Autophagy Takes Center Stage as a Possible Cancer Hallmark

Abstract

Cancer remains one of the leading causes of death worldwide, despite significant advances in cancer research and improvements in anticancer therapies. One of the major obstacles to curing cancer is the difficulty of achieving the complete annihilation of resistant cancer cells. The resistance of cancer cells may not only be due to intrinsic factors or factors acquired during the evolution of the tumor but may also be caused by chemotherapeutic treatment failure. Conversely, autophagy is a conserved cellular process in which intracellular components, such as damaged organelles, aggregated or misfolded proteins and macromolecules, are degraded or recycled to maintain cellular homeostasis. Importantly, autophagy is an essential mechanism that plays a key role in tumor initiation and progression. Depending on the cellular context and microenvironmental conditions, autophagy acts as a double-edged sword, playing a role in inducing apoptosis or promoting cell survival. In this review, we propose several scenarios in which autophagy could contribute to cell survival or cell death. Moreover, a special focus on novel promising targets and therapeutic strategies based on autophagic resistant cells is presented.

The Etiology and Pathophysiology Genesis of Benign Prostatic Hyperplasia and Prostate Cancer: A New Perspective

“…Central to testosterone-vascular-inflamm-ageing triad is the early induction of amyloidosis and autophagy, which play a role in early tumor suppression in terms of the cell regulation pathways, and in their dysregulation in late stages where they act as tumor promoters [86][87][88][89][90]; this correlates to "ageing autophagy" [91][92][93][94]. Short term estrogen reduction using aromatase inhibitor in the adult Wistar male rat alters the prostatic function by reducing nitric oxide availability, inducing amyloid deposition and limiting the differentiation of basal cells through a lobe specific p63-overexpression [95].…”

“…This is the threshold point at the start of "prostate reprogramming" and the "loss" of cell function, homeostasis and regulation pathways [192][193][194][195][196][197]. It marks the beginning of a prostate stagnation tumorigenesis inflammatory microenvironment with heterogeneous events [17] including inflammation [57, [140][141][142]198], genetic aberrations [199][200][201][202][203][204][205], epigenetic dysregulation [206][207][208][209][210], autophagy dysregulation [86,87,89,90,[211][212][213][214][215][216] and lysosomal dysfunction [217][218][219][220].…”

“…These should also be complemented consistently with a healthy diet and lifestyle [224][225][226][227]. The future paradigm shift involves an emphasis on prevention as early maintenance of healthy vascular function is necessary to preserve cell function, homeostasis and regulation [166,193], thus prolonging the function of the prostate gland, and delaying/avoiding late stage amyloidosis and autophagy dysregulation [86][87][88][89][90]. Other, potential strategies for ameliorating these biological processes of endothelial dysfunction, oxidative stress and inflammation [221][222][223] could be developed.…”

New Amides and Phosphoramidates Containing Selenium: Studies on Their Cytotoxicity and Antioxidant Activities in Breast Cancer

“…After treatment with I.1f, I.2f and II.2d at various time points (24-72 h for I.1f and 8-48 h for I.2f and II2d), the results suggested that these compounds arrested cell cycle in a time-dependent fashion (Figure 7). Apoptosis and autophagy are considered as two recognized pathways for anticancer agents due to their effects on cell survival [37,38]. In the next step, in order to investigate whether the cell death pathway is related to apoptosis or autophagy, we explored the effect of pre-treated cells with either an autophagy inhibitor (wortmannin) or a pan-caspase inhibitor (Z-VAD-FMK).…”

Inhibition Effect of Chloroquine and Integrin-Linked Kinase Knockdown on Translation in Melanoma Cells

“…In cancer biology, autophagy plays a dual role in cell survival and cell death. On the one hand, autophagy inhibits the growth and development of cancer, and on the other, it allows it to survive during chemotherapy [1][2][3][4][5][6]. Cancer cells are more autophagy-dependent than normal cells, thus, targeting autophagy is a therapeutic strategy for cancer therapy [4][5][6].…”