1. Neothalfine, a potent natural anti-tumor agent against metastatic colorectal cancer and its primary mechanism
- Author
-
Yun-Li Zhao, Zhao-Jie Wang, Yan-Yan Zhu, Shan-Shan Chen, Ying-Jie He, Zhi Dai, Xiao-Dong Luo, Hui-Cheng Chen, Dan-Ni Jin, Li-Xing Zhao, and Qiong Jin
- Subjects
Colorectal cancer ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Mitochondrion ,01 natural sciences ,Biochemistry ,Structure-Activity Relationship ,Metabolomics ,Cell Line, Tumor ,Drug Discovery ,medicine ,Humans ,Molecular Biology ,Cell Proliferation ,Membrane Potential, Mitochondrial ,Membrane potential ,Biological Products ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Cell growth ,Mechanism (biology) ,Chemistry ,Organic Chemistry ,medicine.disease ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Docetaxel ,Apoptosis ,Cancer research ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Colorectal Neoplasms ,medicine.drug - Abstract
Neothalfine is a natural bisbenzylisoquinoline alkaloid with the abundant resource in medicinal plants and has not been reported its anti-tumor efficacy. In the present study, the anti-tumor efficacy was investigated and it showed broad-spectrum activity against several cancer cell lines, especially metastatic colorectal cancer (HCT116, SW620, T84) with the IC50 values of 7.2, 5.9, 8.2 nM, respectively, roughly equal to well-known anti-tumor agent docetaxel (4.0, 4.7, 2.7 nM) and nearly 1000 folds than CPT-11 (4.4, 5.1, 6.9 μM). Furthermore, neothalfine inhibited colorectal cell proliferation by resulting in cell cycle arrest at the G2/M phase and induced apoptosis through the dysfunction of mitochondria to trigger intrinsic apoptotic pathway by untargeted metabolomic method, mitochondrial membrane potential, and caspase-3/7 activity assay. Moreover, neothalfine damaged colorectal cancer clonal spheres expansion significantly at the concentration of 3.5 nM with nearly 1000 folds efficacy than CPT-11 (3.0 µM). The results supported that neothalfine might be an anti-tumor lead for further investigation.
- Published
- 2021