Neothalfine, a potent natural anti-tumor agent against metastatic colorectal cancer and its primary mechanism

Bioorg Med Chem. 2021 Jan 1:29:115849. doi: 10.1016/j.bmc.2020.115849.

Yan-Yan Zhu ¹, Qiong Jin ², Shan-Shan Chen ¹, Dan-Ni Jin ¹, Zhao-Jie Wang ¹, Ying-Jie He ¹, Hui-Cheng Chen ¹, Yun-Li Zhao ¹, Li-Xing Zhao ¹, Zhi Dai ³, Xiao-Dong Luo ⁴

Affiliations

1 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, People's Republic of China.
2 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650201, People's Republic of China.
3 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, People's Republic of China. Electronic address: daizhi@ynu.edu.cn.
4 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, People's Republic of China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650201, People's Republic of China. Electronic address: xdluo@mail.kib.ac.cn.

PMID: 33221063 DOI: 10.1016/j.bmc.2020.115849

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.

Keywords

Bisbenzylisoquinoline alkaloid; Metabolomic; Metastatic colorectal cancer; Mitochondrial apoptosis; Neothalfine.

Name
Email *

	Sorry, but the email address you supplied was invalid.