Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro
Authors
Popović, JelenaLazić, Andrijana
Paunesku, Tatjana
Ma, Qing
Chen, Si
Lai, Barry
Stevanović, Milena
Woloschak, Gayle E.
Article (Published version)
Metadata
Show full item recordAbstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of platinum-based chemotherapy and decreases the quality of life of cancer patients. We compared neuroprotective properties of several agents using an in vitro model of terminally differentiated human cells NT2-N derived from cell line NT2/D1. Sodium azide and an active metabolite of amifostine (WR1065) increase cell viability in simultaneous treatment with cisplatin. In addition, WR1065 protects the non-dividing neurons by decreasing cisplatin caused oxidative stress and apoptosis. Accumulation of Pt in cisplatin-treated cells was heterogeneous, but the frequency and concentration of Pt in cells were lowered in the presence of WR1065 as shown by X-ray fluorescence microscopy (XFM). Transition metals accumulation accompanied Pt increase in cells; this effect was equally diminished in the presence of WR1065. To analyze possible chemical modulation of Pt-DNA bonds, we examined the platinum L-III near edge spectrum by X-ra...y absorption spectroscopy. The spectrum found in cisplatin-DNA samples is altered differently by the addition of either WR1065 or sodium azide. Importantly, a similar change in Pt edge spectra was noted in cells treated with cisplatin and WR1065. Therefore, amifostine should be reconsidered as a candidate for treatments that reduce or prevent CIPN.
Keywords:
XFM / Neuroprotection / Cisplatin / CIPN / AmifostineSource:
Cellular and Molecular Neurobiology, 2019, 39, 5, 619-636Publisher:
- Springer/Plenum Publishers, New York
Funding / projects:
- Studying signal transduction pathways and epigenetic mechanisms that control human SOX genes expression: further insight into their roles in cell fate determination and differentiation (RS-MESTD-Basic Research (BR or ON)-173051)
- UICC Yamagiwa-Yoshida Memorial International Cancer Study Grant [YY2/2015/381414]
- U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]
- NIH ARRA Grant [SP0007167]
- Northwestern University
- E. I. DuPont de Nemours Co.
- Dow Chemical Company
- NCI CCSG [P30 CA060553]
- NIH [1S10OD010398-01]
DOI: 10.1007/s10571-019-00667-7
ISSN: 0272-4340
PubMed: 30874981
WoS: 000469033100005
Scopus: 2-s2.0-85062973382
Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Popović, Jelena AU - Lazić, Andrijana AU - Paunesku, Tatjana AU - Ma, Qing AU - Chen, Si AU - Lai, Barry AU - Stevanović, Milena AU - Woloschak, Gayle E. PY - 2019 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1255 AB - Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of platinum-based chemotherapy and decreases the quality of life of cancer patients. We compared neuroprotective properties of several agents using an in vitro model of terminally differentiated human cells NT2-N derived from cell line NT2/D1. Sodium azide and an active metabolite of amifostine (WR1065) increase cell viability in simultaneous treatment with cisplatin. In addition, WR1065 protects the non-dividing neurons by decreasing cisplatin caused oxidative stress and apoptosis. Accumulation of Pt in cisplatin-treated cells was heterogeneous, but the frequency and concentration of Pt in cells were lowered in the presence of WR1065 as shown by X-ray fluorescence microscopy (XFM). Transition metals accumulation accompanied Pt increase in cells; this effect was equally diminished in the presence of WR1065. To analyze possible chemical modulation of Pt-DNA bonds, we examined the platinum L-III near edge spectrum by X-ray absorption spectroscopy. The spectrum found in cisplatin-DNA samples is altered differently by the addition of either WR1065 or sodium azide. Importantly, a similar change in Pt edge spectra was noted in cells treated with cisplatin and WR1065. Therefore, amifostine should be reconsidered as a candidate for treatments that reduce or prevent CIPN. PB - Springer/Plenum Publishers, New York T2 - Cellular and Molecular Neurobiology T1 - Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro EP - 636 IS - 5 SP - 619 VL - 39 DO - 10.1007/s10571-019-00667-7 ER -
@article{ author = "Popović, Jelena and Lazić, Andrijana and Paunesku, Tatjana and Ma, Qing and Chen, Si and Lai, Barry and Stevanović, Milena and Woloschak, Gayle E.", year = "2019", abstract = "Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of platinum-based chemotherapy and decreases the quality of life of cancer patients. We compared neuroprotective properties of several agents using an in vitro model of terminally differentiated human cells NT2-N derived from cell line NT2/D1. Sodium azide and an active metabolite of amifostine (WR1065) increase cell viability in simultaneous treatment with cisplatin. In addition, WR1065 protects the non-dividing neurons by decreasing cisplatin caused oxidative stress and apoptosis. Accumulation of Pt in cisplatin-treated cells was heterogeneous, but the frequency and concentration of Pt in cells were lowered in the presence of WR1065 as shown by X-ray fluorescence microscopy (XFM). Transition metals accumulation accompanied Pt increase in cells; this effect was equally diminished in the presence of WR1065. To analyze possible chemical modulation of Pt-DNA bonds, we examined the platinum L-III near edge spectrum by X-ray absorption spectroscopy. The spectrum found in cisplatin-DNA samples is altered differently by the addition of either WR1065 or sodium azide. Importantly, a similar change in Pt edge spectra was noted in cells treated with cisplatin and WR1065. Therefore, amifostine should be reconsidered as a candidate for treatments that reduce or prevent CIPN.", publisher = "Springer/Plenum Publishers, New York", journal = "Cellular and Molecular Neurobiology", title = "Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro", pages = "636-619", number = "5", volume = "39", doi = "10.1007/s10571-019-00667-7" }
Popović, J., Lazić, A., Paunesku, T., Ma, Q., Chen, S., Lai, B., Stevanović, M.,& Woloschak, G. E.. (2019). Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro. in Cellular and Molecular Neurobiology Springer/Plenum Publishers, New York., 39(5), 619-636. https://doi.org/10.1007/s10571-019-00667-7
Popović J, Lazić A, Paunesku T, Ma Q, Chen S, Lai B, Stevanović M, Woloschak GE. Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro. in Cellular and Molecular Neurobiology. 2019;39(5):619-636. doi:10.1007/s10571-019-00667-7 .
Popović, Jelena, Lazić, Andrijana, Paunesku, Tatjana, Ma, Qing, Chen, Si, Lai, Barry, Stevanović, Milena, Woloschak, Gayle E., "Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro" in Cellular and Molecular Neurobiology, 39, no. 5 (2019):619-636, https://doi.org/10.1007/s10571-019-00667-7 . .