Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04
  • 2024-05
  • 2024-06
  • 2024-07
  • In this report the natural

    2024-07-09

    In this report, the natural compound deguelin potently and dose-dependently suppressed Aurora B kinase activity in vitro, indicating that this compound is an effective Aurora B inhibitor. The docking study indicated that deguelin was docked into the ATP-binding pocket of Aurora B and formed hydrophobic interactions with Phe172, Leu223, Leu154, etc. In addition, deguelin had no obvious effect on Aurora A activity at the same concentration (Fig. S4). Previous studies have demonstrated that the predominant response of tumor Dimethyl Fumarate to Aurora B inhibitor treatment was aborted cell division without a protracted mitotic arrest, inducing the formation of polyploidy cell and resulting in polyploidy-specific lethality or senescence (Payton et al., 2010, Sadaie et al., 2015). Our results showed that deguelin inhibited the anchorage-dependent and -independent growth of human ESCC cells. Treatment with deguelin induced accumulation of G2/M cells, polyploidy cell formation, and apoptosis, which is consistent with Aurora B inhibition. In addition, knockdown of Aurora B decreases the sensitivity of ESCC cells to deguelin, which agrees with our observations that Aurora B plays an important role in the anticancer activity of deguelin. Moreover, our in vivo study also demonstrated that deguelin significantly decreased tumor growth and down-regulated phosphorylated Histone-H3 staining without obvious cytotoxic effect. Esophageal carcinoma is often refractory to current therapeutic approaches and has a poor prognosis. The incidence of esophageal carcinoma is closely linked to geographic region and racial background. During the past few decades, the incidence of adenocarcinoma which arises in the esophagogastric junction or distal esophagus has increased considerably in western countries, whereas in China and other Asian nations, such as Japan, over 90% of all Dimethyl Fumarate esophageal carcinomas are squamous-cell carcinomas (Abnet et al., 2017, Lagergren and Lagergren, 2013, Rice et al., 2017). Although ESCC can be treated with various techniques, including chemotherapy, radiotherapy, and endoscopy, the surgical resection has remained the mainstay of treatment. Currently, attention has focused on the role of targeted agents in the treatment of various types of cancer. Studies of targeted agents for ESCC have just begun. Although the combination of EGFR targeted therapy agent cetuximab and radiotherapy in ESCC patients obtained a clinical complete response rate of 70%, more evidence is needed to prove that adding cetuximab to preoperative chemoradiotherapy is feasible without increasing postoperative mortality (Enzinger et al., 2016). Previous studies indicated that Aurora A is highly expressed in ESCC (Tamotsu et al., 2015, Tong et al., 2004), whereas the status of Aurora B in ESCC is not clear. In the present study, we found that Aurora B is overexpressed in ESCC cell lines, and the high levels of Aurora B protein were associated with worse overall survival rate. Moreover, knockdown Aurora B in human ESCC cells reduced tumorigenic properties, including in vitro cell growth and in vivo xenografted tumor formation. All of this evidence suggested that the development of Aurora kinases targeted therapy may serve as a selective strategy for clinical ESCC treatment. Recently, a growing number of inhibitors of Aurora kinases have been developed for both hematopoietic malignancies and solid tumors, either at preclinical or clinical stages (Ashton et al., 2016, Dar et al., 2010, Floc'h et al., 2017). Previous studies have demonstrated that the Aurora B specific inhibitor, AZD1152, significantly suppressed human solid tumors, including prostate (Zekri et al., 2017), lung (Helfrich et al., 2016), breast (Larsen et al., 2015) cancer and nasopharyngeal carcinoma (Li et al., 2015). However, the antitumor effect of Aurora B kinase inhibitors against ESCC is still elusive. Our study clearly showed that deguelin-induced ESCC growth inhibition was dependent on deguelin-mediated Aurora B activity suppression because down-regulation of Aurora B significantly decreased the sensitivity of ESCC cells to deguelin treatment. Our results are in agreement with those recent publications that the Aurora B specific inhibitor also exerts the potent anti-tumor effect in solid tumors.