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Simple Summary: Long non-coding RNAs (lncRNAs) exert their influence on transcriptional regulation and genome organization by associating with transcription factors, chromatin, RNAs and various proteins. In particular, studies have established a widespread involvement of cross-talks between lncRNAs and nuclear receptors (NRs) in pathology of diseases such as cancer. A deeper understanding of these cross-talks will not only help gain greater insights into cancer physiology, but also guide the development for newer and improved therapeutic strategies aimed at cancer. Long non-coding RNAs (lncRNAs) play key roles in various epigenetic and post-transcriptional events in the cell, thereby significantly influencing cellular processes including gene expression, development and diseases such as cancer. Nuclear receptors (NRs) are a family of ligand-regulated transcription factors that typically regulate transcription of genes involved in a broad spectrum of cellular processes, immune responses and in many diseases including cancer. Owing to their many overlapping roles as modulators of gene expression, the paths traversed by lncRNA and NR-mediated signaling often cross each other; these lncRNA-NR cross-talks are being increasingly recognized as important players in many cellular processes and diseases such as cancer. Here, we review the individual roles of lncRNAs and NRs, especially growth factor modulated receptors such as androgen receptors (ARs), in various types of cancers and how the cross-talks between lncRNAs and NRs are involved in cancer progression and metastasis. We discuss the challenges involved in characterizing lncRNA-NR associations and how to overcome them. Furthering our understanding of the mechanisms of lncRNA-NR associations is crucial to realizing their potential as prognostic features, diagnostic biomarkers and therapeutic targets in cancer biology. [ABSTRACT FROM AUTHOR]

Flavonoids are polyphenolic phytochemicals, which occur naturally in plants and possess both anti-oxidant and pro-oxidant properties. Flavonoids are gaining increasing popularity in the pharmaceutical industry as healthy and cost-effective compounds. Flavonoids show beneficial pharmacological activities in the treatment and prevention of various types of diseases. They are natural and less toxic agents for cancer chemotherapy and radiotherapy via regulation of multiple cell signaling pathways and pro-oxidant effects. In this review, we have summarized the mechanisms of action of selected flavonoids, and their pharmacological implications and potential therapeutic applications in cancer therapy. [ABSTRACT FROM AUTHOR]

Purpose: Radiobiological research continues to focus on finding newer strategies for enhanced killing of tumor cells by ionizing radiation. In recent years, chemotherapeutic drugs have been found to possess the capabilities to sensitize tumor cells without affecting the normal cells. There have been increasing research efforts to identify novel and nontoxic compounds which cause minimal or no harm to normal cells but maximize tumor toxicity response to radiation exposure. Extensive researches on flavonoids that are compounds derived from plants have shown that these have promising abilities as radioprotectors and radiosensitizers. Conclusions: In this review, we examine the role of flavonoids as potential radiosensitizers, review the underlying molecular mechanisms and discuss their potential usefulness in improving cancer radiotherapy. It is emphasized that obtaining a deeper insight into the molecular mechanisms underlying the combined action of flavonoids and ionizing radiation may provide new directions for radiobiological research applicable to the much needed enhanced selective tumor cytotoxicity to treatment agents. [ABSTRACT FROM AUTHOR]

Byline: Prabha Tiwari, S. Balakrishnan, S. Kannan, H.S. Kushwaha, K.P. Mishra The major biological consequences of ionising radiation are generally attributed to the generated free radicals and their reactions with vital cellular components. The level of antioxidants in irradiated cells and animals is generally considered an important determinant of radiobiological damage. The present study aimed to investigate the effect of antioxidants of the thiol family, namely, N-acetyl cysteine (NAC), glutathione (GSH) and thioproline (TP) on the radiation-induced chromosomal damage in human lymphocytes in vitro. The incidence of micronucleus (MN) formation, as measured by the cytochalasin B method, was found to be dependent on low to moderate radiation doses (0-200 cGy). The frequency of MN formation in lymphocytes pretreated with antioxidants was found to decrease with their concentration (100-300 μM). The results show that GSH was a more effective protector than NAC or TP, possibly due to relative radical scavenging efficiency. It was further found that treatment with equimolar concentrations of combined NAC and GSH yielded the most effective reduction in MN frequency compared to other combinations of NAC-TP and GSH-TP. The results suggest that the pretreatment of blood with thiol antioxidants significantly prevented MN formation in the isolated lymphocytes. These results may help in developing protocols for effective protectors against radiation exposure for practical applications.

Silibinin, a natural flavonoid, under phase I/II clinical trial in prostate cancer patients was aimed to evaluate its chemotherapeutic potential in human breast cancer cell MCF7 and T47D. Results showed that T47D cells were found to be more sensitive to silibinin than MCF7 as observed by proliferation, clonogenic, and apoptotic assays, which was abrogated by pan-caspase inhibitor but remained unaffected by p53 inhibitor. Apoptotic events in both cell types differ temporally and also by magnitude that involved mitochondrial and caspase-8 activation pathway. These results have relevance in understanding silibinin treatment to breast tumor. [ABSTRACT FROM AUTHOR]