Next Article in Journal
Zinc-Chelating Mechanism of Sea Cucumber (Stichopus japonicus)-Derived Synthetic Peptides
Previous Article in Journal
Transcriptomic and Proteomic Analysis of the Tentacles and Mucus of Anthopleura dowii Verrill, 1869
Open AccessFeature PaperArticle

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

1
Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, D-89081 Ulm, Germany
2
Department of Pharmacognosy, College of Pharmacy, Cairo University, Cairo 11562, Egypt
3
Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, CA 92697-2025, USA
*
Authors to whom correspondence should be addressed.
Mar. Drugs 2019, 17(8), 437; https://doi.org/10.3390/md17080437
Received: 30 June 2019 / Revised: 17 July 2019 / Accepted: 23 July 2019 / Published: 25 July 2019
  |  
PDF [4329 KB, uploaded 25 July 2019]
  |  

Abstract

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. View Full-Text
Keywords: red algae; Plocamium; polyhalogenated monoterpenes; cell cycle; apoptosis; chick chorioallantoic membrane assay red algae; Plocamium; polyhalogenated monoterpenes; cell cycle; apoptosis; chick chorioallantoic membrane assay
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

El Gaafary, M.; Hafner, S.; Lang, S.J.; Jin, L.; Sabry, O.M.; Vogel, C.V.; Vanderwal, C.D.; Syrovets, T.; Simmet, T. A Novel Polyhalogenated Monoterpene Induces Cell Cycle Arrest and Apoptosis in Breast Cancer Cells. Mar. Drugs 2019, 17, 437.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Mar. Drugs EISSN 1660-3397 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top