Anticancer genes (NOXA, PAR-4, TRAIL) are de-regulated in breast cancer patients and can be targeted by using a ribosomal inactivating plant protein (riproximin)

Abstract

Abstract Background: Anticancer genes are endogenous enemies of transformed cells and impose antineoplastic effects upon ectopic expression. Identifying the expression profile of these genes is a prerequisite to explore their prognostic and therapeutic relevance in cancers. In parallel, natural compounds can be explored for their ability to upregulate anticancer genes in malignant cells for therapeutic purposes. In this study, we identified the expression levels of anticancer genes in breast cancer clinical isolates. In addition, the potential of a purified and sequenced plant protein (riproximin) to induce anticancer genes in breast cancer cells was evaluated. Methodology:Expression profiles of three anticancer genes (NOXA, PAR-4, TRAIL) were identified by immunohistochemistry in 45 breast cancer clinical isolates. Effects of riproximin exposure on expression of the anticancer genes were explored via microarray, real-time PCR and western blot methodologies. Lastly, the bioinformatic approach was adopted to highlight the molecular/functional significance of the anticancer genes. Results:NOXA expression was evenly de-regulated among the clinical isolates, while PAR-4 was significantly down-regulated in majority of the breast cancer tissues. In contrast, a higher TRAIL expression was observed in most of the clinical samples. Expression levels of the anticancer genes were following a distinct trend in accordance with the disease severity. Riproximin showed a substantial potential of inducing the anticancer genes in breast cancer cells at transcriptomic and protein levels. The bioinformatic approach revealed involvement of anticancer genes in multiple cellular functions and signaling cascades. Conclusion:Anticancer genes were de-regulated and showed discrete expression patterns in breast cancer patient samples. Riproximin effectively induced the expression of selected anticancer genes in breast cancer cells.