Zosterabisphenone B, a new diarylheptanoid heterodimer from the seagrass Zostera marina, induces apoptosis cell death in colon cancer cells and reduces tumour growth in mice

被引:0
|
作者
Cacciola, Nunzio Antonio [1 ]
De Cicco, Paola [2 ]
Amico, Rebecca [2 ]
Sepe, Fabrizia [3 ]
Li, Yan [4 ]
Grauso, Laura [5 ]
Nani, Maria Francesca [2 ]
Scarpato, Silvia [2 ]
Zidorn, Christian [6 ]
Mangoni, Alfonso [2 ]
Borrelli, Francesca [2 ]
机构
[1] Univ Naples Federico II, Dept Vet Med & Anim Prod, Naples, Italy
[2] Univ Naples Federico II, Sch Med & Surg, Dept Pharm, Naples, Italy
[3] Natl Res Council CNR, Inst Expt Endocrinol & Oncol G Salvatore IEOS, Naples, Italy
[4] Chinese Acad Sci, Dalian Inst Chem Phys, Key Lab Separat Sci Analyt Chem, Dalian, Peoples R China
[5] Univ Naples Federico II, Dept Agr Sci, Naples, Italy
[6] Christian Albrechts Univ Kiel, Pharmazeut Inst, Abt Pharmazeut Biol, Kiel, Germany
关键词
apoptosis; autophagy; colorectal cancer; marine compounds; phytochemicals; xenografts; PATHWAYS;
D O I
10.1002/ptr.8269
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Colorectal cancer (CRC) is one of the most common malignant tumours worldwide. Diarylheptanoids, secondary metabolites isolated from Zostera marina, are of interest in natural products research due to their biological activities. Zosterabisphenone B (ZBP B) has recently been shown to inhibit the viability of CRC cells. The aim of this study was to investigate the therapeutic potential of ZBP B for targeting human CRC cells. Cell viability was determined using the MTT assay. Flow cytometry and Western blot analyses were used to assess apoptosis and autophagy. A CRC xenograft model was used to evaluate the in vivo effect of ZBP B. No cytotoxic effect on HCEC cells was observed in the in vitro experiments. ZBP B caused morphological changes in HCT116 colon cancer cells due to an increase in early and late apoptotic cell populations. Mechanistically, ZBP B led to an increase in cleaved caspase-3, caspase-8, caspase-9, PARP and BID proteins and a decrease in Bcl-2 and c-Myc proteins. In the xenograft model of CRC, ZBP B led to a reduction in tumour growth. These results indicate that ZBP B exerts a selective cytotoxic effect on CRC cells by affecting apoptotic signalling pathways and reducing tumour growth in mice. Taken together, our results suggest that ZBP B could be a lead compound for the synthesis and development of CRC drugs.
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页码:4168 / 4176
页数:9
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