Estrogen Receptor Beta Selective Agonists as Agents to Treat Chemotherapeutic-Induced Neuropathic Pain
Ma, Jian Nong ; McFarland, Krista ; Olsson, Roger LU
and Burstein, Ethan S.
(2016)
In ACS Chemical Neuroscience
7(9).
p.1180-1187
- Abstract
Chemotherapy-induced neuropathic pain (CINP) remains a major unmet medical need. Estrogen receptor beta (ERβ)-selective agonists represent a novel strategy for treating CINP because they are neuroprotective and may also have anticancer activity. We confirmed that ERβ-selective agonists have antiallodynic effects in the spinal nerve ligation model of neuropathic pain. We then showed that structurally diverse ERβ-selective agonists also relieved allodynia in CINP caused by taxol, oxaliplatin, and vincristine. These effects were receptor subtype specific and mediated by ERβ receptors as ERα-selective and nonselective estrogen agonists were inactive, a mixture of an ERβ and ERα agonist was inactive, and ERβ-selective antagonists blocked the... (More)
Chemotherapy-induced neuropathic pain (CINP) remains a major unmet medical need. Estrogen receptor beta (ERβ)-selective agonists represent a novel strategy for treating CINP because they are neuroprotective and may also have anticancer activity. We confirmed that ERβ-selective agonists have antiallodynic effects in the spinal nerve ligation model of neuropathic pain. We then showed that structurally diverse ERβ-selective agonists also relieved allodynia in CINP caused by taxol, oxaliplatin, and vincristine. These effects were receptor subtype specific and mediated by ERβ receptors as ERα-selective and nonselective estrogen agonists were inactive, a mixture of an ERβ and ERα agonist was inactive, and ERβ-selective antagonists blocked the effects of the ERβ-selective agonists. The efficacy and potency of ERβ-agonists was greater in male rats than females. To address the possibility that AC-186 might stimulate proliferation of cancers, rendering it unsuitable for treating CINP, we evaluated proliferative effects of AC-186 on prostate cancer cells and found it inhibited growth (LNCaP cells) or had no effect (PC3 cells) on these cells. Thus, ERβ-selective agonists exhibit potential for treating CINP.
(Less)
- author
- Ma, Jian Nong
; McFarland, Krista
; Olsson, Roger
LU
and Burstein, Ethan S.
- organization
- publishing date
- 2016-09-21
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- chemotherapy, estrogen receptor beta, Neuropathic pain, oxaliplatin, taxol, vincristine
- in
- ACS Chemical Neuroscience
- volume
- 7
- issue
- 9
- pages
- 8 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:27456785
- wos:000384041000004
- scopus:84988649533
- ISSN
- 1948-7193
- DOI
- 10.1021/acschemneuro.6b00183
- language
- English
- LU publication?
- yes
- id
- 01be39df-f5ee-4180-b7ba-b453789d9e5c
- date added to LUP
- 2016-11-01 12:20:39
- date last changed
- 2024-04-05 09:12:55
@article{01be39df-f5ee-4180-b7ba-b453789d9e5c,
abstract = {{<p>Chemotherapy-induced neuropathic pain (CINP) remains a major unmet medical need. Estrogen receptor beta (ERβ)-selective agonists represent a novel strategy for treating CINP because they are neuroprotective and may also have anticancer activity. We confirmed that ERβ-selective agonists have antiallodynic effects in the spinal nerve ligation model of neuropathic pain. We then showed that structurally diverse ERβ-selective agonists also relieved allodynia in CINP caused by taxol, oxaliplatin, and vincristine. These effects were receptor subtype specific and mediated by ERβ receptors as ERα-selective and nonselective estrogen agonists were inactive, a mixture of an ERβ and ERα agonist was inactive, and ERβ-selective antagonists blocked the effects of the ERβ-selective agonists. The efficacy and potency of ERβ-agonists was greater in male rats than females. To address the possibility that AC-186 might stimulate proliferation of cancers, rendering it unsuitable for treating CINP, we evaluated proliferative effects of AC-186 on prostate cancer cells and found it inhibited growth (LNCaP cells) or had no effect (PC3 cells) on these cells. Thus, ERβ-selective agonists exhibit potential for treating CINP.</p>}},
author = {{Ma, Jian Nong and McFarland, Krista and Olsson, Roger and Burstein, Ethan S.}},
issn = {{1948-7193}},
keywords = {{chemotherapy; estrogen receptor beta; Neuropathic pain; oxaliplatin; taxol; vincristine}},
language = {{eng}},
month = {{09}},
number = {{9}},
pages = {{1180--1187}},
publisher = {{The American Chemical Society (ACS)}},
series = {{ACS Chemical Neuroscience}},
title = {{Estrogen Receptor Beta Selective Agonists as Agents to Treat Chemotherapeutic-Induced Neuropathic Pain}},
url = {{http://dx.doi.org/10.1021/acschemneuro.6b00183}},
doi = {{10.1021/acschemneuro.6b00183}},
volume = {{7}},
year = {{2016}},
}