α-松油醇作为临床前研究中的抗肿瘤候选药物。

Alpha-Terpineol as Antitumor Candidate in Pre-Clinical Studies.

机构信息

Toxicological Genetics Research Laboratory (LAPGENIC), Postgraduate Program in Pharmaceutical Sciences, Federal University of Piaui, Teresina, Piaui, Brazil.

Toxicological Genetics and Antitumor Evaluation Laboratory (TOXGEN), Senator Helvídio Nunes Campus of Barros-Picos-PI, Federal University of Piaui, Teresina, Piaui, Brazil.

出版信息

Anticancer Agents Med Chem. 2021;21(15):2023-2031. doi: 10.2174/1871520621999210104195820.

DOI:10.2174/1871520621999210104195820

PMID:33397274

Abstract

BACKGROUND

Alpha-terpineol is monoterpene alcohol with anti-tumor activity against different tumor cell lines (lung, breast, leukemias and colorectal) through blockage of NF-kB expression, which play an important role in tumor cells growth.

OBJECTIVE

Evaluate the antitumor activity of alpha-terpineol in murine Sarcoma 180 cell line.

METHODS

For the tests, different cytotoxic and genotoxic assays were used, including Trypan blue, cytokinesis- blocked micronucleus assay, comet assay, agarose gel DNA fragmentation, flow cytometry and cell viability using fluorescence. Ascitic fluid cells from sarcoma 180 were obtained from Mus musculus peritoneal cavity and Alpha-terpineol was tested at 100, 250 and 500 μg/mL. Doxorubicin and Cisplatin were used as positive controls.

RESULTS

Cytotoxic effects of alpha-terpineol were found in all concentrations tested, reducing cell viability in 50.9; 38.53; 30.82% at 100, 250 and 500 μg/mL, respectively. Alpha-terpineol induced genotoxic effects due to DNA fragmentation (increased frequency and index of damage), and was clastogenic by increased micronuclei formation, nucleoplasmic bridges and nuclear buds. DNA fragmentation and increased cell death indicated that alpha-terpineol can cause early, late, and necrotic apoptosis.

CONCLUSION

Our data indicate that alpha-terpineol has antitumor activity revealed by cytogenetic mechanisms and / or loss of cell membrane integrity.

摘要

背景

α-松油醇是一种单萜醇，通过阻断 NF-κB 的表达，对不同的肿瘤细胞系（肺癌、乳腺癌、白血病和结直肠癌）具有抗肿瘤活性，NF-κB 在肿瘤细胞生长中起着重要作用。

目的

评估α-松油醇在小鼠肉瘤 180 细胞系中的抗肿瘤活性。

方法

为了进行测试，使用了不同的细胞毒性和遗传毒性测定方法，包括台盼蓝法、胞质分裂阻断微核试验、彗星试验、琼脂糖凝胶 DNA 片段化、流式细胞术和荧光法检测细胞活力。从小鼠腹腔中获得肉瘤 180 的腹水细胞，并在 100、250 和 500μg/mL 下测试α-松油醇。阿霉素和顺铂用作阳性对照。

结果

在所有测试浓度下都发现了α-松油醇的细胞毒性作用，使细胞活力分别降低了 50.9%、38.53%和 30.82%。α-松油醇诱导 DNA 片段化（增加损伤的频率和指数）产生遗传毒性作用，并通过增加微核形成、核质桥和核芽导致染色体断裂。DNA 片段化和增加的细胞死亡表明，α-松油醇可以引起早期、晚期和坏死性细胞凋亡。