Fenretinide: a novel treatment for endometrial cancer.
Resistance to progestin treatment is a major hurdle in the treatment of advanced and reoccurring endometrial cancer. Fenretinide is a synthetic retinoid that has been evaluated in clinical trials as a cancer therapeutic and chemo-preventive agent. Fenretinide has been established to be cytotoxic to...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4207704?pdf=render |
| _version_ | 1818308988316418048 |
|---|---|
| author | Navdha Mittal Saurabh Malpani Matthew Dyson Masanori Ono John S Coon Julie J Kim Julian C Schink Serdar E Bulun Mary Ellen Pavone |
| author_facet | Navdha Mittal Saurabh Malpani Matthew Dyson Masanori Ono John S Coon Julie J Kim Julian C Schink Serdar E Bulun Mary Ellen Pavone |
| author_sort | Navdha Mittal |
| collection | DOAJ |
| description | Resistance to progestin treatment is a major hurdle in the treatment of advanced and reoccurring endometrial cancer. Fenretinide is a synthetic retinoid that has been evaluated in clinical trials as a cancer therapeutic and chemo-preventive agent. Fenretinide has been established to be cytotoxic to many kinds of cancer cells. In the present study, we demonstrate that fenretinide decreased cell viability and induced apoptosis in Ishikawa cells, which are an endometrial cancer cell line, in dose dependent manner in-vitro. This effect was found to be independent of retinoic acid nuclear receptor signaling pathway. Further, we have shown that this induction of apoptosis by fenretinide may be caused by increased retinol uptake via STRA6. Silencing of STRA6 was shown to decrease apoptosis which was inhibited by knockdown of STRA6 expression in Ishikawa cells. Results of an in-vivo study demonstrated that intraperitoneal injections of fenretinide in endometrial cancer tumors (created using Ishikawa cells) in mice inhibited tumor growth effectively. Immunohistochemistry of mice tumors showed a decrease in Ki67 expression and an increase in cleaved caspase-3 staining after fenretinide treatment when compared to vehicle treated mice. Collectively, our results are the first to establish the efficacy of fenretinide as an antitumor agent for endometrial cancer both in-vitro and in-vivo, providing a valuable rationale for initiating more preclinical studies and clinical trials using fenretinide for the treatment of endometrial cancer. |
| first_indexed | 2024-12-13T07:23:01Z |
| format | Article |
| id | doaj.art-f58977ee9afa495bb5d45984ddfced80 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T07:23:01Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f58977ee9afa495bb5d45984ddfced802022-12-21T23:55:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01910e11041010.1371/journal.pone.0110410Fenretinide: a novel treatment for endometrial cancer.Navdha MittalSaurabh MalpaniMatthew DysonMasanori OnoJohn S CoonJulie J KimJulian C SchinkSerdar E BulunMary Ellen PavoneResistance to progestin treatment is a major hurdle in the treatment of advanced and reoccurring endometrial cancer. Fenretinide is a synthetic retinoid that has been evaluated in clinical trials as a cancer therapeutic and chemo-preventive agent. Fenretinide has been established to be cytotoxic to many kinds of cancer cells. In the present study, we demonstrate that fenretinide decreased cell viability and induced apoptosis in Ishikawa cells, which are an endometrial cancer cell line, in dose dependent manner in-vitro. This effect was found to be independent of retinoic acid nuclear receptor signaling pathway. Further, we have shown that this induction of apoptosis by fenretinide may be caused by increased retinol uptake via STRA6. Silencing of STRA6 was shown to decrease apoptosis which was inhibited by knockdown of STRA6 expression in Ishikawa cells. Results of an in-vivo study demonstrated that intraperitoneal injections of fenretinide in endometrial cancer tumors (created using Ishikawa cells) in mice inhibited tumor growth effectively. Immunohistochemistry of mice tumors showed a decrease in Ki67 expression and an increase in cleaved caspase-3 staining after fenretinide treatment when compared to vehicle treated mice. Collectively, our results are the first to establish the efficacy of fenretinide as an antitumor agent for endometrial cancer both in-vitro and in-vivo, providing a valuable rationale for initiating more preclinical studies and clinical trials using fenretinide for the treatment of endometrial cancer.http://europepmc.org/articles/PMC4207704?pdf=render |
| spellingShingle | Navdha Mittal Saurabh Malpani Matthew Dyson Masanori Ono John S Coon Julie J Kim Julian C Schink Serdar E Bulun Mary Ellen Pavone Fenretinide: a novel treatment for endometrial cancer. PLoS ONE |
| title | Fenretinide: a novel treatment for endometrial cancer. |
| title_full | Fenretinide: a novel treatment for endometrial cancer. |
| title_fullStr | Fenretinide: a novel treatment for endometrial cancer. |
| title_full_unstemmed | Fenretinide: a novel treatment for endometrial cancer. |
| title_short | Fenretinide: a novel treatment for endometrial cancer. |
| title_sort | fenretinide a novel treatment for endometrial cancer |
| url | http://europepmc.org/articles/PMC4207704?pdf=render |
| work_keys_str_mv | AT navdhamittal fenretinideanoveltreatmentforendometrialcancer AT saurabhmalpani fenretinideanoveltreatmentforendometrialcancer AT matthewdyson fenretinideanoveltreatmentforendometrialcancer AT masanoriono fenretinideanoveltreatmentforendometrialcancer AT johnscoon fenretinideanoveltreatmentforendometrialcancer AT juliejkim fenretinideanoveltreatmentforendometrialcancer AT juliancschink fenretinideanoveltreatmentforendometrialcancer AT serdarebulun fenretinideanoveltreatmentforendometrialcancer AT maryellenpavone fenretinideanoveltreatmentforendometrialcancer |