Ropivacaine promotes apoptosis of hepatocellular carcinoma cells through damaging mitochondria and activating caspase-3 activity

Abstract

Background Recent evidences indicated that some local anaesthetic agents played a role in inhibiting the proliferation of cancer cells; Whether ropivacaine is able to promote apoptosis of hepatocellular carcinoma (HCC) cells is still unclear. The aim of this study was to investigate the effect of ropivacaine on the apoptosis of HCC cells. Methods In the present study, we treated the HCC cell lines, Bel7402 and HLE with ropivacaine. MTT, DAPI stain, trypan blue exclusion dye assay, flow cytometry, electron microscopy, computational simulation, laser confocal microscope, Western blotting, and enzyme activity analysis of caspase-3 were applied to detect the growth and apoptosis of HCC cells and to explore the role mechanism of ropivacaine. Results Ropivacaine was able to inhibit proliferation and promote apoptosis of HCC cells in a dose- and time-dependent manner. Ropivacaine also has a trait to inhibit the migration of HCC cells; ropivacaine damaged the mitochondria of HCC cells. The results also indicated that ropivacaine was able to interact with caspase-3, promote cytoplasmic caspase-3 migration into the nucleus, stimulate cleavage of caspase-3 and PARP-1, caspase-9 proteins, inhibit the expression of Bcl-2, promote expression of Apaf-1 and mitochondria release cytochrome C, and activate the activity of caspase-3. Conclusions Ropivacaine has a novel role in promoting apoptosis of HCC cells; The role mechanism of ropivacaine maybe involve in damaging the function of mitochondria and activating the caspase-3 signalling pathway in HCC cells. Our findings provide novel insights into the local anaesthetic agents in the therapy of HCC patients. Electronic supplementary material The online version of this article (10.1186/s40659-019-0242-7) contains supplementary material, which is available to authorized users.

RASA1 inhibits the progression of renal cell carcinoma by decreasing the expression of miR-223-3p and promoting the expression of FBXW7

“…Caspases are cysteine-containing aspartate-specific hydrolases and are the primary executor of cell apoptosis [29]. Caspase-3 is a key protease in mammalian cell apoptosis and is one of the most important proteins in caspase family [30,31]. Here, we demonstrated that RASA1 could promote cell apoptosis by regulating Caspase-3 expression.…”

Ropivacaine inhibits proliferation, invasion, migration and promotes apoptosis of papillary thyroid cancer cells via regulating ITGA2 expression

“…Ropivacaine is a local anesthetic, and in recent years, more and more studies have researched on its role in tumors. Compelling evidence has indicated that Ropivacaine can induce apoptosis of hepatocellular carcinoma cells via activation of caspase-3 expression (Wang et al, 2019). Accumulating evidence has highlighted the importance of Ropivacaine in inhibition of cancers, such as breast cancer, colon cancers and gastric cancer (Castelli et al, (2020) ;Siekmann, Tina, von Sydow, & Gupta, 2019;Yang et al, 2018).…”

Repositioning Lidocaine as an Anticancer Drug: The Role Beyond Anesthesia

“…Indeed, many local anesthetics have been confirmed to possess anticancer efficacies, such as morphine ( Kim et al, 2016 ; Chen et al, 2017 ; Nishiwada et al, 2019 ), although it demonstrates contrasting results in cancer treatment ( Harper et al, 2018 ; Tuerxun and Cui, 2019 ); procaine ( Ma et al, 2016 ; Li C. et al, 2018 ; Li Y.C. et al, 2018 ); ropivacaine ( Piegeler et al, 2015 ; Gong et al, 2018 ; Wang et al, 2019 ; Yang J. et al, 2019 ); bupivacaine ( Xuan et al, 2016 ; Dan et al, 2018 ); and levobupivacaine ( Jose et al, 2018 ; Li et al, 2019 ); as well as propofol ( Xu et al, 2018 ; Kang et al, 2019 ; Zheng et al, 2019 ), etc.…”