Low‐dose UV‐radiation sensitizes keratinocytes to TRAIL‐induced apoptosis

Qin, Jian‐Zhong; Bacon, Patricia; Panella, Jeffrey; Sitailo, Leonid A.; Denning, Mitchell F.; Nickoloff, Brian J.

doi:10.1002/jcp.20017

Cited by 36 publications

(28 citation statements)

References 44 publications

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“…30 In vitro, it has been reported to reduce the effect of ultraviolet radiation in experiments with cultured cell lines. 31,32 On the other hand, under other experimental conditions PDTC has acted as a pro-oxidant. 33,34 Given the clear distinction in the in vivo transplant experiments and conflicting in vitro reports in the literature, we chose two in vitro tests to compare the effects of amifostine and its active metabolite WR-1065 with NAC and PDTC.…”

Section: Discussionmentioning

confidence: 99%

Amifostine prior to lethal irradiation prevents allogeneic bone marrow engraftment in mice

Thompson

Asmis

Chu

et al. 2008

Bone Marrow Transplant

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Section: Discussionmentioning

confidence: 99%

Amifostine prior to lethal irradiation prevents allogeneic bone marrow engraftment in mice

Thompson

Asmis

Chu

et al. 2008

Bone Marrow Transplant

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“…The dominant-negative Fas-associating protein with death domain (FADD DN) cDNA was provided by Dr. Vishva Dixit (Genentech, Inc., South San Francisco, CA), and was subcloned into the BamHI and NotI sites of LZRS retroviral expression vector as previously described (29). A Bcl-x L retroviral construct was also used as previously described (30).…”

Section: Methodsmentioning

confidence: 99%

Proteasome Inhibitors Trigger NOXA-Mediated Apoptosis in Melanoma and Myeloma Cells

et al. 2005

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Patients with metastatic melanoma or multiple myeloma have a dismal prognosis because these aggressive malignancies resist conventional treatment. A promising new oncologic approach uses molecularly targeted therapeutics that overcomes apoptotic resistance and, at the same time, achieves tumor selectivity. The unexpected selectivity of proteasome inhibition for inducing apoptosis in cancer cells, but not in normal cells, prompted us to define the mechanism of action for this class of drugs, including Food and Drug Administration-approved bortezomib. In this report, five melanoma cell lines and a myeloma cell line are treated with three different proteasome inhibitors (MG-132, lactacystin, and bortezomib), and the mechanism underlying the apoptotic pathway is defined. Following exposure to proteasome inhibitors, effective killing of human melanoma and myeloma cells, but not of normal proliferating melanocytes, was shown to involve p53-independent induction of the BH3-only protein NOXA. Induction of NOXA at the protein level was preceded by enhanced transcription of NOXA mRNA. Engagement of mitochondrial-based apoptotic pathway involved release of cytochrome c, second mitochondria-derived activator of caspases, and apoptosis-inducing factor, accompanied by a proteolytic cascade with processing of caspases 9, 3, and 8 and poly(ADP)-ribose polymerase. Blocking NOXA induction using an antisense (but not control) oligonucleotide reduced the apoptotic response by 30% to 50%, indicating a NOXAdependent component in the overall killing of melanoma cells. These results provide a novel mechanism for overcoming the apoptotic resistance of tumor cells, and validate agents triggering NOXA induction as potential selective cancer therapeutics for life-threatening malignancies such as melanoma and multiple myeloma. (Cancer Res 2005; 65(14): 6282-93)

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“…To reduce Mcl-1 levels using UV light, melanoma cells were grown in 10-cm tissue culture plates and the lid and medium were removed followed by UV irradiation using a Panelite unit (Ultralite Enterprise, Inc., Lawrenceville, GA). This light source consists of four UVB bulbs (FS36T12/UVB-VHO) and the output wavelengths of the bulbs are 65% UVB, 34% UVA, and 1% UVC as described previously (37). The UV dose was monitored with an International Light, Inc. (Newburyport, CT) radiometer fitted with a UVB detector.…”

Section: Methodsmentioning

confidence: 99%

Enhanced Killing of Melanoma Cells by Simultaneously Targeting Mcl-1 and NOXA

et al. 2006

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By deciphering the dysregulation of apoptosis in melanoma cells, new treatment approaches exploiting aberrant control mechanisms regulating cell death can be envisioned. Among the Bcl-2 family, a BH3-only member, NOXA, functions in a specific mitochondrial-based cell death pathway when melanoma cells are exposed to a proteasome inhibitor (e.g., bortezomib). Some therapeutic agents, such as bortezomib, not only induce proapoptotic Bcl-2 family members and active conformational changes in Bak and Bax but also are associated with undesirable effects, including accumulation of antiapoptotic proteins, such as Mcl-1. To enhance the bortezomib-mediated killing of melanoma cells, the apoptotic pathway involving NOXA was further investigated, leading to identification of an important target (i.e., the labile Bcl-2 homologue Mcl-1 but not other survival proteins). To reduce Mcl-1 levels, melanoma cells were pretreated with several different agents, including Mcl-1 small interfering RNA (siRNA), UV light, or the purine nucleoside analogue fludarabine. By simultaneously triggering production of NOXA (using bortezomib) as well as reducing Mcl-1 levels (using siRNA, UV light, or fludarabine), significantly enhanced killing of melanoma cells was achieved. These results show binding interactions between distinct Bcl-2 family members, such as NOXA and Mcl-1, in melanoma cells, paving the way for novel and rational therapeutic combination strategies, which target guardians of the proapoptotic Bak-and Baxmediated pathways, against this highly aggressive and often fatal malignancy.

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Low‐dose UV‐radiation sensitizes keratinocytes to TRAIL‐induced apoptosis

Cited by 36 publications

References 44 publications

Amifostine prior to lethal irradiation prevents allogeneic bone marrow engraftment in mice

Amifostine prior to lethal irradiation prevents allogeneic bone marrow engraftment in mice

Proteasome Inhibitors Trigger NOXA-Mediated Apoptosis in Melanoma and Myeloma Cells

Enhanced Killing of Melanoma Cells by Simultaneously Targeting Mcl-1 and NOXA

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