Design, synthesis, and biological evaluation of novel HSP27 inhibitors to sensitize lung cancer cells to clinically available anticancer agents

Seul Ki Choi, Soo Yeon Hwang, Seulgi Jeon, Hawon Yoo, Joohyun Lee, Jae Ho Shin, Younghwa Na, Youngjoo Kwon, Yun Sil Lee

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Expression of heat shock protein (HSP) correlates with the oncogenic status of malignant cells and plays an important role in tumorigenesis. HSP27 is constitutively expressed at specific stages of cancer development, and several clinical trials have reported correlations between HSP27 expression and tumor progression, metastasis, and chemoresistance in various types of cancer cells. These findings indicate that HSP27 is a major drug target, particularly in chemo-resistant cancers. As part of our ongoing efforts to improve the previously identified J2, a HSP27 cross-linker, we, in this study, report the identification of NK16 as a novel inducer of abnormal HSP27 dimers that did not affect the expression of HSP90 in an NCI-H460 lung cancer cell model. When NCI-H460 cells were treated with NK16 in combination with the anticancer drug cisplatin or paclitaxel, cleavage of PARP and caspase-3 was increased compared to administration of cisplatin or paclitaxel alone. Similar results were obtained in an NCI-H460-xenografted mouse model, in which tumor growth was suppressed more by co-administration of NK16 and paclitaxel than by paclitaxel alone. We propose NK16 as a meaningful strategy to improve the anticancer efficacy of cisplatin and paclitaxel.

Original languageEnglish
Article number106260
JournalBioorganic Chemistry
Volume130
DOIs
StatePublished - Jan 2023

Bibliographical note

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

  • Combination Therapy
  • Heat Shock Protein 27 (HSP27) Inhibitor
  • Non-Small Cell Lung Cancer (NSCLC)
  • Sensitization

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