Growth inhibition and toxicity assessments of cis-3,4-diaryl-α-methylene-γ-butyrolactams in cultured human renal cancer cells and zebrafish embryos

Adam Shih-Yuan Lee; Ta-Hsien Lin; Yen-Yu Liu; Yun-Hsin Wang; Shu-Chun Cheng; Tao-Sheng Li; Chiao-Yin Sun; Yau-Hung Chen

doi:10.1016/j.bbagen.2025.130761

Growth inhibition and toxicity assessments of cis-3,4-diaryl-α-methylene-γ-butyrolactams in cultured human renal cancer cells and zebrafish embryos

Biochim Biophys Acta Gen Subj. 2025 Jan 7:130761. doi: 10.1016/j.bbagen.2025.130761. Online ahead of print.

Authors

Adam Shih-Yuan Lee¹, Ta-Hsien Lin², Yen-Yu Liu¹, Yun-Hsin Wang¹, Shu-Chun Cheng³, Tao-Sheng Li⁴, Chiao-Yin Sun⁵, Yau-Hung Chen⁶

Affiliations

¹ Department of Chemistry, Tamkang University, 151, Yingzhuan Road, Danshui Dist., New Taipei City 25137, Taiwan.
² Division of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Biochemistry and Molecular Biology, National Ying Ming Chiao Tung University, Taipei, Taiwan.
³ Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan.
⁴ Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, Japan.
⁵ Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan; College of Medicine, Chang Gung University, Taoyuan 333, Taiwan. Electronic address: [email protected].
⁶ Department of Chemistry, Tamkang University, 151, Yingzhuan Road, Danshui Dist., New Taipei City 25137, Taiwan. Electronic address: [email protected].

PMID: 39788219
DOI: 10.1016/j.bbagen.2025.130761

Abstract

This study aimed to compare and evaluate the growth inhibition effects of eight previously synthesized compounds, cis-3,4-diaryl-α-methylene-γ-butyrolactams (compounds 1-8), on two human renal carcinoma cell (RCC) lines: CRL-1932 (rapid growth) and HTB-44 (slow growth). MTT assays and flow cytometry were conducted, revealing that compounds 5 and 6 had the potential to induce cell death in the slow-growing RCC cells (HTB-44), while compound 8 demonstrated effectiveness in both RCC lines (HTB-44 and CRL-1932). Additionally, a non-transformed HEK293 cell line and a transgenic zebrafish with a green fluorescent kidney Tg(wt1b:egfp) were used to assess the toxicities of compounds 5, 6, and 8. The findings suggested that compound 8 was relatively non-toxic compared to the others. Western blot analysis indicated that compounds 5, 6, and 8 may interact with the P53/mTOR pathways. Based on these results, we concluded that compound 8 exhibits RCC growth inhibition properties and has lower toxicity, making it a candidate for further investigation in mammalian models.

Keywords: Butyrolactams; Renal cell carcinoma; Zebrafish.