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d ‐Carvone inhibits the JAK/STAT3 signaling pathway and induced the apoptotic cell death in the human gastric cancer AGS cells
Author(s) -
Lv Long,
Yang Nan,
Cao Youhong,
Dang Junqiang,
Cheng Likun,
ElSheikh Mohamed A.,
Zhang Yun
Publication year - 2021
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22746
Subject(s) - propidium iodide , apoptosis , signal transduction , cancer cell , reactive oxygen species , chemistry , stat3 , programmed cell death , cancer , biology , cancer research , biochemistry , genetics
Globally, gastric cancer is one of the leading cause of death. Surgical and chemotherapy constitute an important treatment regimen. Unfortunately, less than 20 persons out of 100 patients are live on almost 5 years. Hence, a nontoxic, effective and significantly enhancing novel therapeutic agent is required. d ‐Carvone is a natural terpenoid present in the essential oils and abundant in the seeds of caraway, as well as known folk medication for diarrhea, acidity, and other gastric disorders. Nevertheless, the role of d ‐carvone on gastric cancer and its underlying molecular mechanism resides enigmatic. Cells were treated with d ‐carvone to find out the IC 50 by MTT assay. This study shows that 20 and 25 μM d ‐carvone has induced the reactive oxygen species production and mitochondrial membrane potential in gastric cancer AGS cells, which were evaluated by 2,7‐dichlorofluoresceindiacetate and Rh123 staining methods, respectively. The effect of d ‐carvone against the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway was studied through immunoblotting. Then, we found that it effectively inhibited the proliferation of cell, and the induction of cell apoptosis was scrutinized by dual, 4’,6‐diamidino‐2‐phenylindole, and also propidium iodide staining methods. We also explored the fundamental molecular signaling mechanism of the d ‐carvone and our data depicts that d ‐carvone induced apoptosis cell death by mitochondrial reactive oxygen species production and downregulation of the and JAK and STAT3 signaling molecules. These overall findings support that the d ‐carvone inhibits the JAK/STAT3 signaling pathway and induces cell death in the gastric cancer AGS cells.