Evaluation of STAT3 Inhibition by Cancer Chemopreventive Trichothecenes Derived from Metabolites of Trichothecium roseum

IF 1.5 4区医学 Q4 CHEMISTRY, MEDICINAL Chemical & pharmaceutical bulletin Pub Date : 2024-07-23 DOI:10.1248/cpb.c24-00300

Mitsuaki Yamashita, Akari Nakanishi, Chiehming Chang, Kosei Tsurushima, Kiyoshige Nakamoto, Akira Iida

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Abstract

This study evaluated the ability of isolated or semisynthesized trichothecene sesquiterpenes to prevent cancer emergence and proliferation and inhibit signal transducer and activator of transcription-3 (STAT3) phosphorylation through in vitro assays. Trichothecinol A (TTC-A), which bears a hydroxy group at C3, exhibited greater cancer prevention, antiproliferation, and STAT3 phosphorylation inhibition effects than trichothecin (TTC), which lacks a hydroxy group at C3. Furthermore, trichothecinol B (TTC-B), which is a reduced derivative of TTC and has similar cytotoxic effect, showed substantially weaker chemoprotection and STAT3 phosphorylation inhibition effects than TTC. These results clearly indicate that the hydroxy group at C3 and carbonyl group at C8 are crucial for inducing both potent chemoprevention and STAT3 phosphorylation inhibition.

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评估从单端孢霉烯代谢物中提取的具有癌症化学预防作用的单端孢霉烯对 STAT3 的抑制作用

本研究通过体外试验评估了分离或半合成单端孢霉烯倍半萜防止癌症出现和增殖以及抑制信号转导和激活转录-3（STAT3）磷酸化的能力。与 C3 上缺少羟基的单端孢霉烯（TTC）相比，C3 上带有羟基的单端孢霉烯 A（TTC-A）具有更强的防癌、抗增殖和 STAT3 磷酸化抑制作用。此外，单端孢霉烯醇 B（TTC-B）是 TTC 的还原衍生物，具有类似的细胞毒性作用，但其化学保护和 STAT3 磷酸化抑制作用大大弱于 TTC。这些结果清楚地表明，C3 处的羟基和 C8 处的羰基是诱导强效化学防护和 STAT3 磷酸化抑制的关键。

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来源期刊

Chemical & pharmaceutical bulletin 医学-化学综合

CiteScore

3.20

自引率

5.90%

发文量

132

审稿时长

1.7 months

期刊介绍： The CPB covers various chemical topics in the pharmaceutical and health sciences fields dealing with biologically active compounds, natural products, and medicines, while BPB deals with a wide range of biological topics in the pharmaceutical and health sciences fields including scientific research from basic to clinical studies. For details of their respective scopes, please refer to the submission topic categories below. Topics: Organic chemistry In silico science Inorganic chemistry Pharmacognosy Health statistics Forensic science Biochemistry Pharmacology Pharmaceutical care and science Medicinal chemistry Analytical chemistry Physical pharmacy Natural product chemistry Toxicology Environmental science Molecular and cellular biology Biopharmacy and pharmacokinetics Pharmaceutical education Chemical biology Physical chemistry Pharmaceutical engineering Epidemiology Hygiene Regulatory science Immunology and microbiology Clinical pharmacy Miscellaneous.