p21 in Cancer Research

Abstract

p21 functions as a cell cycle inhibitor and anti-proliferative effector in normal cells, and is dysregulated in some cancers. Earlier observations on p21 knockout models emphasized the role of this protein in cell cycle arrest under the p53 transcription factor activity. Although tumor-suppressor function of p21 is the most studied aspect of this protein in cancer, the role of p21 in phenotypic plasticity and its oncogenic/anti-apoptotic function, depending on p21 subcellular localization and p53 status, have been under scrutiny recently. Basic science and translational studies use precision gene editing to manipulate p21 itself, and proteins that interact with it; these studies have led to regulatory/functional/drug sensitivity discoveries as well as therapeutic approaches in cancer field. In this review, we will focus on targeting p21 in cancer research and its potential in providing novel therapies.

Isoliquiritigenin inhibits the proliferation, migration and metastasis of Hep3B cells via suppressing cyclin D1 and PI3K/AKT pathway

“…In tumor cells, overexpression of cyclin D1 and down-regulation or dysfunction of its negative regulatory proteins P21 and P27 are very common, these changes are closely related to the abnormal proliferation of tumors. Molecular mechanisms leading to this abnormal expression include overexpression of oncogenes such as c-Myc [29], FBXO22 [30], miR-95-3p [31], deletion or mutation of tumor suppressor gene such as P53 [32], and abnormal activation of the cancer-promoting signaling pathways such as PI3K/AKT pathway [32][33][34]. In the present study, we noted an abnormal overexpression of cyclin D1 in Hep3B cells both at the mRNA and protein levels.…”

Understanding Failure and Improving Treatment Using HDAC Inhibitors for Prostate Cancer

“…Following HDAC inhibition, p21 levels have been upregulated in various cancers [126,128]. A plethora of studies highlight the role of p21 in cell cycle arrest in response to HDAC inhibition [102,103].…”

Glucosinolate-Degradation Products as Co-Adjuvant Therapy on Prostate Cancer in Vitro

“…Although mechanisms by which they produce these anti-cancer effects are not fully known, their cytotoxic action is usually associated with cell cycle arrest and activation of apoptosis [8,18], as it has been shown in the present study. PC-3 cells treated with AITC and IB increased the expression of p21 and the Bax/Bcl-2 expression ratio, which in turn promotes G1 cell cycle phase arrest [19] and induces the release of cytochrome c causing mitochondrial dysfunction [20]. Collectively, these findings suggest that checkpoints for cell cycle arrest and programmed cell death are regulated by ITCs in PC cells.…”