1. Academic Validation
  2. Novel panaxadiol triazole derivatives induce apoptosis in HepG-2 cells through the mitochondrial pathway

Novel panaxadiol triazole derivatives induce apoptosis in HepG-2 cells through the mitochondrial pathway

  • Bioorg Chem. 2020 Sep;102:104078. doi: 10.1016/j.bioorg.2020.104078.
Shengnan Xiao 1 Xude Wang 1 Lei Xu 1 Tao Li 1 Jiaqing Cao 2 Yuqing Zhao 3
Affiliations

Affiliations

  • 1 School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 2 School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: jiaqingcao@163.com.
  • 3 School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China; Key Laboratory of Structure-based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: zyq4885@126.com.
Abstract

In this study, we introduced 1, 2, 4-triazole groups into panaxadiol (PD) to obtain 18 panaxadiol triazole derivatives. Five Cancer cells and one normal cell were evaluated for cytotoxicity by MTT assay. The results showed that most of the derivatives could inhibit Cancer cell proliferation, and the anti-proliferative activity of compound A1 was the most significant. For HepG-2 cells, the IC50 value was 4.21 ± 0.54 μM, which was nearly 15 times higher than the activity of PD. Further studies showed that compound A1 could induce Apoptosis in HepG-2 cells, and could enhance the expression of Cl-caspase-3, Cl-caspase-9 and Cl-PARP. Moreover, Western blot analysis showed that after treating HepG-2 cells with compound A1, the expression of p53 protein was increased and the ratio of Bax/Bcl-2 was gradually increased. The cytoplasmic Bax is then translocated to the mitochondria, causing the release of Cyt c protein. Therefore, the results indicate that compound A1 induces Apoptosis through the mitochondrial pathway and can be used the potential to develop new anti-proliferative agents.

Keywords

1, 2, 4-triazole; Anti-proliferative activity; Mitochondrial pathway; Panaxadiol; Synthesis.

Figures
Products