Suppression of gastric cancer by extract from the tuber of amorphophallus konjac via induction of apoptosis and autophagy

Abstract

The tuber of amorphophallus konjac (TuAK) is an antitumor herb used in traditional Chinese medicine. The present study investigated the inhibitory effect of TuAK against gastric cancer and the underlying mechanisms associated with two programmed cell death pathways, apoptosis and autophagy. TuAK was extracted by organic solvents including ethanol and ligarine. The extract of TuAK, shortened as TuAKe, significantly inhibited the growth of cultured gastric cancer cell lines SGC-7901 and AGS, with IC50 of 35-45 µg/ml. TuAKe could increase cell apoptosis and induce cell cycle arrest. For the apoptosis-associated proteins, expressions of survivin and Bcl-2 were decreased by treatment of TuAKe, and the expression of Bax and caspase-9 was increased. Furthermore, TuAKe could promote autophagy, and the antitumor efficacy of TuAKe was significantly hampered by targeted suppression of autophagy, suggesting that autophagy contributed to TuAKe-induced cell death. Furthermore, patients with gastric cancer who received TuAK-based medicinal decoction achieved improved scores in assessment of life quality compared with those without TuAK treatment. This study demonstrated the antitumor activity of TuAKe against gastric cancer, and is the first report to show that the underlying mechanism is associated with induction of autophagy. Our data provided support of the clinical use of amorphophallus konjac-based medication in combination with classical chemotherapy to achieve optimized outcome for gastric cancer.

Active fraction of clove induces apoptosis via PI3K/Akt/mTOR-mediated autophagy in human colorectal cancer HCT-116 cells

“…Therefore, inducing autophagy-associated cell death of cancer cells may be useful in cancer treatment (49)(50)(51)(52). An extract from the tuber of Amorphaphallus was reported to suppress the growth of proliferation of SGC-7901 and AGS cancer cells by induction of apoptosis and autophagy (53). Fenugreek extract also displayed anticancer effects through induction of autophagy and autophagy-associated death in human T lymphoma jurkat cells (54).…”

A Systematic Review Exploring the Anticancer Activity and Mechanisms of Glucomannan

“…Nowadays, it mainly serves either as a dietary supplement aiding in weight loss, diabetes, arterial sclerosis, and constipation, or as an emulsifier and thickener in food processing (Chen et al, 2017a; Wu et al, 2018), which corroborates the old theory of “homology of medicine and food.” In fact, many natural polysaccharides that show potent anti-tumor activity (Kim et al, 2011; Xiao et al, 2017; Zhang, 2017; Deng et al, 2018) derive from edible herbs, such as Lentinus , Cordyceps , Ganoderma lucidum , and Hericium , which themselves are also common cuisine ingredients. Recently, glucomannan extracted from Amorphophallus konjac (Chen et al, 2017a), Bletilla striata (Zhan et al, 2014), Lentinus edodes (Fujii et al, 1978), Aloe vera (Sampedro et al, 2004; Im et al, 2005; Liu et al, 2006; Im et al, 2016; Quezada et al, 2017), and Candida utilis (Kumano et al, 1985) were demonstrated to have similar effect. Moreover, according to the studies reviewed in the present research, glucomannan, mainly from these species, not only is an anti-cancer drug by itself but also works as a targeted carrier that is compatible with various bioactive compounds.…”

“…Given that tumor cells are apoptosis resistant, drugs aimed to promote apoptosis are widely used in cancer therapy (Hassan et al, 2014). Initially, studies unveiled the therapeutic effect of extract from A. konjac (AKe) on various cancers, such as colon carcinoma (Ansil et al, 2013; Ansil et al, 2014a), gastric cancer (Chen et al, 2017a), hepatoma (Ansil et al, 2014b), and breast cancer (Wu et al, 2018; Wu et al, 2019). Chen et al found that AKe could inhibit the growth of in vitro cultured gastric cancer cell lines SGC-7901 and AGS (Chen et al, 2017a).…”

“…Initially, studies unveiled the therapeutic effect of extract from A. konjac (AKe) on various cancers, such as colon carcinoma (Ansil et al, 2013; Ansil et al, 2014a), gastric cancer (Chen et al, 2017a), hepatoma (Ansil et al, 2014b), and breast cancer (Wu et al, 2018; Wu et al, 2019). Chen et al found that AKe could inhibit the growth of in vitro cultured gastric cancer cell lines SGC-7901 and AGS (Chen et al, 2017a). On the molecular level, the expression of inhibitors of apoptosis protein (IAP) family member survivin and the pro-survival gene BCL2 decreased, while the pro-apoptosis protein BAX and caspase-9 increased (Chen et al, 2017a) ( Figure 1 ).…”

“…Chen et al found that AKe could inhibit the growth of in vitro cultured gastric cancer cell lines SGC-7901 and AGS (Chen et al, 2017a). On the molecular level, the expression of inhibitors of apoptosis protein (IAP) family member survivin and the pro-survival gene BCL2 decreased, while the pro-apoptosis protein BAX and caspase-9 increased (Chen et al, 2017a) ( Figure 1 ). AKe also displayed similar therapeutic effect on human liver cancer cell line and the human triple-negative breast cancer (TNBC) cells (Ansil et al, 2014b; Wu et al, 2018).…”