Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia.
Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia.
Molecules. 2021 Mar 12;26(6):1554. doi: 10.3390/molecules26061554.
This study reports on the cytotoxic properties of nordamnacanthal and damnacanthal, isolated from roots of on T-lymphoblastic leukaemia (CEM-SS) cell lines.
MTT assay, DNA fragmentation, ELISA and cell cycle analysis were carried out.
Nordamnacanthal and damnacanthal at IC values of 1.7 μg/mL and10 μg/mL, respectively. At the molecular level, these compounds caused internucleosomal DNA cleavage producing multiple 180-200 bp fragments that are visible as a "ladder" on the agarose gel. This was due to the activation of the Mg/Ca-dependent endonuclease. The induction of apoptosis by nordamnacanthal was different from the one induced by damnacanthal, in a way that it occurs independently of ongoing transcription process. Nevertheless, in both cases, the process of dephosphorylation of protein phosphates 1 and 2A, the ongoing protein synthesis and the elevations of the cytosolic Ca concentration were not needed for apoptosis to take place. Nordamnacanthal was found to have a cytotoxic effect by inducing apoptosis, while damnacanthal caused arrest at the G0/G1 phase of the cell cycle.
Damnacanthal and nordamnacanthal have anticancer properties, and could act as potential treatment for T-lymphoblastic leukemia.
本研究报告了从根中分离的 nordamnacanthal 和 damnacanthal 对 T 淋巴细胞白血病(CEM-SS)细胞系的细胞毒性特性。
进行了 MTT 测定、DNA 片段化、ELISA 和细胞周期分析。
Nordamnacanthal 和 damnacanthal 的 IC 值分别为 1.7 μg/mL 和 10 μg/mL。在分子水平上,这些化合物导致核小体间 DNA 断裂,产生多个 180-200 bp 的片段,在琼脂糖凝胶上可见为“梯状”。这是由于 Mg/Ca 依赖性内切酶的激活。Nordamnacanthal 诱导的细胞凋亡与 damnacanthal 诱导的细胞凋亡不同,它独立于正在进行的转录过程。然而,在这两种情况下,磷酸酶 1 和 2A 的去磷酸化、正在进行的蛋白质合成以及细胞溶质 Ca 浓度的升高都不需要发生细胞凋亡。Nordamnacanthal 通过诱导细胞凋亡具有细胞毒性作用,而 damnacanthal 导致细胞周期停留在 G0/G1 期。
Damnacanthal 和 nordamnacanthal 具有抗癌特性,可作为治疗 T 淋巴细胞白血病的潜在药物。