☆ 4.7 Article

Sulforaphane, a natural constituent of broccoli, prevents cell death and inflammation in nephropathy

JOURNAL OF NUTRITIONAL BIOCHEMISTRY (2012)

Journal

JOURNAL OF NUTRITIONAL BIOCHEMISTRY

Volume 23, Issue 5, Pages 494-500

Publisher

ELSEVIER SCIENCE INC

DOI: 10.1016/j.jnutbio.2011.02.004

Keywords

Sulforaphane; Natural compound; Nephropathy; Inflammation; Cell death; Cisplatin

Funding

NIH/NIAAA
Consejo Nacional de Ciencia y Tecnologia (CONACYT) [129838]
Direccion General de Asuntos del Personal Academic (DGAPA) [201910]
Hungarian Research Scientific Fund (OTKA) fellowship [MB08-A 80238]

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Abstract

Cisplatin (cis-diamminedichloroplatinum II, CIS) is a potent and widely used chemotherapeutic agent to treat various malignancies, but its therapeutic use is limited because of dose-dependent nephrotoxicity. Cell death and inflammation play a key role in the development and progression of CIS-induced nephropathy. Sulforaphane (SFN), a natural constituent of cruciferous vegetables such as broccoli, Brussels sprouts, etc., has been shown to exert various protective effects in models of tissue injury and cancer. In this study, we have investigated the role of prosurvival, cell death and inflammatory signaling pathways using a rodent model of CIS-induced nephropathy, and explored the effects of SFN on these processes. Cisplatin triggered marked activation of stress signaling pathways [p53, Jun N-terminal kinase (JNK), and p38-alpha mitogen-activated protein kinase (MAPK)] and promoted cell death in the kidneys (increased DNA fragmentation, caspases-3/7 activity, terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick-end labeling), associated with attenuation of various prosurvival signaling pathways [e.g., extracellular signal-regulated kinase (ERK) and p38-beta MAPK]. Cisplatin also markedly enhanced inflammation in the kidneys [promoted NF-kappa B activation, increased expression of adhesion molecules ICAM and VCAM, enhanced tumor necrosis factor-alpha (TNF-alpha) levels and inflammatory cell infiltration]. These effects were significantly attenuated by pretreatment of rodents with SFN. Thus, the cisplatin-induced nephropathy is associated with activation of various cell death and proinflammatory pathways (p53. JNK, p38-alpha, TNF-alpha and NF-kappa B) and impairments of key prosurvival signaling mechanisms (ERK and p38-beta). SFN is able to prevent the CIS-induced renal injury by modulating these pathways, providing a novel approach for preventing this devastating complication of chemotherapy. Published by Elsevier Inc.

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Sulforaphane: An emergent anti-cancer stem cell agent

Leandro de Lima Coutinho, Tharcisio Citrangulo Tortelli Junior, Maria Cristina Rangel

Summary: Cancer is a global public health problem with high morbidity and mortality rates. Plant-derived compounds, particularly sulforaphane (SFN), have shown chemopreventive and anticancer effects. SFN has also demonstrated the ability to target cancer stem cells (CSCs), a specific population of cancer cells with stem-like properties. This is particularly significant as most conventional chemotherapeutic agents cannot effectively target CSCs, which often exist in a quiescent state. SFN has the potential to be used in combination with conventional antineoplastic drugs in clinical settings.

FRONTIERS IN ONCOLOGY (2023)