Crosstalk between Apoptosis and Autophagy: Molecular Mechanisms and Therapeutic Strategies in Cancer

Abstract

Both apoptosis and autophagy are highly conserved processes that besides their role in the maintenance of the organismal and cellular homeostasis serve as a main target of tumor therapeutics. Although their important roles in the modulation of tumor therapeutic strategies have been widely reported, the molecular actions of both apoptosis and autophagy are counteracted by cancer protective mechanisms. While apoptosis is a tightly regulated process that is implicated in the removal of damaged or unwanted cells, autophagy is a cellular catabolic pathway that is involved in lysosomal degradation and recycling of proteins and organelles, and thereby is considered an important survival/protective mechanism for cancer cells in response to metabolic stress or chemotherapy. Although the relationship between autophagy and cell death is very complicated and has not been characterized in detail, the molecular mechanisms that control this relationship are considered to be a relevant target for the development of a therapeutic strategy for tumor treatment. In this review, we focus on the molecular mechanisms of apoptosis, autophagy, and those of the crosstalk between apoptosis and autophagy in order to provide insight into the molecular mechanisms that may be essential for the balance between cell survival and death as well as their role as targets for the development of novel therapeutic approaches.

Three Bufadienolides-Induced Human Lung Cancer CL1-5 Cell Death Mainly through Autophagy

“…Numerous studies showed that apoptosis or a reciprocal action between apoptosis and autophagy is the major process to control cell fates [8,9,12,24,25]. Interestingly, the findings of this study showed that bufadienolides KB, KA, and BC do not induce cellular apoptosis but only induced cell autophagy.…”

“…In some cases, autophagy and apoptosis modulate each other to control cell fates [24,25,29]. It has also been known that autophagy acts as a pro-death pathway and is called autophagic cell death which is different from apoptotic cell death [30,31].…”

Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia

“…Apart from their physiological role in the maintenance of cellular homeostasis, apoptosis and autophagy serve as important targets of tumor therapeutics. [23][24][25][26][27][28][29] Whereas apoptosis is implicated in the removal of damaged or unwanted cells, autophagy is a cellular catabolic pathway that is involved in lysosomal degradation and recycling of proteins and organelles, and is therefore considered as an important survival mechanism for both normal cells and cancer cells in response to metabolic stress or chemotherapy. In hematologic malignancies, autophagy can either act as a chemoresistance ©2015 Ferrata Storti Foundation.…”

Luteolin Promotes Cell Apoptosis by Inducing Autophagy in Hepatocellular Carcinoma

“…Basal levels of autophagy are required for cellular homeostasis. Autophagy is upregulated under various cellular stresses, such as infection, starvation, organelle damage, and protein aggregation [13, 14]. Autophagy has complicated functions in different stages of cancer [15].…”

“…Autophagy is a catabolic process by which cytoplasmic components, such as damaged organelles, aged proteins, and damaged proteins, are sequestered by a double-membrane autophagosome, and delivered to the lysosome for degradation [13]. Basal levels of autophagy are required for cellular homeostasis.…”