Anticancer Effect of Heparin–Taurocholate Conjugate on Orthotopically Induced Exocrine and Endocrine Pancreatic Cancer

Pancreatic cancers are classified based on where they occur, and are grouped into those derived from exocrine and those derived from neuroendocrine tumors, thereby experiencing different anticancer effects under medication. Therefore, it is necessary to develop anticancer drugs that can inhibit both...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hae Hyun Hwang, Hee Jeong Jeong, Sangwu Yun, Youngro Byun, Teruo Okano, Sung Wan Kim, Dong Yun Lee
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	heparin taurocholate conjugate pancreatic cancer cell anticancer antiangiogenesis orthotopic animal Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a41277895e6040ba92a1a781055cc238
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a41277895e6040ba92a1a781055cc238
record_format	dspace
spelling	oai:doaj.org-article:a41277895e6040ba92a1a781055cc2382021-11-25T17:03:51ZAnticancer Effect of Heparin–Taurocholate Conjugate on Orthotopically Induced Exocrine and Endocrine Pancreatic Cancer10.3390/cancers132257752072-6694https://doaj.org/article/a41277895e6040ba92a1a781055cc2382021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5775https://doaj.org/toc/2072-6694Pancreatic cancers are classified based on where they occur, and are grouped into those derived from exocrine and those derived from neuroendocrine tumors, thereby experiencing different anticancer effects under medication. Therefore, it is necessary to develop anticancer drugs that can inhibit both types. To this end, we developed a heparin–taurocholate conjugate, i.e., LHT, to suppress tumor growth via its antiangiogenic activity. Here, we conducted a study to determine the anticancer efficacy of LHT on pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumor (PNET), in an orthotopic animal model. LHT reduced not only proliferation of cancer cells, but also attenuated the production of VEGF through ERK dephosphorylation. LHT effectively reduced the migration, invasion and tube formation of endothelial cells via dephosphorylation of VEGFR, ERK1/2, and FAK protein. Especially, these effects of LHT were much stronger on PNET (RINm cells) than PDAC (PANC1 and MIA PaCa-2 cells). Eventually, LHT reduced ~50% of the tumor weights and tumor volumes of all three cancer cells in the orthotopic model, via antiproliferation of cancer cells and antiangiogenesis of endothelial cells. Interestingly, LHT had a more dominant effect in the PNET-induced tumor model than in PDAC in vivo. Collectively, these findings demonstrated that LHT could be a potential antipancreatic cancer medication, regardless of pancreatic cancer types.Hae Hyun HwangHee Jeong JeongSangwu YunYoungro ByunTeruo OkanoSung Wan KimDong Yun LeeMDPI AGarticleheparin taurocholate conjugatepancreatic cancer cellanticancerantiangiogenesisorthotopic animalNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5775, p 5775 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	heparin taurocholate conjugate pancreatic cancer cell anticancer antiangiogenesis orthotopic animal Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	heparin taurocholate conjugate pancreatic cancer cell anticancer antiangiogenesis orthotopic animal Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Hae Hyun Hwang Hee Jeong Jeong Sangwu Yun Youngro Byun Teruo Okano Sung Wan Kim Dong Yun Lee Anticancer Effect of Heparin–Taurocholate Conjugate on Orthotopically Induced Exocrine and Endocrine Pancreatic Cancer
description	Pancreatic cancers are classified based on where they occur, and are grouped into those derived from exocrine and those derived from neuroendocrine tumors, thereby experiencing different anticancer effects under medication. Therefore, it is necessary to develop anticancer drugs that can inhibit both types. To this end, we developed a heparin–taurocholate conjugate, i.e., LHT, to suppress tumor growth via its antiangiogenic activity. Here, we conducted a study to determine the anticancer efficacy of LHT on pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumor (PNET), in an orthotopic animal model. LHT reduced not only proliferation of cancer cells, but also attenuated the production of VEGF through ERK dephosphorylation. LHT effectively reduced the migration, invasion and tube formation of endothelial cells via dephosphorylation of VEGFR, ERK1/2, and FAK protein. Especially, these effects of LHT were much stronger on PNET (RINm cells) than PDAC (PANC1 and MIA PaCa-2 cells). Eventually, LHT reduced ~50% of the tumor weights and tumor volumes of all three cancer cells in the orthotopic model, via antiproliferation of cancer cells and antiangiogenesis of endothelial cells. Interestingly, LHT had a more dominant effect in the PNET-induced tumor model than in PDAC in vivo. Collectively, these findings demonstrated that LHT could be a potential antipancreatic cancer medication, regardless of pancreatic cancer types.
format	article
author	Hae Hyun Hwang Hee Jeong Jeong Sangwu Yun Youngro Byun Teruo Okano Sung Wan Kim Dong Yun Lee
author_facet	Hae Hyun Hwang Hee Jeong Jeong Sangwu Yun Youngro Byun Teruo Okano Sung Wan Kim Dong Yun Lee
author_sort	Hae Hyun Hwang
title	Anticancer Effect of Heparin–Taurocholate Conjugate on Orthotopically Induced Exocrine and Endocrine Pancreatic Cancer
title_short	Anticancer Effect of Heparin–Taurocholate Conjugate on Orthotopically Induced Exocrine and Endocrine Pancreatic Cancer
title_full	Anticancer Effect of Heparin–Taurocholate Conjugate on Orthotopically Induced Exocrine and Endocrine Pancreatic Cancer
title_fullStr	Anticancer Effect of Heparin–Taurocholate Conjugate on Orthotopically Induced Exocrine and Endocrine Pancreatic Cancer
title_full_unstemmed	Anticancer Effect of Heparin–Taurocholate Conjugate on Orthotopically Induced Exocrine and Endocrine Pancreatic Cancer
title_sort	anticancer effect of heparin–taurocholate conjugate on orthotopically induced exocrine and endocrine pancreatic cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a41277895e6040ba92a1a781055cc238
work_keys_str_mv	AT haehyunhwang anticancereffectofheparintaurocholateconjugateonorthotopicallyinducedexocrineandendocrinepancreaticcancer AT heejeongjeong anticancereffectofheparintaurocholateconjugateonorthotopicallyinducedexocrineandendocrinepancreaticcancer AT sangwuyun anticancereffectofheparintaurocholateconjugateonorthotopicallyinducedexocrineandendocrinepancreaticcancer AT youngrobyun anticancereffectofheparintaurocholateconjugateonorthotopicallyinducedexocrineandendocrinepancreaticcancer AT teruookano anticancereffectofheparintaurocholateconjugateonorthotopicallyinducedexocrineandendocrinepancreaticcancer AT sungwankim anticancereffectofheparintaurocholateconjugateonorthotopicallyinducedexocrineandendocrinepancreaticcancer AT dongyunlee anticancereffectofheparintaurocholateconjugateonorthotopicallyinducedexocrineandendocrinepancreaticcancer
_version_	1718412793581928448

Anticancer Effect of Heparin–Taurocholate Conjugate on Orthotopically Induced Exocrine and Endocrine Pancreatic Cancer

Ejemplares similares