一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Cell Death & Disease >>article
Cell Death & Disease

Cell Death & Disease

IF: 8.1
Download PDF

Potentiation of apoptosis in drug-resistant mantle cell lymphoma cells by MCL-1 inhibitor involves downregulation of inhibitor of apoptosis proteins.

Published:2 November 2023 DOI: 10.1038/s41419-023-06233-w PMID: 37919300
Yijing Li, Heng-Huan Lee, Vivian Changying Jiang, Yuxuan Che, Joseph McIntosh, Alexa Jordan, Jovanny Vargas, Tianci Zhang, Fangfang Yan, Margaret Elizabeth Simmons, Wei Wang, Lei Nie, Yixin Yao, Preetesh Jain, Michael Wang, Yang Liu

Abstract

Bruton's tyrosine kinase inhibitors (BTKi) and CAR T-cell therapy have demonstrated tremendous clinical benefits in mantle cell lymphoma (MCL) patients, but intrinsic or acquired resistance inevitably develops. In this study, we assessed the efficacy of the highly potent and selective MCL-1 inhibitor AZD5991 in various therapy-resistant MCL cell models. AZD5991 markedly induced apoptosis in these cells. In addition to liberating BAK from the antiapoptotic MCL-1/BAK complex for the subsequent apoptosis cascade, AZD5991 downregulated inhibitor of apoptosis proteins (IAPs) through a BAK-dependent mechanism to amplify the apoptotic signal. The combination of AZD5991 with venetoclax enhanced apoptosis and reduced mitochondrial oxygen consumption capacity in MCL cell lines irrespective of their BTKi or venetoclax sensitivity. This combination also dramatically inhibited tumor growth and prolonged mouse survival in two aggressive MCL patient-derived xenograft models. Mechanistically, the augmented cell lethality was accompanied by the synergistic suppression of IAPs. Supporting this notion, the IAP antagonist BV6 induced dramatic apoptosis in resistant MCL cells and sensitized the resistant MCL cells to venetoclax. Our study uncovered another unique route for MCL-1 inhibitor to trigger apoptosis, implying that the pro-apoptotic combination of IAP antagonists and apoptosis inducers could be further exploited for MCL patients with multiple therapeutic resistance.

Substances (14)

Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
BV6 1001600-56-1 C70H96N10O8 115 suppliers $22.00-$2841.00
BV6 1001600-56-1 C70H96N10O8 115 suppliers $22.00-$2841.00
BV6 1001600-56-1 C70H96N10O8 115 suppliers $22.00-$2841.00
BV6 1001600-56-1 C70H96N10O8 115 suppliers $22.00-$2841.00
S63845 1799633-27-4 C39H37ClF4N6O6S 111 suppliers $56.00-$6500.00
S63845 1799633-27-4 C39H37ClF4N6O6S 111 suppliers $56.00-$6500.00
S63845 1799633-27-4 C39H37ClF4N6O6S 111 suppliers $56.00-$6500.00
S63845 1799633-27-4 C39H37ClF4N6O6S 111 suppliers $56.00-$6500.00
MIK665 1799631-75-6 C47H44ClFN6O6S 82 suppliers Inquiry
MIK665 1799631-75-6 C47H44ClFN6O6S 82 suppliers Inquiry

Similar articles

IF:4.6

Clinical Pharmacology of Brigatinib: A Next-Generation Anaplastic Lymphoma Kinase Inhibitor.

Clinical Pharmacokinetics Neeraj Gupta, Michael J Hanley,etc Published: 1 August 2023
泸水县| 福清市| 郎溪县| 华蓥市| 齐齐哈尔市| 白朗县| 万安县| 天全县| 巴林左旗| 友谊县| 咸丰县| 绵阳市| 恩平市| 聂荣县| 泗水县| 木兰县| 公主岭市| 闻喜县| 新乡县| 九龙县| 肥西县| 堆龙德庆县| 嘉义市| 清原| 盖州市| 电白县| 平乐县| 迁安市| 如东县| 永川市| 噶尔县| 河间市| 根河市| 略阳县| 哈密市| 饶河县| 河曲县| 盐津县| 开平市| 华亭县| 阳曲县|