Schizandrin B inhibits the cis‑DDP‑induced apoptosis of HK‑2 cells by activating ERK/NF‑κB signaling to regulate the expression of survivin

Abstract

The nephrotoxicity of cisplatin limits its clinical application. Schizandrin B (SchB) has been demonstrated to have a variety of potential cytoprotective activities. The present study explored the molecular mechanisms by which SchB inhibits the dichlorodiammine platinum (DDP)-induced apoptosis of HK-2 proximal tubule epithelial cells. In vitro assays demonstrated that SchB increased the viability of HK-2 cells, alleviated the cis-DDP-induced activation of caspase-3, reduced apoptosis and improved the nuclear morphology of HK-2 cells. Additionally, the mechanism underlying the cis-DDP-induced apoptosis was indicated to involve the activation of p53, c-Jun-N-terminal kinase (JNK) and p38 signaling. Furthermore, SchB was demonstrated to activate extracellular signal-regulated kinase (ERK) and nuclear factor κB (NF-κB) signaling, and induce the expression of survivin. The inhibition of ERK and NF-κB signaling using U0126 and pyrollidine dithiocarbamate, respectively, inhibited the expression of survivin, whereas blocking the expression of survivin using small interfering RNA inhibited the alleviating effect of SchB on cis-DDP-induced apoptosis as indicated by a reduction in cleaved caspase-3 expression. In conclusion, SchB regulates ERK/NF-κB signaling to induce the expression of survivin, thereby alleviating cis-DDP-induced renal injury.

RETRACTED: Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF Pathway

“…It has been extensively utilized to cure different types of neoplasms, including head and neck ( 9 , 10 ), lung ( 11 , 12 ), ovarian ( 13 , 14 ), breast ( 15 , 16 ), brain ( 17 , 18 ), kidney ( 19 , 20 ), and esophagus cancers ( 21 – 23 ). In general, DDP and other platinum-based compounds are considered to be cytotoxic drugs, which can induce apoptosis of cancer cells ( 24 ). Numerous molecular anticancer mechanisms have been described, including the induction of p53 signaling and cell cycle arrest ( 25 , 26 ), downregulation of proto-oncogenes and anti-apoptotic proteins, and activation of both intrinsic and extrinsic apoptosis ( 27 , 28 ).…”

Natural products: potential treatments for cisplatin-induced nephrotoxicity

“…Natural products types Representative natural products [120,121]. It is believed that Schisandra sphenanthera extract facilitates the nuclear accumulation of the transcription factor NRF2 to mitigate cisplatin-induced nephrotoxicity, which is important for therapeutic approaches to AKI [122].…”

Schisandrin B Inhibits Cell Viability and Migration, and Induces Cell Apoptosis by circ_0009112/miR-708-5p Axis Through PI3K/AKT Pathway in Osteosarcoma

“…For instance, Ran et al evaluated that Sch B alleviated osteoarthritis by repressing NF-κB and MAPK pathways ( Ran et al, 2018 ). Liu et al (2018) explained that dichlorodiammine platinum (DDP) promoted cell apoptosis, whereas Sch B repressed this effect by regulating ERK/NF-κB pathway. Our data showed that Sch B exposure downregulated the expression of PI3K/AKT pathway-related proteins (p-PI3K and p-AKT), which meant that Sch B regulated osteosarcoma progression by blocking PI3K/AKT signaling pathway.…”