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

doi:10.1016/j.bbagen.2025.130761

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Title:	Growth inhibition and toxicity assessments of cis-3,4-diaryl-α-methylene-γ-butyrolactams in cultured human renal cancer cells and zebrafish embryos
Authors:	Lee, Adam Shih-Yuan;Lin, Ta-Hsien;Liu, Yen-Yu;Wang, Yun-Hsin;Cheng, Shu-Chun;Li, Tao-Sheng;Sun, Chiao-Yin;Chen, Yau-Hung
Keywords:	Butyrolactams;Renal cell carcinoma;Zebrafish
Date:	2025-01-07
Issue Date:	2025-03-20 09:33:06 (UTC+8)
Publisher:	Elsvier
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.
Relation:	Biochimica et Biophysica Acta
DOI:	10.1016/j.bbagen.2025.130761
Appears in Collections:	[Graduate Institute & Department of Chemistry] Journal Article

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