Arsenite induced poly(ADP-ribosyl)ation of tumor suppressor P53 in human skin keratinocytes as a possible mechanism for carcinogenesis associated with arsenic exposure

Komissarova, Elena V.; Rossman, Toby G.

doi:10.1016/j.taap.2009.12.014

Cited by 42 publications

(26 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Following the 2-week removal of MMA III , these levels were similar to that of control. These results were similar to those demonstrated by Komissarova and Rossman (2010) in which 14-day exposure to 0.1 μM arsenite in HaCaT caused a decrease in total protein poly(ADP-ribosyl)ation and an increase in total PARP-1 protein levels. It has been suggested that PARP-1 gene transcription is self-regulated via the auto-poly(ADP-ribosyl)ation of PARP-1 protein.…”

Section: Discussionsupporting

confidence: 91%

Interdependent genotoxic mechanisms of monomethylarsonous acid: Role of ROS-induced DNA damage and poly(ADP-ribose) polymerase-1 inhibition in the malignant transformation of urothelial cells

Wnek

Kuhlman

Camarillo

et al. 2011

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

Exposure of human bladder urothelial cells (UROtsa) to 50 nM of the arsenic metabolite, monomethylarsonous acid (MMAIII), for 12 weeks results in irreversible malignant transformation. The ability of continuous, low-level MMAIII exposure to cause an increase in genotoxic potential by inhibiting repair processes necessary to maintain genomic stability is unknown. Following genomic insult within cellular systems poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger protein, is rapidly activated and recruited to sites of DNA strand breaks. When UROtsa cells are continuously exposed to 50 nM MMAIII, PARP-1 activity does not increase despite the increase in MMAIII-induced DNA single-strand breaks through 12 weeks of exposure. When UROtsa cells are removed from continuous MMAIII exposure (2 weeks), PARP-1 activity increases coinciding with a subsequent decrease in DNA damage levels. Paradoxically, PARP-1 mRNA expression and protein levels are elevated in the presence of continuous MMAIII indicating a possible mechanism to compensate for the inhibition of PARP-1 activity in the presence of MMAIII. The zinc finger domains of PARP-1 contain vicinal sulfhydryl groups which may act as a potential site for MMAIII to bind, displace zinc ion, and render PARP-1 inactive. Mass spectrometry analysis demonstrates the ability of MMAIII to bind a synthetic peptide representing the zinc-finger domain of PARP-1, and displace zinc from the peptide in a dose-dependent manner. In the presence of continuous MMAIII exposure, continuous 4-week zinc supplementation restored PARP-1 activity levels and reduced the genotoxicity associated with MMAIII. Zinc supplementation did not produce an overall increase in PARP-1 protein levels, decrease the levels of MMAIII-induced reactive oxygen species, or alter Cu-Zn superoxide dismutase levels. Overall, these results present two potential interdependent mechanisms in which MMAIII may increase the susceptibility of UROtsa cells to genotoxic insult and/or malignant transformation: elevated levels of MMAIII-induced DNA damage through the production of reactive oxygen species, and the direct MMAIII-induced inhibition of PARP-1.

show abstract

Section: Discussionsupporting

confidence: 91%

Interdependent genotoxic mechanisms of monomethylarsonous acid: Role of ROS-induced DNA damage and poly(ADP-ribose) polymerase-1 inhibition in the malignant transformation of urothelial cells

Wnek

Kuhlman

Camarillo

et al. 2011

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

show abstract

“…In addition the 2 flavonoids were tested also on HaCaT cells, a spountanously immortalized noncancerogenic keratinocytes cell line, used as control nontumoral cells that they may be considered a model of the initial transformation of SCC (20).…”

Section: Discussionmentioning

confidence: 99%

Myricetin and Naringenin Inhibit Human Squamous Cell Carcinoma Proliferation and Migration In Vitro

Maggioni

Nicolini

Rigolio

et al. 2014

Nutrition and Cancer

View full text Add to dashboard Cite

In this study the potential anticancer effect of 2 flavonoids, myiricetin (MYR) and naringenin (NAR) has been evaluated on an oral squamous cell carcinoma (OSCC) cell line, SCC-25, and HaCaT cells. Both the flavonoids inhibited SCC-25 cell growth, although NAR selectively affected cancer cells without impairing HaCaT cell growth. The cell proliferation inhibition by MYR and NAR was not related to apoptosis induction, but on cell cycle impairment, because a G0/G1 and a G2/M blockage was highlighted following 24 h of treatment in SCC-25 and HaCaT cells, respectively. Western blot analysis showed that MYR induced a decrease of Cyclin D1 in SCC-25 and of Cyclin B1 in HaCaT cells, while NAR negatively modulated Cyclin D1 expression in SCC-25 cells. Wound-healing and cell invasion assays demonstrated that both the flavonoids were able to reduce motility on both SCC-25 and HaCaT cells. In conclusion the results of the present study show the anticancer potential of NAR and MYR on OSCC because they exert cytostatic effect by the impairment of cell cycle progression. Moreover both the flavonoids inhibit cell migration, thus highlighting their potential effect as antimetastatic agents. Therefore, MYR and NAR appear as promising candidate as oral cancer chemopreventive agents.

show abstract

“…Additional studies have shown that the p53-dependent increase in p21 expression observed in normal cells following DNA damage is inhibited in cells exposed to arsenic, leading to cell cycle progression despite heavy DNA damage and genomic instability [58-61]. Similarly, arsenic-induced disruption of PARP1 activity contributes to genomic instability by allowing the survival of cells with significant DNA lesions [51,62].…”

Section: Introductionmentioning

confidence: 99%

Molecular features in arsenic-induced lung tumors

Hubaux¹,

Becker‐Santos²,

Enfield³

et al. 2013

Mol Cancer

115

View full text Add to dashboard Cite

Arsenic is a well-known human carcinogen, which potentially affects ~160 million people worldwide via exposure to unsafe levels in drinking water. Lungs are one of the main target organs for arsenic-related carcinogenesis. These tumors exhibit particular features, such as squamous cell-type specificity and high incidence among never smokers. Arsenic-induced malignant transformation is mainly related to the biotransformation process intended for the metabolic clearing of the carcinogen, which results in specific genetic and epigenetic alterations that ultimately affect key pathways in lung carcinogenesis. Based on this, lung tumors induced by arsenic exposure could be considered an additional subtype of lung cancer, especially in the case of never-smokers, where arsenic is a known etiological agent. In this article, we review the current knowledge on the various mechanisms of arsenic carcinogenicity and the specific roles of this metalloid in signaling pathways leading to lung cancer.

show abstract

Arsenite induced poly(ADP-ribosyl)ation of tumor suppressor P53 in human skin keratinocytes as a possible mechanism for carcinogenesis associated with arsenic exposure

Cited by 42 publications

References 51 publications

Interdependent genotoxic mechanisms of monomethylarsonous acid: Role of ROS-induced DNA damage and poly(ADP-ribose) polymerase-1 inhibition in the malignant transformation of urothelial cells

Interdependent genotoxic mechanisms of monomethylarsonous acid: Role of ROS-induced DNA damage and poly(ADP-ribose) polymerase-1 inhibition in the malignant transformation of urothelial cells

Myricetin and Naringenin Inhibit Human Squamous Cell Carcinoma Proliferation and Migration In Vitro

Molecular features in arsenic-induced lung tumors

Contact Info

Product

Resources

About