Scutellarin Enhances Antitumor Effects and Attenuates the Toxicity of Bleomycin in H22 Ascites Tumor-Bearing Mice

Abstract

Bleomycin (BLM) is a broad spectrum anti-tumor drug and inducing pulmonary fibrosis. As an anti-tumor drug without immunosuppression, it is urgent to find a drug that reduces the side effects of BLM. Scutellarin (SCU), a flavone extracted from Erigeron breviscapus (Vant.) Hand-Mazz, has anti-inflammatory activity and ability to inhibit tumor cell growth, migration, and invasion. However, the combined role of SCU and BLM treatment in tumor is unclear. This study aimed to investigate the possible effect and related mechanisms of BLM combined with SCU in the treatment of tumor through in vivo and in vitro experiments. In vivo experiments showed that BLM combined with SCU in the treatment of mice bearing H22 ascites tumor prolonged the survival time, alleviated BLM-induced pulmonary fibrosis, reduced the production of TNF-α; IL-6, and the levels of MDA and MPO. BLM combined with SCU increased the apoptotic rate of H22 ascites cells and the levels of cleaved-caspases-3 and -8. Furthermore, BLM combined with SCU increased the protein expression of p53 and gene expression of miR-29b, and decreased the expression of TGF-β1. In vitro experiment results showed that BLM combined with SCU inhibited the viability of H22 cells and MRC-5 cells, promoted H22 cell apoptosis, up-regulated the protein expression of p53 and down-regulated the protein expression of α-SMA and collagen-I in MRC-5 cells. These experimental results suggested that SCU could enhance the anti-tumor effect of BLM and reduce BLM-induced pulmonary fibrosis, indicating SCU as a potential adjuvant for BLM in the future.

Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation

“…We demonstrated that scutellarin ameliorated BLM-induced pulmonary fibrosis histopathologically and through measuring α-SMA and collagen I both in vivo and in vitro. Nie et al demonstrated that scutellarin enhanced the anti-tumor effect of BLM and reduced BLM-induced pulmonary fibrosis 27 , which was consistent with our discovery. Scutellarin also plays regulatory role in fibrosis of other organ.…”

“…It was also indicated that scutellarin could exhibit protective effects in retinal hypoxia model by inhibiting NLRP3-mediated inflammatory reaction 23 . Moreover, it inhibited the neuroinflammation via the inhibition of the AKT/NF-κB and p38/JNK pathway in LPS-induced BV-2 microglial cells 26 , and enhanced anti-tumor effects and attenuated the toxicity of bleomycin in H22 ascites tumor-bearing mice 27 . However, there were no studies reported the relation between scutellarin and IPF and the efficacy of scutellarin on IPF is still largely elusive.…”

Scutellarin Attenuates the IL-1β-Induced Inflammation in Mouse Chondrocytes and Prevents Osteoarthritic Progression

“…that is often used in Chinese medicine, exhibiting a range of pharmacological and clinical activities (Wang and Ma, 2018). SCU has previously been used successfully to cardiovascular and cerebrovascular diseases (Wang et al, 2016;Wang and Ma, 2018), and it has exhibited anti-apoptotic, anti-inflammatory, and anticancer efficacy in preclinical research (Dai et al, 2011;Du et al, 2018;Nie et al, 2018). At present, however, the efficacy of SCU as a means of treating OA has not been well-studied.…”

Analysis of plasma migration components in Patrinia villosa (Thunb.) Juss. effective parts by UPLC–Q‐TOF–MS

“…The Consulting the literature showed that the phenolic acid components chlorogenic acid (Xue et al, 2017;Shao, Zhang, Chen, & Sun, 2015) and caffeic acid (Brautigan, Gielata, Heo, Kubicka, & Wilkins, 2018), and the flavonoids scutellarin (Nie et al, 2018;Sun et al, 2018;Tang & Gao, 2019), isoorientin (Huang, Jin et al, 2018;Lin et al, 2016), isovitexin (Lv, 2018), scutellarein (Jiang et al, 2018;Lu, Li, Li, & Asia, 2017;Zheng et al, 2017), luteolin (Niu, Guo, Gan, Bao, & Ren, 2015) and apigenin (Bhattacharya et al, 2018;Masuelli et al, 2017;Cai et al, 2011) had different degrees of inhibition on tumor cells. Among them, caffeic acid, isoorientin, isovitexin, luteolin and apigenin had better antiliver tumor activities.…”