Cryptotanshinone induces reactive oxygen species‑mediated apoptosis in human rheumatoid arthritis fibroblast‑like synoviocytes

Abstract

The present study investigated the mechanisms of apoptosis induced by cryptotanshinone (CT) in human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). Cell Counting kit-8 assay was performed to determine the cytotoxic effects of CT in human RA-FLSs, including primary RA-FLS, HFLS-RA and MH7A cells, and in HFLS cells derived from normal synovial tissue. Annexin V-FITC/PI staining was used to detect the apoptotic effects of CT in HFLS-RA and MH7A cells. Flow cytometry was performed to detect the apoptotic and reactive oxygen species (ROS) levels induced by CT in HFLS-RA cells. Western blotting was used to assess the expression levels of proteins associated with apoptosis and with the mitogen-activated protein kinase (MAPK), protein kinase B (Akt), and signal transducer and activator of transcription-3 (STAT3) signaling pathways. The results demonstrated that CT treatment significantly suppressed HFLS-RA and MH7A cell growth, whereas no clear inhibitory effect was observed in normal HFLS cells. CT exposure downregulated the expression levels of B-cell lymphoma 2 (Bcl-2), p-Akt, p-extracellular signal-related kinase and p-STAT3, while it upregulated the expression levels of Bcl-2-associated death promoter (Bad), caspase-3, poly (ADP-ribose) polymerase (PARP), p-p38 and p-c-Jun N-terminal kinase. Following ROS scavenging, the CT-induced apoptosis and altered expression levels of Bcl-2, Bad, cleaved caspase-3 and cleaved PARP were restored. Furthermore, the Akt, MAPK and STAT3 signaling pathways were regulated by intracellular ROS. These results suggest that ROS-mediated Akt, MAPK and STAT3 signaling pathways serve important roles in the CT-induced apoptosis of RA-FLSs.

Uncovering the Mechanisms of Cryptotanshinone as a Therapeutic Agent Against Hepatocellular Carcinoma

“…Cryptotanshinone (CPT), an active compound isolated from Radix Salviae Miltiorrhizae , has been reported to possess diverse pharmacological activities, including anti-fibrosis, neuroprotective, anti-inflammatory, anti-atherosclerotic, and antioxidant activities ( Mei et al, 2009 ; Wong et al, 2010 ; Ran et al, 2016 ; Lo et al, 2017 ; Bai et al, 2019 ; Sun et al, 2019 ; Zhou et al, 2019 ). For example, CPT reduced inflammation and oxidative stress in renal interstitial fibrosis by modulating the Nrf-2/HO-1 and NF-kappaB signaling pathways ( Wang et al, 2018 ).…”

Cryptotanshinone ameliorates cardiac injury and cardiomyocyte apoptosis in rats with coronary microembolization

“…Due to these encouraging discoveries on its cardio-protective role, we assumed that CTS might have a therapeutic effect on preventing the occurrence of CME, and our results demonstrated that pretreatment of CTS for 2 weeks could effectively improve cardiac function and injury in CME rats. (Zhu et al, 2019), and CTS also reduced ROS-mediated apoptosis in human synoviocytes (Sun et al, 2019). Of note, considering that CME significantly elevated oxidative stress and cell apoptosis, both of which play important roles in the process of CME, that is why we evaluated oxidative stress and apoptosis in our study.…”

Peroxiredoxin 2 deficiency reduces white adipogenesis due to the excessive ROS generation

“…We hypothesized that the decrease in adipogenesis may be related to increased ROS‐induced adipocyte cell dysfunction in shPrx2‐3T3‐L1 cells. Several studies have reported that excessive ROS generation leads to cell death, resulting in weaken cellular functions (Hampton & O'Connor, 2016; H. N. Sun et al, 2018; F. Zhang, Xie, Munoz, Lau, & Monks, 2014). We explored the expression of markers involved in cell death after adipogenesis and found that expression levels of cleaved caspase‐3 and cleaved PARP (cell death markers) were markedly increased in shPrx2‐3T3‐L1 cells, while 3T3‐L1 cells only showed a slight increase by the 8th day (Figure 4a,b).…”