Small molecule compounds that induce cellular senescence

Abstract

SummaryTo date, dozens of stress-induced cellular senescence phenotypes have been reported. These cellular senescence states may differ substantially from each other, as well as from replicative senescence through the presence of specific senescence features. Here, we attempted to catalog virtually all of the cellular senescencelike states that can be induced by low molecular weight compounds. We summarized biological markers, molecular pathways involved in senescence establishment, and specific traits of cellular senescence states induced by more than fifty small molecule compounds.

Hydroxyurea‐induced senescent peripheral blood mesenchymal stromal cells inhibit bystander cell proliferation of JAK2V617F‐positive human erythroleukemia cells

“…Namely, HU provokes a deoxyribonucleotides, double‐strand DNA breaks near to replication forks, and inhibits both nuclear and mitochondrial DNA replication, thus causing cellular and mitochondrial dysfunctions . Moreover, HU is a DNA replication stress inducer and can induce senescence‐like phenotype in both transformed and primary cells .…”

“…Chemotherapeutic drugs can induce the persistent presence of senescent cells in normal noncancerous tissues . In vitro studies have demonstrated that different transformed cell lines and primary cells, such as fibroblasts and mesenchymal stromal cells (MSC) can display a senescence‐like phenotype . Although MSC circulate at a very low level in healthy individuals, peripheral blood MSC (PBMSC) are increased in pathological conditions .…”

Using the drug-protein interactome to identify anti-ageing compounds for humans

“…Additionally, using literature mining, we identified studies showing the association with longevity of cAMP analogues [28], selenium [29,30] and tanespimycin [31,32]. In contrast, we also found evidence for the DNA-mediated, pro-ageing (anti-longevity) effects of doxorubicin [33], cisplatin [34] and hydrogen peroxide [35]. We performed an interaction-based similarity analysis and found that the genotoxic compounds cluster separately from the other drugs, suggesting that they have a similar mechanism of action (S2 text).…”

Autophagy regulates the localization and degradation of p16INK4a

“…However, cytoplasmic p16 has also been reported as correlating with the absence of metastasis in other cancer types, such as melanoma [7]. Commonly used chemotherapeutic drugs such as etoposide and doxorubicin can increase p16 protein levels and induce senescence [8], but whether and to what extent these agents affect p16 localization has not been fully explored. Interestingly, p16 does not have a known nuclear localization signal (NLS) or a nuclear export signal (NES) [9], suggesting that an indirect mechanism of intracellular transport is responsible for shuttling p16 between different cellular compartments [10].…”