Therapeutic effects of an innovative BS-HH-002 drug on pancreatic cancer cells via induction of complete MCL-1 degradation

BS-HH-002 is a newly developed drug with excellent antitumor activity, which resulted from the modification and optimization of the side structure of the homoharringtonine (HHT). It is particularly efficient in treatment for acute myeloid leukemia and myelodysplastic syndromes. Here we tested whethe...

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Autores principales:	A-min Wang, Ru Qiu, Duo Zhang, Xiao-yan Zhao
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	BS-HH-002 HHT MCL-1 JAK-STAT Pancreatic cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/231c77d285804f20be384019be5cc7d2
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spelling	oai:doaj.org-article:231c77d285804f20be384019be5cc7d22021-11-28T04:29:54ZTherapeutic effects of an innovative BS-HH-002 drug on pancreatic cancer cells via induction of complete MCL-1 degradation1936-523310.1016/j.tranon.2021.101288https://doaj.org/article/231c77d285804f20be384019be5cc7d22022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1936523321002795https://doaj.org/toc/1936-5233BS-HH-002 is a newly developed drug with excellent antitumor activity, which resulted from the modification and optimization of the side structure of the homoharringtonine (HHT). It is particularly efficient in treatment for acute myeloid leukemia and myelodysplastic syndromes. Here we tested whether BS-HH-002 also had anti-cancer effects on solid tumors, especially pancreatic cancer. The results showed that BS-HH-002 treatment resulted in the complete degradation of the anti-apoptosis protein MCL-1, thereby inhibiting proliferation and inducing apoptosis of pancreatic cancer cells. In contrast, BCL-2 and BCL-XL protein levels were still detected in apoptotic cells. Further, we compared HHT and BS-HH-002 in terms of PK and heart toxicity in animals. Compared to HHT, BS-HH-002 quickly reached high blood concentration after intravenous injection or oral administration, without causing obvious cardiac toxicity. These results indicate that BS-HH-002 is a promising new anti-cancer drug to treat pancreatic and other solid tumors.A-min WangRu QiuDuo ZhangXiao-yan ZhaoElsevierarticleBS-HH-002HHTMCL-1JAK-STATPancreatic cancerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENTranslational Oncology, Vol 15, Iss 1, Pp 101288- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	BS-HH-002 HHT MCL-1 JAK-STAT Pancreatic cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	BS-HH-002 HHT MCL-1 JAK-STAT Pancreatic cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 A-min Wang Ru Qiu Duo Zhang Xiao-yan Zhao Therapeutic effects of an innovative BS-HH-002 drug on pancreatic cancer cells via induction of complete MCL-1 degradation
description	BS-HH-002 is a newly developed drug with excellent antitumor activity, which resulted from the modification and optimization of the side structure of the homoharringtonine (HHT). It is particularly efficient in treatment for acute myeloid leukemia and myelodysplastic syndromes. Here we tested whether BS-HH-002 also had anti-cancer effects on solid tumors, especially pancreatic cancer. The results showed that BS-HH-002 treatment resulted in the complete degradation of the anti-apoptosis protein MCL-1, thereby inhibiting proliferation and inducing apoptosis of pancreatic cancer cells. In contrast, BCL-2 and BCL-XL protein levels were still detected in apoptotic cells. Further, we compared HHT and BS-HH-002 in terms of PK and heart toxicity in animals. Compared to HHT, BS-HH-002 quickly reached high blood concentration after intravenous injection or oral administration, without causing obvious cardiac toxicity. These results indicate that BS-HH-002 is a promising new anti-cancer drug to treat pancreatic and other solid tumors.
format	article
author	A-min Wang Ru Qiu Duo Zhang Xiao-yan Zhao
author_facet	A-min Wang Ru Qiu Duo Zhang Xiao-yan Zhao
author_sort	A-min Wang
title	Therapeutic effects of an innovative BS-HH-002 drug on pancreatic cancer cells via induction of complete MCL-1 degradation
title_short	Therapeutic effects of an innovative BS-HH-002 drug on pancreatic cancer cells via induction of complete MCL-1 degradation
title_full	Therapeutic effects of an innovative BS-HH-002 drug on pancreatic cancer cells via induction of complete MCL-1 degradation
title_fullStr	Therapeutic effects of an innovative BS-HH-002 drug on pancreatic cancer cells via induction of complete MCL-1 degradation
title_full_unstemmed	Therapeutic effects of an innovative BS-HH-002 drug on pancreatic cancer cells via induction of complete MCL-1 degradation
title_sort	therapeutic effects of an innovative bs-hh-002 drug on pancreatic cancer cells via induction of complete mcl-1 degradation
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/231c77d285804f20be384019be5cc7d2
work_keys_str_mv	AT aminwang therapeuticeffectsofaninnovativebshh002drugonpancreaticcancercellsviainductionofcompletemcl1degradation AT ruqiu therapeuticeffectsofaninnovativebshh002drugonpancreaticcancercellsviainductionofcompletemcl1degradation AT duozhang therapeuticeffectsofaninnovativebshh002drugonpancreaticcancercellsviainductionofcompletemcl1degradation AT xiaoyanzhao therapeuticeffectsofaninnovativebshh002drugonpancreaticcancercellsviainductionofcompletemcl1degradation
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Therapeutic effects of an innovative BS-HH-002 drug on pancreatic cancer cells via induction of complete MCL-1 degradation

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