Pio suppresses the proliferation of MCF7 cells, at least partly by a PPAR-γ-independent mechanism involving the induction of p21 which in turn requires sustained activation of MAPK. These findings implicate the utility of Pio in the treatment of PPAR positive or negative human cancers and the development of a new class of compounds to enhance the effectiveness of Pio.
Stromal heterogeneity of tumor microenvironment (TME) plays a crucial role in malignancy and therapeutic resistance. Cancer-associated fibroblasts (CAFs) are one of the major players in tumor stroma. The heterogeneous sources of origin and subsequent impacts of crosstalk with breast cancer cells flaunt serious challenges before current therapies to cure triple-negative breast cancer (TNBC) and other cancers. The positive and reciprocal feedback of CAFs to induce cancer cells dictates their mutual synergy in establishing malignancy. Their substantial role in creating a tumor-promoting niche has reduced the efficacy of several anti-cancer treatments, including radiation, chemotherapy, immunotherapy, and endocrine therapy. Over the years, there has been an emphasis on understanding CAF-induced therapeutic resistance in order to enhance cancer therapy results. CAFs, in the majority of cases, employ crosstalk, stromal management, and other strategies to generate resilience in surrounding tumor cells. This emphasizes the significance of developing novel strategies that target particular tumor-promoting CAF subpopulations, which will improve treatment sensitivity and impede tumor growth. In this review, we discuss the current understanding of the origin and heterogeneity of CAFs, their role in tumor progression, and altering the tumor response to therapeutic agents in breast cancer. In addition, we also discuss the potential and possible approaches for CAF-mediated therapies.
Parthenolide (PTL), the secondary metabolite of feverfew plant (Tanaceum parthenium), has been used in various medical purposes globally. Inflammation represents a physiological response to injury and helps to restore tissue homeostasis. Inflammation and cancer both are associated with genotoxicity, invasion, metastasis, and abnormal tissue repair mechanisms. PTL inhibit major cellular inflammatory and proliferation pathways like NFκB, STAT3, and MAPK along with the activity and expression of several inflammatory mediators including COX. NFκB pathway plays a key role in controlling cell cycle progression and apoptosis together with metastasis and cancer of various types. Elevated NFκB, Wnt/β-catenin pathways are crucial factors of tumorogenesis. PTL inhibits NFκB and Wnt/β-catenin pathways, and thereby promotes apoptosis and suppresses cell proliferation. Experimental data showed that PTL protects normal cells from apoptosis; whereas in cancer cells it induces apoptotic cell death. Hence, parthenolide could be useful in controlling inflammatory diseases alone or together with tumorogenesis due to its evident anticancer potency and anti-inflammatory nature.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.