Senescence and Cell Death Pathways and Their Role in Cancer Therapeutic Outcome

Abstract

Anticancer drug-induced tumor suppression may involve mechanisms of protection against neoplastic transformation that are normally latent in mammalian cells and consist in a genetic program implemented during anti-tumoral defense. This defense program results in the self elimination of cells harboring potentially dangerous mutations by triggering cell death through apoptosis and/or autophagy or in the execution of a program that leads to a permanent growth arrest known as senescence. These responses are considered crucial tumor suppressive mechanisms and their study appears to be essential to develop therapeutical procedures based on the enhancement of the different responses. This review summarizes fundamental knowledge on the underlying mechanisms able to limit excessive or aberrant cellular proliferation and on the prognostic value of both apoptosis and senescence detection. In addition, interesting evidence showing that different drugs induce senescence or cell death depending on the genetic features of the tumor cells as well as on the integrity of the relative pathways is reported.

Liver Yin deficiency tonifying herbal extract induces apoptosis and cell senescence in Bel-7402 human hepatocarcinoma cells

“…Apoptosis is an evolutionarily conserved cell suicide process elicited by physiological, pharmacological and pathological conditions. The initiation and execution of apoptosis depends on the activation of the extrinsic and/or intrinsic death pathways (28,29). Extrinsic or death receptor pathways are associated with death receptors, such as FAS, the TRAIL receptor (TRAIL-R) and TNF receptor (TNF-R).…”

“…Cell senescence is usually characterized by a large and flattened morphology, an increase in intracellular granules and elevated SA-β-gal activity (30). Similar to apoptosis, cell senescence plays a crucial role in suppressing tumorigenesis and may contribute to the outcome of cancer therapy (29)(30)(31)(32). It has been shown that chemotherapeutic agents, such as cisplatin, doxorubicin, SN-38 and camptothecin, inhibit the growth of tumors via cell senescence (32)(33)(34)(35).…”

Expression of Beclin1 in osteosarcoma and the effects of down-regulation of autophagy on the chemotherapeutic sensitivity

“…Autophagy, also described as type Ⅱ programmed cell death, is constitutive in all types of cells containing a lysosomal compartment. This housekeeping function is involved in cytoplasmic homeostasis because it controls the turnover of long-lived proteins and probably also the remodeling of the cytoplasm [13][14][15] . Beclin1 is a 60 kDa coiled-coil protein, and forms a protein complex with a phosphatidyl insositol-3-kinase (PI3K) within the autophagosome [16] .…”

Aqueous Extract of Curcuma aromatica Induces Apoptosis and G2/M Arrest in Human Colon Carcinoma LS-174-T Cells Independent of p53

“…[10][11][12] So, next, the effects of AECA on cell apoptosis and cell cycle distribution in LS-174-T cells were determined by flow cytometry analysis. As shown in Figure 3, apoptosis was detected in LS-174-T cell following 72 hours of exposure to various doses of AECA in a dose-dependent manner and compared with the controls ( p < 0.05).…”