Three new C-27-carboxylated-lupane-triterpenoid derivatives from Potentilla discolor Bunge and their in vitro antitumor activities

Jing Zhang,Chao Liu,Hui-Feng Chen,Zhi-Xin Liao,Feng-Xiang Wang,Ri-Zhen Huang,Jin-Yue Sun,Xue-Kui Xia,Salvatore V Pizzo

doi:10.1371/journal.pone.0175502

Abstract

Three new lupane-triterpenoids (1–3) along with six known compounds (4–9) were isolated from the ethanolic extract of whole plant of Potentilla discolor Bunge. The structures of Compounds 1–3 were established by extensive 1D and 2D NMR together with other spectrum analysis, indicating that their C-27 positions were highly oxygenated, which were rarely found in nature. Their in vitro anti-proliferative activities against HepG-2, MCF-7 and T-84 cell lines were evaluated by Cell Counting Kit-8 (CCK-8) assay, and the results showed different activities for three cell lines with IC50 values ranging from 17.84 to 40.64 μM. In addition, the results from Hoechst 33258 and AO/EB staining as well as annexinV-FITC assays exhibited Compound 1 caused a markedly increased HepG-2 cellular apoptosis in a dose-dependent manner. The further mechanisms of Compound 1-induced cellular apoptosis were confirmed that 1 induced the production of ROS and the alteration of pro- and anti-apoptotic proteins, which led to the dysfunction of mitochondria and activation of caspase-9 and caspase-3 and finally caused cellular apoptosis. These results would be useful in search for new potential antitumor agents and for developing semisynthetic lupane-triterpenoid derivatives with high antitumor activity.

Highlights

Potentilla is one of a hundred genera in the family Rosaceae, subfamily Rosoideae, tribe Potentilleae [1, 2], which contains about 700 species
There are six methyl group signals at δ 0.82, 0.83, 0.89, 0.93, 1.04, 1.13 in the 1H NMR spectrum and 30 carbon signals in 13C NMR spectrum, which suggested that compound 1 was a triterpenoid [30]. δH 1.04 (d, 3H, J = 7.29) indicated that this methyl group coupled with a methine proton
Cytochrome c is reportedly involved in the activation of downstream caspases that trigger apoptosis, so these results indicated that caspases are involved in the apoptotic process downstream of mitochondria

Summary

Introduction

Potentilla is one of a hundred genera in the family Rosaceae, subfamily Rosoideae, tribe Potentilleae [1, 2], which contains about 700 species. They are widespread in temperate, arctic and Alpine zones of the Northern hemisphere. Potentilla species have been used in traditional medicine of different cultures by Asian, European and American for a long time [3,4,5,6,7,8]. Several pharmacopoeias include monographs on Potentilla species, e.g. European Pharmacopoeia 9.0, 2017 [9] and Chinese Pharmacopoeia 2015 [10].

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Results

Conclusion