MNK1 expression increases during cellular senescence and modulates the subcellular localization of hnRNP A1.

Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is an RNA-binding protein that modulates splice site usage, polyadenylation, and cleavage efficiency. This protein has also been implicated in mRNA stability and transport from the nucleus. We have previously demonstrated that hnRNP A1 had diminished protein levels and showed cytoplasmic accumulation in senescent human diploid fibroblasts. Furthermore, we have shown that inhibition of p38 MAPK, a key regulator of cellular senescence, elevated hnRNP A1 protein levels and inhibited hnRNP A1 cytoplasmic localization. In this study, we have explored the possible involvement of MNK1, one of the downstream effector of p38 MAPK, in the regulation of hnRNP A1. We have demonstrated that pharmacological inhibition of MNK1 by CGP 57380 decreased the phosphorylation levels of hnRNP A1 in young and senescent fibroblast cells and blocked the cytoplasmic accumulation of hnRNP A1 in senescent cells. In addition, MNK1 formed a complex with hnRNP A1 in vivo. The expression levels of MNK1, phospho-MNK1, and phospho-eIF4E proteins were found to be elevated in senescent cells. These data suggest that MNK1 regulates the phosphorylation and the subcellular distribution of hnRNP A1 and that MNK1 may play a role in the induction of senescence.

Dietary Isoflavones and Breast Cancer Risk.

Breast cancer is the deadliest neoplasm in women globally, resulting in a significant health burden. In many cases, breast cancer becomes resistant to chemotherapy, radiation, and hormonal therapies. It is believed that genetics is not the major cause of breast cancer. Other contributing risk factors include age at first childbirth, age at menarche, age at menopause, use of oral contraceptives, race and ethnicity, and diet. Diet has been shown to influence breast cancer incidence, recurrence, and prognosis. Soy isoflavones have long been a staple in Asian diets, and there appears to be an increase, albeit modest, compared to Asian populations, in soy consumption among Americans. Isoflavones are phytoestrogens that have antiestrogenic as well as estrogenic effects on breast cancer cells in culture, in animal models, and in clinical trials. This study will investigate anticancer and tumor promoting properties of dietary isoflavones and evaluate their effects on breast cancer development. Furthermore, this work seeks to elucidate the putative molecular pathways by which these phytochemicals modulate breast cancer risk by synergizing or antagonizing the estrogen receptor (ER) and in ER-independent signaling mechanisms.

Immunosuppressive, anti-inflammatory and anti-cancer properties of triptolide: A mini review.

OBJECTIVE: Triptolide, the active component of Tripterygium wilfordii Hook F has been used to treat autoimmune and inflammatory conditions for over two hundred years in traditional Chinese medicine. However, the processes through which triptolide exerts immunosuppression and anti-inflammation are not understood well. In this review, we discuss the autoimmune disorders and inflammatory conditions that are currently treated with triptolide. Triptolide also possesses anti-tumorigenic effects. We discuss the toxicity of various triptolide derivatives and offer suggestions to improve its safety. This study also examines the clinical trials that have investigated the efficacy of triptolide. Our aim is to examine the mechanisms that are responsible for the immunosuppressive, anti-inflammatory, and anti-cancer effects of triptolide. MATERIALS AND METHODS: The present review provides a comprehensive summary of the literature with respect to the immunosuppressive, anti-inflammatory, and anti-cancer properties of triptolide. RESULTS: Triptolide possesses immunosuppressive, anti-inflammatory, and anti-cancer effects. CONCLUSION: Triptolide can be used alone or in combination with existing therapeutic modalities as novel treatments for autoimmune disorders, cancers, and for immunosuppression.