Sterol-like drugs potentiate statin-triggered prostate cancer cell death by inhibiting SREBP2 nuclear translocation.

There is an urgent need to provide immediate and effective options for the treatment of prostate cancer (PCa) to prevent progression to lethal castration-resistant PCa (CRPC). The mevalonate (MVA) pathway is dysregulated in PCa, and statin drugs commonly prescribed for hypercholesterolemia, effectively target this pathway. Statins exhibit anti-PCa activity, however the resulting intracellular depletion of cholesterol triggers a feedback loop that restores MVA pathway activity, thus diminishing statin efficacy and contributing to resistance.

Anticolitic activity of prodigiosin loaded with selenium nanoparticles on acetic acid-induced colitis in rats.

Ulcerative colitis (UC) is a chronic autoimmune inflammatory disease associated with extensive mucosal damage. Prodigiosins (PGs) are natural bacterial pigments with well-known antioxidant and immunosuppressive properties. In the current study, we examined the possible protective effect of PGs loaded with selenium nanoparticles (PGs-SeNPs) against acetic acid (AcOH)-induced UC in rats.

Mevalonate Pathway Inhibition Slows Breast Cancer Metastasis via Reduced -glycosylation Abundance and Branching.

Aberrant -glycan Golgi remodeling and metabolism are associated with epithelial-mesenchymal transition (EMT) and metastasis in patients with breast cancer. Despite this association, the -glycosylation pathway has not been successfully targeted in cancer. Here, we show that inhibition of the mevalonate pathway with fluvastatin, a clinically approved drug, reduces both -glycosylation and -glycan-branching, essential components of the EMT program and tumor metastasis.

Statins as Anticancer Agents in the Era of Precision Medicine.

Statins are widely prescribed cholesterol-lowering drugs that inhibit HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate metabolic pathway. Multiple lines of evidence indicate that certain cancers depend on the mevalonate pathway for growth and survival, and, therefore, are vulnerable to statin therapy. However, these immediately available, well-tolerated, and inexpensive drugs have yet to be successfully repurposed and integrated into cancer patient care.

A pilot window-of-opportunity study of preoperative fluvastatin in localized prostate cancer.

Background: Statins inhibit HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway. Epidemiological and pre-clinical evidence support an association between statin use and delayed prostate cancer (PCa) progression. Here, we evaluated the effects of neoadjuvant fluvastatin treatment on markers of cell proliferation and apoptosis in men with localized PCa.

Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism.

Mitochondrial metabolism is an attractive target for cancer therapy. Reprogramming metabolic pathways could improve the ability of metabolic inhibitors to suppress cancers with limited treatment options, such as triple-negative breast cancer (TNBC). Here we show that BTB and CNC homology1 (BACH1), a haem-binding transcription factor that is increased in expression in tumours from patients with TNBC, targets mitochondrial metabolism.

Fibroblast-derived CXCL12 promotes breast cancer metastasis by facilitating tumor cell intravasation.

The chemokine CXCL12 has been shown to regulate breast tumor growth, however, its mechanism in initiating distant metastasis is not well understood. Here, we generated a novel conditional allele of Cxcl12 in mice and used a fibroblast-specific Cre transgene along with various mammary tumor models to evaluate CXCL12 function in the breast cancer metastasis. Ablation of CXCL12 in stromal fibroblasts of mice significantly delayed the time to tumor onset and inhibited distant metastasis in different mouse models.

STAT1 gene deficient mice develop accelerated breast cancer growth and metastasis which is reduced by IL-17 blockade.

Signal transducer and activator of transcription 1 (STAT1) mediates interferon gamma signaling which activates the expression of various genes related to apoptosis, inflammation, cell cycle and angiogenesis. Several experimental and clinical studies have investigated the role of STAT1 in primary tumor growth in breast cancer; however, its role in tumor metastasis remains to be determined. To determine the role of STAT1 in breast cancer metastasis, we analyzed growth and metastasis in WT or STAT1 mice orthotopically implanted with metastatic 4T1.

Profile of palbociclib in the treatment of metastatic breast cancer.

Breast cancer is the most common cancer diagnosed in women. Each year, thousands die either because of disease progression or failure of treatment. Breast cancer is classified into different subtypes based on the molecular expression of estrogen receptor (ER), progesterone receptor, and/or human epidermal growth factor receptor 2 (HER2).

TRPV2 is a novel biomarker and therapeutic target in triple negative breast cancer.

Transient receptor potential vanilloid type-2 (TRPV2) is an ion channel that is triggered by agonists like cannabidiol (CBD). Triple negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Chemotherapy is still the first line for the treatment of TNBC patients; however, TNBC usually gains rapid resistance and unresponsiveness to chemotherapeutic drugs.

Novel role of cannabinoid receptor 2 in inhibiting EGF/EGFR and IGF-I/IGF-IR pathways in breast cancer.

Breast cancer is the second leading cause of cancer deaths among women. Cannabinoid receptor 2 (CNR2 or CB2) is an integral part of the endocannabinoid system. Although CNR2 is highly expressed in the breast cancer tissues as well as breast cancer cell lines, its functional role in breast tumorigenesis is not well understood.

Cannabinoid receptor-2 agonist inhibits macrophage induced EMT in non-small cell lung cancer by downregulation of EGFR pathway.

JWH-015, a cannabinoid receptor 2 (CB2) agonist has tumor regressive property in various cancer types. However, the underlying mechanism by which it acts in lung cancer is still unknown. Tumor associated macrophage (TAM) intensity has positive correlation with tumor progression.

Conditioning solid tumor microenvironment through inflammatory chemokines and S100 family proteins.

Recently, there has been growing attention to the role of the tumor microenvironment (TME) in cancer growth, metastasis and emergence of chemotherapy resistance. Stromal and tumor cells make up the TME and interact with each other through a complex cross-talk manner. This interaction is facilitated by a variety of growth factors, cytokines, chemokines and S100 proteins.

Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: novel anti-tumor mechanisms of Cannabidiol in breast cancer.

The anti-tumor role and mechanisms of Cannabidiol (CBD), a non-psychotropic cannabinoid compound, are not well studied especially in triple-negative breast cancer (TNBC). In the present study, we analyzed CBD's anti-tumorigenic activity against highly aggressive breast cancer cell lines including TNBC subtype. We show here -for the first time-that CBD significantly inhibits epidermal growth factor (EGF)-induced proliferation and chemotaxis of breast cancer cells.

RAGE mediates S100A7-induced breast cancer growth and metastasis by modulating the tumor microenvironment.

RAGE is a multifunctional receptor implicated in diverse processes including inflammation and cancer. In this study, we report that RAGE expression is upregulated widely in aggressive triple-negative breast cancer (TNBC) cells, both in primary tumors and in lymph node metastases. In evaluating the functional contributions of RAGE in breast cancer, we found that RAGE-deficient mice displayed a reduced propensity for breast tumor growth.