A triterpenoid saponin from Adenophora triphylla var. japonica suppresses the growth of human gastric cancer cells via regulation of apoptosis and autophagy

Abstract

In the present study, we investigated the effects of 3-O-β-D-galactopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucuronopyranosyl-28-O-[α-L-arabinopyranosyl-(1 → 4)-α-L-arabinopyranosyl-(1 → 3)-β-D-xylopyranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 2)-β-D-fucopyranosyl] quillaic acid, named compound 1, on the induction of apoptosis and autophagy in human gastric cancer AGS cells. Compound 1, a triterpenoid saponin isolated from the root of Adenophora triphylla var. japonica, effectively inhibited the growth of AGS cells by inducing apoptosis, as well as autophagy. Apoptosis by compound 1 treatment was associated with activation of caspases, release of cytochrome c, and increased ratio of Bax/Bcl-2. Autophagy by compound 1 treatment was indicated by LC3-II protein expression. We also found an increase in phosphorylation of p38 and JNK and a decrease in phosphorylation of ERK and Akt after compound 1 treatment. Furthermore, pretreatment with p38 inhibitor SB202190 completely inhibited compound 1-induced activation of caspases and cleavage of PARP1, whereas pretreatment with SB202190 synergistically increased the protein expression of LC3-II. These results suggest that compound 1 distinctly induces apoptotic and autophagic cell death and the increased autophagy by SB202190 protects compound 1-induced AGS cell death. Our findings provide an important clue for exploring the potential anticancer role of compound 1.

Ophiopogonin D′, a Natural Product From Radix Ophiopogonis, Induces in Vitro and in Vivo RIPK1-Dependent and Caspase-Independent Apoptotic Death in Androgen-Independent Human Prostate Cancer Cells

“…Because of their apparently safety and efficacy, triterpenoid saponins have been gaining increasing interest for cancer therapy ( Du et al, 2014 ; Singh et al, 2017 ). The anticancer triterpenoid saponins modulate numerous signaling targets related to angiogenesis, apoptosis, autophagy, cancer stem cells, inflammation, metastasis, microRNAs, multidrug resistance, proliferation, and oxidative stress ( Liu et al, 2013 ; Cheng et al, 2014 ; Chun et al, 2014 ; Du et al, 2014 ). Our previous studies have shown that Platycodin D (PD), another triterpenoid saponin, has potent activity against prostate ( Zhou et al, 2015 ) and breast/mammary gland ( Kong et al, 2016 ) cancers.…”

“…Natural products have provided an invaluable source of therapeutic agents, especially for anticancer drug discovery. Terpenoid saponins, including the triterpenoid saponins and diterpenoid saponins identified from many herbs, have been demonstrated to have activity against human cancer cells ( Haridas et al, 2001 ; Mujoo et al, 2001 ; Liu et al, 2013 ; Cheng et al, 2014 ; Chun et al, 2014 ; Du et al, 2014 ; Zhou et al, 2015 ; Singh et al, 2017 ). We recently examined four triterpenoid saponins and one diterpenoid saponin for their antitumor effects against androgen-independent PC3 prostate cancer cells.…”

Anticancer Effects of Sinocrassulosides VI/VII from Silene viscidula on HeLa Cells

“…The overexpression of p16 and the increased number of β -gal staining cells supported the evidence that sinocrassulosides VI/VII induced senescence in HeLa cells. Triterpenoid saponins have been proven as potential antitumor agents, due to their ability to induce apoptosis in cancer cells [27, 28]. We are the first to demonstrate that oleanane-type triterpenoid saponin from S. viscidula may inhibit cell proliferation by inducing cell cycle arrest and senescence besides the reported apoptosis mechanism.…”

Autophagy as a Therapeutic Target in Gastrointestinal Cancer

“…Therapeutic agents in gastrointestinal cancer are summarized in Tables 1 and 2 [46][47][48][49][50][51][52][53][54][55][56][57].…”