We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Rabdocoestin B exhibits antitumor activity by inducing G2/M phase arrest and apoptosis in esophageal squamous cell carcinoma.
- Authors
Wang, Jingnan; Zhang, Zhirong; Che, Yun; Yuan, Zuyang; Lu, Zhiliang; Li, Yuan; Wan, Jun; Sun, Handong; Chen, Zhaoli; Pu, Jianxin; He, Jie
- Abstract
<bold>Purpose: </bold>Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive squamous cell carcinomas and is generally resistant to chemotherapy. In the present study, the cytotoxic activity of Rabdocoestin B (Rabd-B) against ESCC and the underlying mechanisms were investigated.<bold>Methods: </bold>The inhibitory effect of Rabd-B on KYSE30 and KYSE450 was evaluated by Cell Counting Kit-8 (CCK8) and colony formation assays in vitro. The cell cycle distribution and apoptosis of cells treated with Rabd-B were determined by flow cytometry. The mechanisms underlying the effects of Rabd-B were systematically examined by Western blot. The in vivo anti-tumor ability of Rabd-B was measured in mouse xenograft models and cisplatin (DDP) was used as positive control.<bold>Results: </bold>Rabd-B efficiently induced G2/M phase arrest in ESCC cells by upregulating the Chk1/Chk2-Cdc25C axis to inhibit the G2→M transition facilitated by Cdc2/Cyclin B1. Furthermore, Rabd-B suppressed ATM/ATR phosphorylation, thereby inhibiting BRCA1-mediated DNA repair, which resulted in mitotic catastrophe and induced cell apoptosis. Rabd-B also decreased the activity of the Akt and NF-κB survival signaling pathways and ultimately initiated the caspase-9-dependent intrinsic apoptotic pathway in ESCC cells. The apoptosis induced by Rabd-B could be partially reversed by a caspase-9-specific inhibitor (Z-LEHD-FMK) and a pan-caspase inhibitor (Z-VAD-FMK). Moreover, Rabd-B effectively suppressed tumor growth in mouse xenografts which was comparable to that of DDP without significant injuries to the mice.<bold>Conclusion: </bold>Taken together, these findings indicate that Rabd-B is a promising precursor compound that may be useful as a treatment for ESCC and thus warrants further investigation.
- Subjects
TREATMENT of esophageal cancer; SQUAMOUS cell carcinoma; CANCER chemotherapy; APOPTOSIS; ANTINEOPLASTIC agents
- Publication
Cancer Chemotherapy & Pharmacology, 2018, Vol 81, Issue 3, p469
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-017-3507-2