Kouroshnia Arghavan, Zeinali Sirous, Irani Shiva, Sadeghi Akram
Department of Biology, Science and Research branch, Islamic Azad University, Tehran, Iran.
Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Cancer Cell Int. 2022 Jul 26;22(1):235. doi: 10.1186/s12935-022-02656-1.
Colorectal cancer is the third and most significant cause of death and fourth most common cancer in the world. Chemotherapy can be introduced in the cases of locally or distantly invasive colorectal cancer. In recent years Actinomycetes, especially the genus Streptomyces, contain numerous bioactive compounds, some of which are known as important anti-tumor chemotherapy drugs. In this research, we aimed to explore the anti-cancer mode of action of Streptomyces sp. 801 on colorectal cancer cells in vitro conditions.
Fermented supernatant of strain Streptomyces sp. 801 isolated from soil showed maximum growth inhibition on human colorectal cancer cells. The cytotoxic effects of various concentrations of EtOAc extract from bacterial culture supernatant on HT-29, HCT 116 and SW480 cancer cells were surveyed using the MTT assay. Moreover, flow cytometry assays and Bax, Bcl-2, Cyclin D1 and P21 gene expressions were carried out to assess the apoptotic and cell cycle effects. Also, the scratch assay was performed to measure migration. Finally, Ethyl acetate (EtOAc) extract was analyzed by LC-MS to identify anti-cancer compounds.
The cell viability of all three cell lines were decreased in a dose-dependent manner. The successful induction of apoptosis and cell cycle arrest at IC values, were confirmed by flow cytometry as well as by the mRNA expression levels of the genes involved in these processes. Scratch assays indicated the inhibition of cell migration in the cancer cell lines treated by Streptomyces sp. 801. Nine anti-cancer compounds of Streptomyces sp. 801 were detected by liquid chromatography-mass spectrometry (LC-MS) analysis.
These findings suggest that Streptomyces sp. 801 can be a source of promising anticancer metabolites.
结直肠癌是全球第三大致死原因且是第四大常见癌症。对于局部或远处侵袭性结直肠癌病例可采用化疗。近年来，放线菌，尤其是链霉菌属，含有众多生物活性化合物，其中一些是重要的抗肿瘤化疗药物。在本研究中，我们旨在探索链霉菌801在体外条件下对结直肠癌细胞的抗癌作用模式。
从土壤中分离出的链霉菌801菌株的发酵上清液对人结直肠癌细胞显示出最大生长抑制作用。使用MTT法检测细菌培养上清液中不同浓度乙酸乙酯提取物对HT - 29、HCT 116和SW480癌细胞的细胞毒性作用。此外，进行流式细胞术检测以及Bax、Bcl - 2、细胞周期蛋白D1和P21基因表达分析以评估凋亡和细胞周期效应。同时，进行划痕试验以测量细胞迁移。最后，通过液相色谱 - 质谱联用（LC - MS）分析乙酸乙酯（EtOAc）提取物以鉴定抗癌化合物。
所有三种细胞系的细胞活力均呈剂量依赖性降低。通过流式细胞术以及参与这些过程的基因的mRNA表达水平证实了在IC值下成功诱导凋亡和细胞周期停滞。划痕试验表明链霉菌801处理的癌细胞系中细胞迁移受到抑制。通过液相色谱 - 质谱联用（LC - MS）分析检测到链霉菌801的九种抗癌化合物。
这些发现表明链霉菌801可能是有前景的抗癌代谢物来源。
