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.

Neothalfine 是一种天然的双苄基异喹啉生物碱，在药用植物中资源丰富，其抗肿瘤功效尚未见报道。在本研究中，研究了抗肿瘤功效，它对几种癌细胞系，尤其是转移性结直肠癌（HCT116、SW620、T84）显示出广谱活性，IC ₅₀值分别为 7.2、5.9、8.2 nM，大致等于众所周知的抗肿瘤剂多西紫杉醇（4.0、4.7、2.7 nM），是 CPT-11（4.4、5.1、6.9 μM）的近 1000 倍。此外，新沙芬通过导致细胞周期停滞在 G2/M 期来抑制结直肠细胞增殖，并通过线粒体功能障碍诱导细胞凋亡，通过非靶向代谢组学方法、线粒体膜电位和 caspase-3/7 活性测定触发内在凋亡途径。此外，neothalfine 在 3.5 nM 的浓度下显着破坏了结直肠癌克隆球的扩张，其功效是 CPT-11 (3.0 µM) 的近 1000 倍。结果支持新沙芬可能是进一步研究的抗肿瘤先导物。