scholarly journals A Novel Polyhalogenated Monoterpene Induces Cell Cycle Arrest and Apoptosis in Breast Cancer Cells

Marine Drugs ◽  
2019 ◽  
Vol 17 (8) ◽  
pp. 437 ◽  
Author(s):  
Menna El Gaafary ◽  
Susanne Hafner ◽  
Sophia J. Lang ◽  
Lu Jin ◽  
Omar M. Sabry ◽  
...  

Breast cancer is the most common cancer type and a primary cause of cancer mortality among females worldwide. Here, we analyzed the anticancer efficacy of a novel bromochlorinated monoterpene, PPM1, a synthetic analogue of polyhalogenated monoterpenes from Plocamium red algae and structurally similar non-brominated monoterpenes. PPM1, but not the non-brominated monoterpenes, decreased selectively the viability of several triple-negative as well as triple-positive breast cancer cells with different p53 status without significantly affecting normal breast epithelial cells. PPM1 induced accumulation of triple-negative MDA-MB-231 cells with 4N DNA content characterized by decreased histone H3-S10/T3 phosphorylation indicating cell cycle arrest in the G2 phase. Western immunoblot analysis revealed that PPM1 treatment triggered an initial rapid activation of Aurora kinases A/B/C and p21Waf1/Cip1 accumulation, which was followed by accumulation of polyploid >4N cells. Flow cytometric analysis showed mitochondrial potential disruption, caspase 3/7 activation, phosphatidylserine externalization, reduction of the amount polyploid cells, and DNA fragmentation consistent with induction of apoptosis. Cell viability was partially restored by the pan-caspase inhibitor Z-VAD-FMK indicating caspase contribution. In vivo, PPM1 inhibited growth, proliferation, and induced apoptosis in MDA-MB-231 xenografted onto the chick chorioallantoic membrane. Hence, Plocamium polyhalogenated monoterpenes and synthetic analogues deserve further exploration as promising anticancer lead compounds.

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Samia Shoukry Messeha ◽  
Najla Omar Zarmouh ◽  
Abrar Mohamed Asiri ◽  
Karam Farah Soliman

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