyanate, phenethyl isothiocyanate, and piperlongumine have demonstrated inhibitory effects on cancer cells indicating that they may serve as chemopreventive agents. In this review, we have addressed the mechanism of chemopreventive and anticancer effects of several natural agents.

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“…FoxQ1 is highly expressed in triple‐negative BC, displays an inverse correlation with the levels of DACH1 and localizes to DACH1 promoter in BC cells . The DATS treatment led to decrease of FoxQ1 protein levels along with inhibiting BC progression and causing a decline in BC stem cell population . The phenethyl isothiocyanate (PEITC) from cruciferous vegetables is another compound that has shown promising anticancer activity via downregulation of HER2, pSTAT3 and Bcl‐xL, and upregulation of Bim, Bax and caspase‐3 in BC cells .…”

Section: Determinants Of Bc Risk: Considerations For Bc Prevention Anmentioning

confidence: 99%

“…The DATS treatment led to decrease of FoxQ1 protein levels along with inhibiting BC progression and causing a decline in BC stem cell population . The phenethyl isothiocyanate (PEITC) from cruciferous vegetables is another compound that has shown promising anticancer activity via downregulation of HER2, pSTAT3 and Bcl‐xL, and upregulation of Bim, Bax and caspase‐3 in BC cells . Withaferin‐A, an active compound from Withania Somnifera, induces mitotic arrest in tumors of MMTV‐ neu mice, decreases number and weight of tumors in N‐methyl‐N‐nitrosourea (NMU) induced rat BC model, decreases circulating leptin levels in rat plasma and downregulates transcription factor FoxQ1 and angiogenesis marker CD31 in treated tumors …”

Section: Determinants Of Bc Risk: Considerations For Bc Prevention Anmentioning

confidence: 99%

Translational opportunities for broad‐spectrum natural phytochemicals and targeted agent combinations in breast cancer

Nagaprashantha

Adhikari

Singhal

et al. 2017

Intl Journal of Cancer

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Breast cancer (BC) prevention and therapy in the context of life-style risk factors and biological drivers is a major focus of developmental therapeutics in oncology. Obesity, alcohol, chronic estrogen signaling and smoking have distinct BC precipitating and facilitating effects that may act alone or in combination. A spectrum of signaling events including enhanced oxidative stress and changes in estrogen-receptor (ER)-dependent and -independent signaling drive the progression of BC. Breast tumors modulate ERα/ERβ ratio, upregulate proliferative pathways driven by ERα and HER2 with a parallel loss and/or downregulation of tumor suppressors such as TP53 and PTEN which together impact the efficacy of therapeutic strategies and frequently lead to emergence of drug resistance. Natural phytochemicals modulate oxidative stress, leptin, integrin, HER2, MAPK, ERK, Wnt/β-catenin and NFκB signaling along with regulating ERα and ERβ, thereby presenting unique opportunities for both primary and combinatorial interventions in BC. In this regard, this article focuses on critical analyses of the evidence from multiple studies on the efficacy of natural phytochemicals in BC. In addition, areas in which the combinations of such effective natural phytochemicals with approved and/or developing anticancer agents can be translationally beneficial are discussed to derive evidence-based inference for addressing challenges in BC control and therapy.

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PEITC treatment suppresses myeloid derived tumor suppressor cells to inhibit breast tumor growth

Cited by 19 publications

References 37 publications

Immune consequences of penfluridol treatment associated with inhibition of glioblastoma tumor growth

Immune consequences of penfluridol treatment associated with inhibition of glioblastoma tumor growth

Role of Phytochemicals in Cancer Prevention

Translational opportunities for broad‐spectrum natural phytochemicals and targeted agent combinations in breast cancer

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