title: From nature to bedside: pro-survival and cell death mechanisms as therapeutic targets in cancer treatment.
abstract: Cell death is an important physiological regulator during development, tissue homeostasis and stress response but it is also a protective tumor suppressive mechanism. Tumor cells almost universally acquire the ability to evade cell death pathways that in normal cells act as a protective mechanism to remove damaged cells. As a result, a population of death-resistant cells with accumulating genetic and epigenetic abnormalities contributes to malignant transformation. Any alteration of the homeostatic balance between survival and death is therefore a critical factor in carcinogenesis. Several forms of cell death exist and cross talk among them is emerging; however, we still miss many molecular details. It becomes essential to revisit the role of each type of cell death to understand interconnections existing between different cell death pathways as well as the network of their mediators to eventually develop new effective strategies to kill cancer cells. More specifically, new therapies based on compounds selectively triggering apoptosis, necrosis or autophagy recently became both appealing and challenging. Despite the rather clear classification of the different cell death modalities according to morphological criteria and the attempt to describe them with distinct signaling pathways, the reality reveals a complex interplay between apoptosis, regulated necrosis and autophagy involving a heterogeneous mix of molecular mediators. Nature, presenting an almost endless plenitude of bioactive scaffolds, can efficiently contribute compounds that allow deciphering the intricate pathways of cell death pathways and thus eventually contribute to selectively target cancer-type specific pathways in an attempt to personalize cancer patient treatment depending on cancer death pathway specificities. The aim of this review is to provide first an overview of molecular cell death specificities and to highlight how compounds of natural origins, with or without hemisynthetic modifications, target unique thanatotic molecular constellations.
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cerella
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Teiten
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
authors.forename: Flavia
authors.initials: F
authors.lastname: Radogna
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
authors.forename: Mario
authors.initials: M
authors.lastname: Dicato
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: marcdiederich@snu.ac.kr.
authors.forename: Marc
authors.initials: M
authors.lastname: Diederich
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D055808:Drug Discovery; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D017382:Reactive Oxygen Species; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species
keywords: Apoptosis; Autophagy; Necrosis; Reactive oxygen species