Predicting PARP inhibitor sensitivity and resistance

A healthy diet rich in fruits and vegetables is an important part of a healthy lifestyle. Whereas epidemiological data sometimes fail to provide proof of this concept, molecular evidence is accumulating that clearly shows both preventive as well as therapeutic effects of compounds from natural origins. in the paper of Guido Kroemer's group about pro-autophagic polyphenols and their inhibitory effect on acetylation of cytoplasmic proteins, much emphasis is given to the relevance of this molecular mechanism in various diseases, including cardiovascular (French paradox) and neurodegenerative diseases as well as cancer. in fact, more than 75% of all anticancer drugs used in the clinics are of natural origins or at least inspired from nature. Based on this observation, many international research groups aim at discovering molecular mechanisms triggered or inhibited by compounds from nature. These compounds are sometimes controversially considered an excellent source for future preventive interventions as well as natural anticancer drugs able to target the main hallmarks of cancer or their enabling characteristics. Accordingly, molecular hallmarks that are efficiently inhibited by various natural compounds from the daily diet could be documented over the last decade. in our recent review, 1 various compounds from the " garden " are matched with their target signaling pathways: diallylpolysulfides from garlic induce cell cycle arrest and lead to apoptotic cell death; epigallocatechin 3-gallate (eGCG), curcumin and capsaicin were reported to inhibit epider-mal growth factor receptor (eGFR) cell signal-ing pathways; β-lapachone from the bark of Tabebuia avellanedae induces a reduction of the telomerase RNA level; flavonoids like lute-olin or genistein inhibit mechanisms linked to metastasis formation; angiogenesis is inhibited by plumbagin; methyl jasmonate inhibits cancer cell metabolism by active induction of hexokinase release; cordycepin inhibits PARP-1-involved base excision repair and finally a wealth of compounds were shown to inhibit pro-inflammatory cell signaling mechanisms including NFκB and Jak/STAT. it becomes clear that even from our diet, nature provides arrays of molecules able to interfere with all crucial steps of carcinogenesis, covering initiation, promotion and progression of the disease. Natural compounds that interfere with autophagic mechanisms are much less investigated and, accordingly, deserve particular attention, as they could lead to therapeutic applications in cancer types resistant toward apoptotic cell death. in the report by Pietrocola et al., 3 authors show that pro-autophagic polyphenols reduce the acetylation level of cytoplasmic proteins, and that a cause-effect relationship between this deacetylation and autophagy induction by red wine components exists. …