The Antitumor Effects of Britanin on Hepatocellular Carcinoma Cells and its Real-Time Evaluation by In Vivo Bioluminescence Imaging

Abstract

Background: Hepatocellular carcinoma is a cancer with many new cases and the highest mortality rate. Chemotherapy is the most commonly used method for the clinical treatment of hepatocellular carcinoma. Natural products have become clinically important chemotherapeutic drugs due to their great potential for pharmacological development. Many sesquiterpene lactone compounds have been proven to have antitumor effects on hepatocellular carcinoma. Objective: Britanin is a sesquiterpene lactone compound that can be considered for the treatment of hepatocellular carcinoma. The present study aimed to investigate the antitumor effect of britanin. Methods: BEL 7402 and HepG2 cells were used to study the cytotoxicity and antitumor effects of britanin. Preliminary studies on the nuclear factor kappa B pathway were conducted by western blot analysis. A BEL 7402-luc subcutaneous tumor model was established for the in vivo antitumor studies of britanin. In vivo bioluminescence imaging was conducted to monitor changes in tumor size. Results: The results of the cytotoxicity analysis showed that the IC50 values for britanin in BEL 7402 and HepG2 cells were 2.702μM and 6.006μM, respectively. The results of the colony formation demonstrated that the number of cells in a colony was reduced significantly after britanin treatment. And the results of transwell migration assays showed that the migration ability of tumor cells was significantly weakened after treatment with britanin. Tumor size measurements and staining results showed that tumor size was inhibited after britanin treatment. The western blot analysis results showed the inhibition of p65 protein expression and reduced the ratio of Bcl-2/Bax after treatment. Conclusion: A series of in vitro and in vivo experiments demonstrated that britanin had good antitumor effects and provided an option for hepatocellular carcinoma treatment.

Britanin relieves ferroptosis-mediated myocardial ischaemia/reperfusion damage by upregulating GPX4 through activation of AMPK/GSK3β/Nrf2 signalling

“…Bri repressed the colony formation ability and invasion of BEL 7402 and HepG2 cells, as well as reduced the tumour size in a BEL 7402-luc subcutaneous tumour model (Li, Du, et al. 2020 ). Additionally, Bri exerted its antitumor role in gastric cancer through NF-κB-mediated immune response (Shi et al.…”

Natural Products for Liver Cancer Treatment: From Traditional Medicine to Modern Drug Discovery

“…Britanin is a sesquiterpene lactone compound that was reported to have antitumor effects on HCC [ 18 ]. The low-dose, high-dose groups of mice were injected with a britanin dose extracted from Inula linariifolia Turcz and in vivo bioluminescence imaging was conducted.…”

Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones

“…Decreasing phospho-p65 is also a means to augment the efficacy of chemotherapy [75]. Inhibition of phospho-p65 protein expression by BRT has been confirmed using BEL 7402 and HepG2 hepatocellular carcinoma cells [63]. The BRTinduced modulation of the NFκB pathway is linked to immune response.…”

“…More recently, the antitumoral activity of BRT against hepatocellular carcinoma in vivo has been confirmed using BEL-7402 cells which are more sensitive to BRT compared to HepG2 cells. BRT inhibited the migration of the tumor cells, and bioluminescence imaging revealed that the compound markedly reduced the size of tumors in mice [63].…”

“…and bioluminescence imaging revealed that the compound markedly reduced the size of tumors in mice [63].…”