Abstract
BackgroundLapachol is a natural naphthoquinone compound that possesses extensive biological activities. The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vivo, as well as the potential mechanisms.MethodsThe antitumor effect of lapachol was firstly evaluated in the C6 glioma model in Wistar rats. The effects of lapachol on C6 cell proliferation, apoptosis and DNA damage were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS)/ phenazinemethosulfate (PMS) assay, hoechst 33358 staining, annexin V-FITC/PI staining, and comet assay. Effects of lapachol on topoisomerase I (TOP I) and topoisomerase II (TOP II) activities were detected by TOP I and TOP II mediated supercoiled pBR322 DNA relaxation assays and molecular docking. TOP I and TOP II expression levels in C6 cells were also determined.ResultsHigh dose lapachol showed significant inhibitory effect on the C6 glioma in Wistar rats (P < 0.05). It was showed that lapachol could inhibit proliferation, induce apoptosis and DNA damage of C6 cells in dose dependent manners. Lapachol could inhibit the activities of both TOP I and II. Lapachol-TOP I showed relatively stronger interaction than that of lapachol-TOP II in molecular docking study. Also, lapachol could inhibit TOP II expression levels, but not TOP I expression levels.ConclusionThese results showed that lapachol could significantly inhibit C6 glioma both in vivo and in vitro, which might be related with inhibiting TOP I and TOP II activities, as well as TOP II expression.
Highlights
Lapachol is a natural naphthoquinone compound that possesses extensive biological activities
We have previously studied the in vivo lapachol metabolism using a sensitive LC-ESI–MSn method [17], and found that lapachol was able to cross the blood brain barrier, indicating that it might be effective in treating malignant glioma
Lapachol could decrease tumor volumes without affecting the body weights of glioma-bearing rats MRI, hematoxylin/ eosin (HE) and immunohistochemical staining were used to confirm the successful establishment of the rat C6 glioma model
Summary
Lapachol is a natural naphthoquinone compound that possesses extensive biological activities. Temozolomide (TMZ), an oral DNA-alkylating agent that can cross the bloodbrain barrier, is the major chemotherapeutic drug used in clinical for the treatment of malignant gliomas [2]. Malignant glioma cells quickly develop TMZ resistance and the long-term clinical benefits of TMZ are poor [3]. Developing new drugs that can Naphthoquinone is an important class of naturally occurring active ingredients with unique physical and chemical properties and pharmacological effects [4]. They are widely used as anticarcinogenic, antibacterial, antimalarial, and fungicidal agents [5]. The cytotoxicity of lapachol and its derivatives were evaluated in many tumor cells, such as oesophageal cancer cells [8], Ehrlich’s carcinoma [9], Xu et al Journal of Experimental & Clinical Cancer Research (2016) 35:178
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
