Peptide B targets soluble guanylyl cyclase α1 and kills prostate cancer cells.
Among androgen-regulated genes, soluble guanylyl cyclase α1 (sGCα1) is significant in promoting the survival and growth of prostate cancer cells and does so independent of nitric oxide (NO) signaling. Peptides were designed targeting sGCα1 to block its pro-cancer functions and one peptide is discuss...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5578680?pdf=render |
| _version_ | 1818480515567583232 |
|---|---|
| author | Jun Zhou Shuai Gao Chen-Lin Hsieh Mamata Malla Lirim Shemshedini |
| author_facet | Jun Zhou Shuai Gao Chen-Lin Hsieh Mamata Malla Lirim Shemshedini |
| author_sort | Jun Zhou |
| collection | DOAJ |
| description | Among androgen-regulated genes, soluble guanylyl cyclase α1 (sGCα1) is significant in promoting the survival and growth of prostate cancer cells and does so independent of nitric oxide (NO) signaling. Peptides were designed targeting sGCα1 to block its pro-cancer functions and one peptide is discussed here. Peptide B-8R killed both androgen-dependent and androgen-independent prostate cancer cells that expressed sGCα1, but not cells that do not express this gene. Peptide B-8R induced apoptosis of prostate cancer cells. Importantly, Peptide B-8R does not affect nor its cytotoxicity depend on NO signaling, despite the fact that it associates with sGCα1, which dimerizes with sGCβ1 to form the sGC enzyme. Just as with a previously studied Peptide A-8R, Peptide B-8R induced elevated levels of reactive oxygen species (ROS) in prostate cancer cells, but using a ROS-sequestering agent showed that ROS was not responsible the cytotoxic activity of Peptide B-8R. Interestingly, Peptide B-8R induced elevated levels of p53 and phosphorylated p38, but neither of these changes is the cause of the peptide's cytotoxicity. Additional drugs were used to alter levels of iron levels in cells and these studies showed that Peptide B-8R activity does not depend on Ferroptosis. Thus, future work will be directed at defining the mechanism of cytotoxic action of Peptide B-8R against prostate cancer cells. |
| first_indexed | 2024-12-10T11:24:42Z |
| format | Article |
| id | doaj.art-42f7b571b2704f1aa39e826b7077e042 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T11:24:42Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-42f7b571b2704f1aa39e826b7077e0422022-12-22T01:50:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01128e018408810.1371/journal.pone.0184088Peptide B targets soluble guanylyl cyclase α1 and kills prostate cancer cells.Jun ZhouShuai GaoChen-Lin HsiehMamata MallaLirim ShemshediniAmong androgen-regulated genes, soluble guanylyl cyclase α1 (sGCα1) is significant in promoting the survival and growth of prostate cancer cells and does so independent of nitric oxide (NO) signaling. Peptides were designed targeting sGCα1 to block its pro-cancer functions and one peptide is discussed here. Peptide B-8R killed both androgen-dependent and androgen-independent prostate cancer cells that expressed sGCα1, but not cells that do not express this gene. Peptide B-8R induced apoptosis of prostate cancer cells. Importantly, Peptide B-8R does not affect nor its cytotoxicity depend on NO signaling, despite the fact that it associates with sGCα1, which dimerizes with sGCβ1 to form the sGC enzyme. Just as with a previously studied Peptide A-8R, Peptide B-8R induced elevated levels of reactive oxygen species (ROS) in prostate cancer cells, but using a ROS-sequestering agent showed that ROS was not responsible the cytotoxic activity of Peptide B-8R. Interestingly, Peptide B-8R induced elevated levels of p53 and phosphorylated p38, but neither of these changes is the cause of the peptide's cytotoxicity. Additional drugs were used to alter levels of iron levels in cells and these studies showed that Peptide B-8R activity does not depend on Ferroptosis. Thus, future work will be directed at defining the mechanism of cytotoxic action of Peptide B-8R against prostate cancer cells.http://europepmc.org/articles/PMC5578680?pdf=render |
| spellingShingle | Jun Zhou Shuai Gao Chen-Lin Hsieh Mamata Malla Lirim Shemshedini Peptide B targets soluble guanylyl cyclase α1 and kills prostate cancer cells. PLoS ONE |
| title | Peptide B targets soluble guanylyl cyclase α1 and kills prostate cancer cells. |
| title_full | Peptide B targets soluble guanylyl cyclase α1 and kills prostate cancer cells. |
| title_fullStr | Peptide B targets soluble guanylyl cyclase α1 and kills prostate cancer cells. |
| title_full_unstemmed | Peptide B targets soluble guanylyl cyclase α1 and kills prostate cancer cells. |
| title_short | Peptide B targets soluble guanylyl cyclase α1 and kills prostate cancer cells. |
| title_sort | peptide b targets soluble guanylyl cyclase α1 and kills prostate cancer cells |
| url | http://europepmc.org/articles/PMC5578680?pdf=render |
| work_keys_str_mv | AT junzhou peptidebtargetssolubleguanylylcyclasea1andkillsprostatecancercells AT shuaigao peptidebtargetssolubleguanylylcyclasea1andkillsprostatecancercells AT chenlinhsieh peptidebtargetssolubleguanylylcyclasea1andkillsprostatecancercells AT mamatamalla peptidebtargetssolubleguanylylcyclasea1andkillsprostatecancercells AT lirimshemshedini peptidebtargetssolubleguanylylcyclasea1andkillsprostatecancercells |