bufothionine and cinobufagin

Cinobufacini is extracted from the skins and parotid venom glands of the toad for treating symptoms like swelling and pain in ancient times. Nowadays, cinobifucini injection has also achieved satisfactory therapeutic effects on hepatocellular carcinoma (HCC) in China.. Our previous work found that bufothionine, an alkaloid abundant in cinobufacini injection, induced mitochondria-mediated apoptosis. In this work, the underlying effects of bufothionine on autophagy in HCC and its possible dependent pathway were investigated.. In vitro, CCK-8 and Hoechst staining assays showed that bufothionine inhibited SMMC7721 cell proliferation and promoted apoptosis at 100 μM. In vivo, bufothionine relieved symptoms of H. This is the first report showing that bufothionine might induce autophagy in HCC by inhibiting JAK2/STAT3 pathway, presenting a possible anti-cancer mechanism of bufothionine in cinobufacini injection.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Autophagy; Bufanolides; Cell Line, Tumor; Cell Proliferation; Humans; Indole Alkaloids; Interleukin-6; Janus Kinase 2; Liver Neoplasms, Experimental; Male; Mice; Neoplasms; Quinolinium Compounds; Signal Transduction; STAT3 Transcription Factor

Cinobufacini has been traditionally used in China for the treatment of tumor since hundreds years ago. For recent years, its modern preparation,cinobifucini injection has also obtained satisfactory therapeutic functions for cancer.. High performance liquid chromatography (HPLC) analysis was applied to determine the content of cinobufagin, resibufogenin and bufothionine in cinobufacin extract liquid and injection; MTT assay and flow cytometric analysis were also respectively used to study the effect of cinobufacini extract liquid, injection and three chemical structures on cells and cell cycles.. HPLC results demonstrated that in cinobufacini extract liquid three ingredients (cinobufagin, resibufogenin and bufothionine) were all monitored while in cinofacini injection only bufothinone was detected; MTT assays showed bufothionine could obviously inhibit the proliferation of human hepatocellular carcinoma cell lines such as SMMC-7721 and BEL-7402 in a dose- and time-dependent manner as well as cinobufagin and resibufogenin; further flow cytometric analysis indicated obvious increases in G2/M phase and decrease in G0/G1 phase when SMMC-7721 cell line exposure to bufothionine (480 μg/ml).. These results suggested bufothionine could be involved in treatment of human cancer for cinobufacini injection and the mechanism might be relative to induce G2/M phase cell cycle arrest.

Topics: Amphibian Venoms; Antineoplastic Agents; Bufanolides; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Flow Cytometry; G2 Phase Cell Cycle Checkpoints; Humans; Indole Alkaloids; Injections; Liver Neoplasms; Medicine, Chinese Traditional; Quinolinium Compounds; Time Factors