Cyanidin reverses cisplatin-induced apoptosis in HK-2 proximal tubular cells through inhibition of ROS-mediated DNA damage and modulation of the ERK and AKT pathways

Gao, Si; Chen, Tianfeng; Choi, Mei-Yuk; Liang, Yuanwei; Xue, Junyi; Wong, Yum-Shing

doi:10.1016/j.canlet.2012.12.029

Cited by 68 publications

(34 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, several pharmacological agents demonstrated anti-apoptotic effects by inhibiting Bax activation and accumulation in mitochondria. 24,25,29 In addition, our present work has further demonstrated compelling evidence for tubular apoptosis via inhibition of formation of ROS and secretion of TNF-α, which are known to activate the extrinsic pathway of apoptosis through death receptors. Alternatively, death receptors can generate ROS and enhance cisplatininduced acute kidney injury.…”

Section: Discussionsupporting

confidence: 59%

Molecular mechanisms underlying attenuation of cisplatin-induced acute kidney injury by epicatechin gallate

Malik

Suchal

Bhatia

et al. 2016

Laboratory Investigation

View full text Add to dashboard Cite

Cisplatin, a platinum compound, is used as a first-line agent against various forms of solid cancers. Nephrotoxicity is an important adverse effect of cisplatin therapy, which involves increased oxidative stress, inflammation, apoptosis, and activation of the mitogen-activated protein kinase (MAPK) pathway. It is well known that the bioactive compounds present in green tea are used to treat various disorders due to their biological activities. With this background, the present study was aimed to investigate the effect of epicatechin gallate (ECG), a green tea polyphenol, in cisplatin-induced nephrotoxicity in rats. To achieve this, ECG (1.25, 2.5, and 5 mg/kg; intraperitoneal (i.p.)) was administered to male albino Wistar rats for the period of 10 days. On the 7th day, a single i.p. injection of cisplatin (8 mg/kg) was injected into rats to produce kidney injury and the animals were then killed on the 10th day. Cisplatin toxicity was associated with enhanced oxidative stress, impaired renal function along with marked tubular necrosis in Histopathology. Furthermore, cisplatin activated the MAPK pathway, which contributed to inflammation and apoptosis in the kidney of treated rats. In contrast, ECG (5 mg/kg) pretreatment normalized cisplatin-induced oxidative stress, renal function, and histopathological changes. ECG also prevented the activation of the MAPK pathway, and attenuated inflammation and apoptosis in rats. These findings suggest that ECG prevented cisplatin-induced oxidative stress, inflammation, and apoptosis by downregulating the MAPK pathway and resulted in improved renal function.

show abstract

Section: Discussionsupporting

confidence: 59%

Molecular mechanisms underlying attenuation of cisplatin-induced acute kidney injury by epicatechin gallate

Malik

Suchal

Bhatia

et al. 2016

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…Similarly, Nowak et al demonstrated that inhibition of ERK1/2, kinases that are activated following phosphorylation by MEK1/2, attenuated CP-induced caspase-3 activity and apoptosis in cultured renal proximal tubular cells [36]. Moreover, some previous in vitro studies indicated that U0126 reduced Bax activation and decreased the Bax/Bcl-2 ratio [35], [37]. Those reports are consistent with our results, in which we confirmed that erlotinib significantly attenuated the CP-induced phosphorylation of MEK1 in tubular epithelial cells.…”

Section: Discussionmentioning

confidence: 91%

“…Previously, it has been reported that not only ERK1/2 but also MEK1/2 are deeply involved in CP-induced tubular cell apoptosis [4], [33], [34]. The roles of p38 and Jun N-terminal kinase, which also consist of the MAPK pathway, are less clear in CP-induced tubular cell apoptosis [4], [35]. Jo et al demonstrated that a MEK inhibitor, U0126, attenuated CP-N by decreasing tubular cell apoptosis in mice [34].…”

Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor Receptor Inhibition with Erlotinib Partially Prevents Cisplatin-Induced Nephrotoxicity in Rats

et al. 2014

View full text Add to dashboard Cite

The effects of blocking the epidermal growth factor receptor (EGFR) in acute kidney injury (AKI) are controversial. Here we investigated the renoprotective effect of erlotinib, a selective tyrosine kinase inhibitor that can block EGFR activity, on cisplatin (CP)-induced AKI. Groups of animals were given either erlotinib or vehicle from one day before up to Day 3 following induction of CP- nephrotoxicity (CP-N). In addition, we analyzed the effects of erlotinib on signaling pathways involved in CP-N by using human renal proximal tubular cells (HK-2). Compared to controls, rats treated with erlotinib exhibited significant improvement of renal function and attenuation of tubulointerstitial injury, and reduced the number of apoptotic and proliferating cells. Erlotinib-treated rats had a significant reduction of renal cortical mRNA for profibrogenic genes. The Bax/Bcl-2 mRNA and protein ratios were significantly reduced by erlotinib treatment. In vitro, we observed that erlotinib significantly reduced the phosphorylation of MEK1 and Akt, processes that were induced by CP in HK-2. Taken together, these data indicate that erlotinib has renoprotective properties that are likely mediated through decreases in the apoptosis and proliferation of tubular cells, effects that reflect inhibition of downstream signaling pathways of EGFR. These results suggest that erlotinib may be useful for preventing AKI in patients receiving CP chemotherapy.

show abstract

“…Although cisplatin is one of the most remarkable anticancer drugs, its use is limited by severe side effects in normal tissues including neurotoxicity and nephrotoxicity, with an incidence of approximately 33% (Ries and Klastersky, 1986;Park et al, 2013). Several renoprotective approaches have been introduced such as inhibition of cisplatin uptake (Ciarimboli et al, 2005), inhibition of oxidative stress (Gao et al, 2013), and modulation of cell death pathways (Park et al, 2002). Inhibiting these cisplatin mechanisms leads to some renoprotection, suggesting a combination of strategies is necessary.…”

Section: Discussionmentioning

confidence: 99%

Fenofibrate reduces cisplatin-induced apoptosis of renal proximal tubular cells via inhibition of JNK and p38 pathways

et al. 2016

View full text Add to dashboard Cite

-Cisplatin is widely used as a standard chemotherapy for solid tumors. The major adverse effect of cisplatin is nephrotoxicity in proximal tubular cells, via oxidative stress, DNA damage, cell apoptosis, and inflammation. The aim of this study was to investigate the pharmacological effect and mechanism of fibrate drugs on cisplatin-induced renal proximal tubular cell death. Cisplatin decreased cell viability of LLC-PK1 and HK-2 cells in a dose-dependent manner. Cisplatin-induced apoptosis was attenuated by co-treatment with fenofibrate while less so with clofibrate and bezafibrate. Fenofibrate's protective effect was not complimented by co-treatment with GW6471, a PPARα antagonist, indicating the protective effect occurred via a PPARα-independent mechanism. Treating cells with cisplatin induced reactive oxygen species (ROS), c-JUN N-terminal kinase (JNK), and p38 kinase (p38), but not extracellular signal-regulated kinase (ERK). Fenofibrate reversed cisplatin-induced JNK and p38 activation, but had no effect on ROS production. The findings suggest fenofibrate's protective effect on cisplatin-induced cytotoxicity is mediated by inhibition of JNK and p38. Moreover, fenofibrate did not alter cisplatin's antitumor effect on cancer cell lines including T84, SW-480, HepG2, and SK-LU-1 cells. Therefore, fenofibrate may be a candidate agent for further development as an adjuvant to cisplatin treatment.

show abstract

Cyanidin reverses cisplatin-induced apoptosis in HK-2 proximal tubular cells through inhibition of ROS-mediated DNA damage and modulation of the ERK and AKT pathways

Cited by 68 publications

References 38 publications

Molecular mechanisms underlying attenuation of cisplatin-induced acute kidney injury by epicatechin gallate

Molecular mechanisms underlying attenuation of cisplatin-induced acute kidney injury by epicatechin gallate

Epidermal Growth Factor Receptor Inhibition with Erlotinib Partially Prevents Cisplatin-Induced Nephrotoxicity in Rats

Fenofibrate reduces cisplatin-induced apoptosis of renal proximal tubular cells via inhibition of JNK and p38 pathways

Contact Info

Product

Resources

About