Abstract
Background
Riproximin, a type II ribosome-inactivating protein (RIP), has shown significant cytotoxic effects in diverse types of cancer cells. To better understand its therapeutic potential, elaborated investigations on the mechanistic aspects of riproximin deem crucial. In this study, we focused on riproximin-mediated changes in cellular properties and corresponding molecular pathways in breast cancer cells.
Methods
Cytotoxicity of riproximin was determined by MTT assay, while the clonogenic and migratory effects were determined by colony formation, migration, and scratch assays. Cytostatic and apoptotic effects were studied by flow cytometry and nuclear staining procedures. Alterations at molecular levels were scrutinized by means of microarray and qRT-PCR methodologies.
Results
Riproximin induced significant cytotoxic effects in the selected human breast cancer cells MDA-MB-231 and MCF-7. Profound inhibition of migration and colony formation were observed in both cell lines in response to riproximin exposure. Concomitantly, a significant arrest in S phase and nuclear fragmentation were observed as causes for its cytostatic and apoptotic effects, respectively. Genetic profiling revealed pronounced induction of the anticancer cytokine IL24/MDA-7 and ER-stress-related GADD genes. In addition, prominent inhibition of the genes relevant to migration (RHO GTPases), anti-apoptotic activities (BCL family), and cell cycle (cyclins) was also noticed.
Conclusion
Riproximin, with its significant antineoplastic effects, modulates multiple cytostatic and apoptotic pathways in breast cancer cells. Results from these investigations highlight the future therapeutic potential of this naturally occurring compound for breast cancer.
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This study was funded by a stipendium of HEC (HEC; Higher Education Commission, Pakistan) to one of the authors (A. P; Grant Number 91549644).
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Pervaiz, A., Zepp, M., Adwan, H. et al. Riproximin modulates multiple signaling cascades leading to cytostatic and apoptotic effects in human breast cancer cells. J Cancer Res Clin Oncol 142, 135–147 (2016). https://doi.org/10.1007/s00432-015-2013-3
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DOI: https://doi.org/10.1007/s00432-015-2013-3