Peptide Isolated from Leptospermum flavens Sm. Inhibits Human Glutathione Transferases π (hGSTP) Activity and Enhances the Cytotoxicity of Doxorubicin towards HT-29 Cell Line

IF 0.5 4区生物学 Q4 BIOLOGY Biology Bulletin Pub Date : 2024-05-31 DOI:10.1134/s1062359023605001

W. M. Phang, Z. Alias, N. Aminudin

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Abstract

Glutathione transferase Pi (GST-P) reportedly overexpressed markedly in cancer cell lines. It was correlated to the resistance towards drugs used in chemotherapy treatment. The study demonstrated the isolation of peptide as potential inhibitor to the enzyme. Glutathione transferase Pi (GST-P) was purified from human colon adenocarcinoma HT-29 cell line using glutathione (GSH)-affinity chromatography. Active components presence in ethanolic extract (50% ethanol) of leaves Leptospermum flavescens Sm. was shown possessing inhibitory property (IC₅₀ of 0.088 mg/mL) towards GST-P in vitro. Further fractionation using polyamide the 50% methanol in 2% acetic acid eluate possessed an inhibitory property at IC₅₀ of 0.191 mg/mL. In the study the IC₅₀ values of doxorubicin are 0.788 and 0.816 μg/mL on HT-29 and MRC-5 cell lines respectively while IC₅₀ values of cisplatin were at 9.49 and 4.07 μg/mL on HT-29 and MRC-5 cell lines respectively. The 50% methanol eluate has significantly non-toxic to both of the cell lines with 100% cell viability at more than 100 μg/mL sample applied. In combination with doxorubicin, 50% methanol eluate enhanced cytotoxicity of the drug towards HT-29 by reduction of IC₅₀ value significantly to 66%. The eluate however only reduced the IC₅₀ to 11% when combined with cisplatin. The study indicates that the eluate can potentiate cytotoxicity of doxorubicin on HT-29 cell line and this effect is correlated to the ability of the eluate to inhibit GST-P in vitro. The purified active molecule was a peptide with molecular weight of 3.5 kDa.

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从 Leptospermum flavens Sm.抑制人谷胱甘肽转移酶π（hGSTP）活性并增强多柔比星对 HT-29 细胞株的细胞毒性

摘要据报道，谷胱甘肽转移酶 Pi（GST-P）在癌细胞系中明显过表达。它与化疗药物的抗药性有关。该研究证明，分离出的多肽是该酶的潜在抑制剂。使用谷胱甘肽（GSH）亲和色谱法从人类结肠腺癌 HT-29 细胞系中纯化了谷胱甘肽转移酶 Pi（GST-P）。结果表明，Leptospermum flavescens Sm.叶片乙醇提取物（50%乙醇）中的活性成分对体外 GST-P 具有抑制作用（IC50 为 0.088 mg/mL）。使用聚酰胺对 50%甲醇和 2% 乙酸的洗脱液进行进一步分馏，其抑制性的 IC50 值为 0.191 mg/mL。在这项研究中，多柔比星对 HT-29 和 MRC-5 细胞系的 IC50 值分别为 0.788 和 0.816 μg/mL，而顺铂对 HT-29 和 MRC-5 细胞系的 IC50 值分别为 9.49 和 4.07 μg/mL。50%的甲醇洗脱液对这两种细胞株均无明显毒性，在使用超过 100 μg/mL 样品时，细胞存活率为 100%。在与多柔比星联合使用时，50% 甲醇洗脱液增强了该药物对 HT-29 的细胞毒性，将 IC50 值大幅降低至 66%。然而，当洗脱液与顺铂结合使用时，其 IC50 值仅降低了 11%。研究表明，洗脱液能增强多柔比星对 HT-29 细胞株的细胞毒性，而这种作用与洗脱液在体外抑制 GST-P 的能力有关。纯化的活性分子是分子量为 3.5 kDa 的多肽。

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来源期刊

Biology Bulletin 生物-生物学

CiteScore

0.70

自引率

20.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Biology Bulletin (Izvestiya Rossiiskoi Akademii Nauk – Seriya Biologicheskaya) is an interdisciplinary journal of general biology. It focuses on fundamental studies in the fields of cell biology, biochemistry, zoology, botany, physiology, and ecology. This journal publishes current materials of experimental studies and surveys on current problems in general biology. It also publishes information on scientific conferences and new books in the fields of general biology.