Colorectal-cancer (CRC) is the third leading cause of death due to cancer, supporting the need for identification of novel anticancer drug to improve the efficacy of current-therapy. There is growing bodies of data showing the antitumor-activity of curcumin, although it is associated with low absorption. The aim of current study was explored the therapeutic-potential of novel phytosomal curcumin as well as its application in combination with 5-Flurouracil (5-FU) in a mouse-model of colitis-associated colon-cancer. The anti-proliferative-activity of phytosomal curcumin was assessed in 2- and 3-dimensional cell-culture-models as well as in a mouse-model of colitis-associated colon-cancer. The expression-levels of CyclinD1, beclin, E-cadherin, and p-GSK3a/b were investigated by qRT-PCR and/or Western-blotting. We evaluated the anti-inflammatory of this agent by pathological-evaluation and disease-activity-index (DAI). Moreover, oxidant/antioxidant activity was examined by malondialdehyde (MDA), total-thiols (T-SH), superoxide-dismutase (SOD), and catalase (CAT) activity parameters. Our data showed that phytosomal curcumin and its combination with 5-FU inhibited cell growth and invasive behavior of CRC cells through modulation of Wnt-pathway and E-cadherin. Combination of curcumin with 5-FU dramatically reduced the tumor-number and tumor-size in both distal and middle parts of colon in colitis-associated colon cancer followed by reduction in DAI. Also, curcumin suppressed the colonic inflammation and notably recovered the increased levels of MDA, decreased thiol level and reduced activity of CAT. We demonstrated the antitumor-activity of novel form of curcumin in CRC, supporting further investigations on the therapeutic-potential of this approach in colorectal-cancer.
Cytokine members of the IL-12 family have attracted enormous attention in the last few years, with IL-35 being the one of the most attractive-suppressive cytokine. IL-35 is an important mediator of regulatory T cell function. Regulatory T cells play key roles in restoring immune homeostasis after facing challenges such as infection by specific pathogens. Moreover, a crucial role for regulatory T cell populations has been demonstrated in several physiological processes, including establishment of fetal-maternal tolerance, maintenance of self-tolerance and prevention of autoimmune diseases. However, a deleterious involvement of immune regulatory T cells has been documented in specific inhibition of immune responses against tumor cells, promotion of chronic infections and establishment of chronic inflammatory disorders. In this review, we attempt to shed light on the concept of immune-homoeostasis on the aforementioned issues, taking IL-35 as the hallmark of regulatory responses. The dilemma between immune-mediated cancer treatment and inflammation is discussed. Histopathological indications of chronic vs. acute infections are elaborated. Moreover, the evidence that IL-35 requires additional immune-regulatory cytokines, such as IL-10 and TGF-β, to induce effective and maximal anti-inflammatory effects suggest that immune-regulation requires multi-factorial analysis of many immune playmakers rather than a specific immune target.
Curcuminoids are turmeric-extracted phytochemicals with documented chemopreventive and anti-tumor activities against several types of malignancies. Curcuminoids can modulate several molecular pathways and cellular targets involved in different stages of tumor initiation, growth, and metastasis. Bisdemethoxycurcumin (BDMC) is a minor constituent (approximately 3%) of curcuminoids that has been shown to be more stable than the other two main curcuminoids, that is, curcumin and demthoxycurcumin. Recent studies have revealed that BDMC has anti-tumor effects exerted through a multimechanistic mode of action involving inhibition of cell proliferation, invasion and migration, metastasis and tumour growth, and induction of apoptotic death in cancer cells. The present review discusses the findings on the anti-tumor effects of BDMC, underlying mechanisms, and the relevance of finding for translational studies in human.
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