Zingerone Suppresses Tumor Development through Decreasing Cyclin D1 Expression and Inducing Mitotic Arrest

Abstract

Cancer cells undergo uncontrolled proliferation resulting from aberrant activity of various cell-cycle proteins. Therefore, despite recent advances in intensive chemotherapy, it is difficult to cure cancer completely. Recently, cell-cycle regulators became attractive targets in cancer therapy. Zingerone, a phenolic compound isolated from ginger, is a nontoxic and inexpensive compound with varied pharmacological activities. In this study, the therapeutic effect of zingerone as an anti-mitotic agent in human neuroblastoma cells was investigated. Following treatment of BE(2)-M17 cells with zingerone, we performed a 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and colony-formation assay to evaluate cellular proliferation, in addition to immunofluorescence cytochemistry and flow cytometry to examine the mitotic cells. The association of gene expression with tumor stage and survival was analyzed. Furthermore, to examine the anti-cancer effect of zingerone, we applied a BALB/c mouse-tumor model using a BALB/c-derived adenocarcinoma cell line. In human neuroblastoma cells, zingerone inhibited cellular viability and survival. Moreover, the number of mitotic cells, particularly those in prometaphase, increased in zingerone-treated neuroblastoma cells. Regarding specific molecular mechanisms, zingerone decreased cyclin D1 expression and induced the cleavage of caspase-3 and poly (ADP-ribose) polymerase 1 (PARP-1). The decrease in cyclin D1 and increase in histone H3 phosphorylated (p)-Ser10 were confirmed by immunohistochemistry in tumor tissues administered with zingerone. These results suggest that zingerone induces mitotic arrest followed by inhibition of growth of neuroblastoma cells. Collectively, zingerone may be a potential therapeutic drug for human cancers, including neuroblastoma.

Anti‑angiogenic and anti‑proliferative effects of Benja‑ummarit extract in rats with hepatocellular carcinoma

“…The anti-proliferative property of a crude extract of BU has been ascribed to much the same components as its anti-angiogenic effects, including gambogic acid in gamboge resin (13,16,45), aloe-emodin in aloe vera (46,47), galbanic acid in asafetida (39), 6-gingerol or zingerone in ginger (40,41,48,49), piplartine in Javanese long pepper (50) and piperine in black pepper (51-55). 6-Gingerol or zingerone in ginger reportedly inhibits cell proliferation via cell cycle arrest at the G1 phase (40) via the downregulation of cyclin D1 expression (48,49) or inhibition of nuclear factor-κβ activation (41). Similarly, piperine in black pepper may induce cell cycle arrest via the downregulation of cyclin D1 (51,52,54).…”

Zingiberis Rhizoma Recens: A Review of Its Traditional Uses, Phytochemistry, Pharmacology, and Toxicology

“…Additionally, zingerone, one of the major active phenolic agents of ZRR, significantly reduced cell viability, improved the production of reactive oxygen species, and induced apoptosis of breast cancer cell line MCF-7 [ 79 ]. Zingerone reduced the expression of cyclin D1, induced the cleavage of caspase-3 and PARP-1, which arrested mitosis, thereby inhibiting the growth of human neuroblastoma cells [ 80 ].…”

Therapeutic potential of Zingiberaceae in Alzheimer's disease

“…Z. officinale is the most common spice and fresh plant used worldwide (Choi et al, 2018). It is broadly known for its rhizomes, important sources of phytonutrients, with characteristic aroma and spicy taste, widely used in beverages and food (Mirmosayyeb et al, 2017).…”