Biological effects of essential oils - A review

Epithelial to mesenchymal transition (EMT) is essential for driving plasticity during development, but is an unintentional behaviour of cells during cancer progression. The EMT-associated reprogramming of cells not only suggests that fundamental changes may occur to several regulatory networks but also that an intimate interplay exists between them. Disturbance of a controlled epithelial balance is triggered by altering several layers of regulation, including the transcriptional and translational machinery, expression of non-coding RNAs, alternative splicing and protein stability.

Regulatory networks defining EMT during cancer initiation and progression

Epithelial–mesenchymal transition (EMT) is a cellular programme that is known to be crucial for embryogenesis, wound healing and malignant progression. During EMT, cell–cell and cell–extracellular matrix interactions are remodelled, which leads to the detachment of epithelial cells from each other and the underlying basement membrane, and a new transcriptional programme is activated to promote the mesenchymal fate. In the context of neoplasias, EMT confers on cancer cells increased tumour-initiating and metastatic potential and a greater resistance to elimination by several therapeutic regimens. In this Review, we discuss recent findings on the mechanisms and roles of EMT in normal and neoplastic tissues, and the cell-intrinsic signals that sustain expression of this programme. We also highlight how EMT gives rise to a variety of intermediate cell states between the epithelial and the mesenchymal state, which could function as cancer stem cells. In addition, we describe the contributions of the tumour microenvironment in inducing EMT and the effects of EMT on the immunobiology of carcinomas. Epithelial–mesenchymal transition (EMT) is crucial for embryogenesis, wound healing and cancer development, and confers greater resistance to cancer therapies. This Review discusses the mechanisms of EMT and its roles in normal and neoplastic tissues, the contribution of cell-intrinsic signals and the microenvironment to inducing EMT, and its effects on the immunobiology of carcinomas.

New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer

Emerging Biological Principles of Metastasis

Eating five servings of fruits and vegetables per day! This is what is highly recommended and heavily advertised nowadays to the general public to stay fit and healthy! Drinking green tea on a regular basis, eating chocolate from time to time, as well as savoring a couple of glasses of red wine per day have been claimed to increase life expectancy even further! Why? The answer is in fact still under scientific scrutiny, but a particular class of compounds naturally occurring in fruits and vegetables is considered to be crucial for the expression of such human health benefits: the polyphenols! What are these plant products really? What are their physicochemical properties? How do they express their biological activity? Are they really valuable for disease prevention? Can they be used to develop new pharmaceutical drugs? What recent progress has been made toward their preparation by organic synthesis? This Review gives answers from a chemical perspective, summarizes the state of the art, and highlights the most significant advances in the field of polyphenol research.

Plant Polyphenols: Chemical Properties, Biological Activities, and Synthesis

Di(indol-3-yl)methane (=3,3'-methanediyldi(1H-indole), DIM, 1) is a known weakly antitumoral compound formed by digestion of indole-3-carbinol (=1H-indol-3-ylmethanol), an ingredient of various Brassica vegetables. Out of a series of nine fluoroaryl derivatives of 1, three pentafluorophenyl derivatives 2c, 2h, and 2i were identified that exhibited a two to five times greater anti-proliferative effect and an increased apoptosis induction when compared with 1 in the following carcinoma cell lines: BxPC-3 pancreas, LNCaP prostate, C4-2B prostate, PC3 prostate and the triple-negative MDA-MB-231 breast carcinoma. Compound 2h was particularly efficacious against androgen-refractory C4-2B prostate cancer cells (IC50 =6.4 μm) and 2i against androgen-responsive LNCaP cells (IC50 =6.2 μm). In addition, 2c and 2h exhibited distinct activity in three cancer cell lines resistant to 1.

Pentafluorophenyl Substitution of Natural Di(indol-3-yl)methane Strongly Enhances Growth Inhibition and Apoptosis Induction in Various Cancer Cell Lines.

The field of cancer research has received invaluable gifts over the last few decades through novel innovations in molecular understanding and drug development. One area that is currently receiving much attention is that of microRNAs (miRNAs). The miRNAs are small, non-coding molecules that inhibit gene expression post-transcriptionally, and emerging evidence suggests that miRNAs are involved in cell growth, differentiation, and apoptosis. These developments could serve as the catalyst for further research focusing on finding a possible molecular link between miRNAs and cancer. This revolutionary research in the field of cancer has shown great promise in understanding the regulatory role of miRNAs in the development and progression of cancer, emphasizing its biochemical and pathological implications, and in particular, its significant role in cancer invasion and metastasis. For example, it has now been widely accepted that certain miRNAs are oncogenic while others act as tumor suppressors. Additionally, studies have shown that miRNAs can be used to alter sensitivity of drug-resistant tumor cells in order to improve the effects of conventional therapeutics. Furthermore, natural agents have been shown to alter miRNA expression, leading to possible inhibition of cancer cell growth and induction of apoptosis, which may contribute to the inhibition of tumor cell migration, invasion, and metastases. Therefore, selective up- and down-regulation of miRNAs holds a great promise for cancer therapy especially for those patients with invasive and metastatic disease. In this chapter, we will summarize the state of our knowledge regarding the role of miRNAs in cancer invasion and metastasis, and will also provide some information on how miRNAs could be regulated for therapeutic interventions.

MicroRNAs in cancer invasion and metastasis

Over the years, remarkable progress has been made in regards to our understanding of breast cancer biology and consequently the development of novel treatments. One idea that has proven to be immensely valuable is the use of microRNAs (miRNAs) in cancer diagnosis, prognosis, and even for treatment. The miRNAs are short RNA molecules that are able to post-transcriptionally regulate the expression of genes at multiple levels. Past and current research has continued to classify miRNAs as either highly or rarely expressed in cancer cells in relation to their normal non-cancerous counterparts. This classification is also used to organize the various miRNAs as either tumor suppressing or oncogenic. For example, aberrant expression of certain miRNAs is widely accepted to signify different stages of cancer. This chapter summarizes our current understanding of the role of miRNAs in cancer, while enlightening the readers with the role of specific miRNAs in breast cancer development and progression, and their exploitation for designing innovative therapeutic strategies.

MicroRNAs in Breast Cancer Research: Progress and Promise

Gliomas represent more than a quarter of central nervous system tumors and the vast majority of all malignant brain tumors. Patients diagnosed with a glioma generally have poor prognosis; survival is especially dismal for those harboring high-grade gliomas. With little information on the causes, and limited treatment options, there is an urgent need to better understand the underlying pathophysiology of gliomas as well as validate novel therapeutic avenues. Research in the last few years has focused on microRNAs (miRNAs) as prognostic markers as well as possible therapeutic targets in all cancers, including malignant gliomas. A number of reports have validated use of miRNAs in both in vitro and in vivo experimental models as well as clinical studies. Here, we provide an up-to-date account of the role of several key miRNAs in prognosis and/or therapy of gliomas. In particular, we discuss oncogenic miRNAs such as miRNAs-21, -182, -10b, -106b, -20a and -183 as well as tumor suppressor miRNAs such as miR-34a, -25, -32, -107, -124 and -218 for their reported roles in gliomas. The available literature on miRNAs in gliomas is encouraging and additional translational and clinical studies should be undertaken for realizing the true potential of these small regulatory RNAs.

The Therapeutic Role of MicroRNAs in Human Gliomas

Breast cancer is the most common malignant disease of women in the world and a leading cause of women’s deaths. Many risk factors such as genetics, hormones, aging, and environment have been associated with breast cancer. Interestingly, a large number of epidemiological and clinical studies suggest that obesity and diabetes, especially type-2 diabetes, are associated with higher risk of breast cancer. Similarly, these chronic diseases, such as obesity, diabetes, and cancer, are also a major public health concern in the world. Fifty percent of the United States’ population is overweight, thirty percent is obese, and ten percent has diabetes mellitus. Therefore, obesity and diabetes mellitus have been considered as potential risk factors for many cancers but this chapter is focused only on breast cancer. Although the mechanisms responsible for the development of these chronic diseases leading to the development of breast cancer are not fully understood, the biological importance of the activation of insulin, insulin like growth factor-1 (IGF-1) and its receptor (IGF-1R) signaling pathways in insulin-resistance mechanism and subsequent induction of compensatory hyperinsulinemia has been proposed. Therefore, targeting insulin/IGF-1 signaling with anti-diabetic drugs for lowering blood insulin levels and reversal of insulin-resistance could be a useful strategy for the prevention and/or treatment of breast cancer. Increased numbers of clinical studies have demonstrated that the administration of commonly used anti-diabetic drugs such as metformin decreases the risk of cancers, suggesting that these agents might be useful anti-tumor agents for the treatment of breast cancer. In this chapter, we will discuss the potential roles of anti-diabetic drug metformin as anti-tumor agents in the context of breast cancer, and will further discuss the potential roles of microRNAs (miRNAs) in the pathogenesis of obesity, diabetes, and breast cancer.

Aamir Ahmad

Papers

Pentafluorophenyl Substitution of Natural Di(indol-3-yl)methane Strongly Enhances Growth Inhibition and Apoptosis Induction in Various Cancer Cell Lines.

MicroRNAs in cancer invasion and metastasis

MicroRNAs in Breast Cancer Research: Progress and Promise

The Therapeutic Role of MicroRNAs in Human Gliomas

The Biology of the Deadly Love Connection Between Obesity, Diabetes, and Breast Cancer