Sustained proliferation in cancer: Mechanisms and novel therapeutic targets

Abstract

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). This data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression.

Upregulated GAPLINC predicts a poor prognosis in bladder cancer patients and promotes tumor proliferation and invasion

“…The dysregulation of cell proliferation is one of the causative factors of bladder cancer (23,24). In the present study, the One Solution Cell Proliferation assay and colony formation assay demonstrated that GAPLINC knockdown significantly inhibited the proliferation of UM-UC-3 and T24 cells.…”

Regulation of MicroRNAs by Natural Products and Bioactive Compounds Obtained From Common Medicinal Plants: Novel Strategy in Cancer Therapy

“…[5][6][7][8] [13][14][15][16][17][18] The miRNAs regulated by a selection of important anticancer natural products and compounds that obtained from main known medicinal plants are presented in Table 1. As summarized in Table 1, recent studies and clinical trials which are aimed to find novel targets for the treatment of multiple types of cancers, have emphasized the importance of the consumption of natural agents-rich diet, including curcumin, berberine, alkaloids, mitomycin C, resveratrol, camptothecin, topotecan, trabectedin, matrine, honokiol, isoflovones, indole-3-carbinol, sulforaphane, water soluble vitamins, diallyl disulfide, 3,3'-diindolylmethane, epigallocatechin-3-gallate and hesperidin, etc., additionally syntheses of natural products by the liposome or nanoparticle formulations assays.…”

“…As summarized in Table 1, recent studies and clinical trials which are aimed to find novel targets for the treatment of multiple types of cancers, have emphasized the importance of the consumption of natural agents-rich diet, including curcumin, berberine, alkaloids, mitomycin C, resveratrol, camptothecin, topotecan, trabectedin, matrine, honokiol, isoflovones, indole-3-carbinol, sulforaphane, water soluble vitamins, diallyl disulfide, 3,3'-diindolylmethane, epigallocatechin-3-gallate and hesperidin, etc., additionally syntheses of natural products by the liposome or nanoparticle formulations assays. 5,7,[16][17][18] The bioactive compounds and natural products have significant influences on the epigenetic changes in the cancer cells. For instance, they regulate the expression levels of miRNAs by effecting the several proteins that are involved in the stages of tumorogenesis both cancer initiation and development.…”

“…For instance, they regulate the expression levels of miRNAs by effecting the several proteins that are involved in the stages of tumorogenesis both cancer initiation and development. 17,18 Apart from, they effect cell signaling and apoptotic pathways such as PI3K-AktmTOR, AR, Akt and ERK signaling, Wnt signaling, p53, Erb and MAPK signaling, Src/Ras/ERK and TGF-β signaling. From this point of view, intake of these natural agents by dietary regimes appears worthwhile for effective cancer therapy as a nutri-epigenetic approach, since approximately 30-35% cancer, a substantial proportion, can be prevented by dietary choices.…”

Curcumin Effect on the Expressional Profile of OCT4, Nanog and Nucleostemin Genes in AGS (Adenocarcinoma) Cancer Cell Line

“…Curcuma longa is a herbaceous plant that the rhizome is widely used to flavor and color in foods [1]. It is a dietary source of curcuminoid compounds included curcumin (75 -95%), dimethoxycurcumin and bisdimethoxy-curcumin.…”