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

Chen,Xi; Yuan,Lin-Qing; Li,Lin-Jie; Lv,Yao; Chen,Pei-Feng; Pan,Lei

doi:10.3892/or.2017.5747

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

Authors:
- Xi Chen
- Lin-Qing Yuan
- Lin-Jie Li
- Yao Lv
- Pei-Feng Chen
- Lei Pan
View Affiliations

Affiliations: Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, P.R. China
Published online on: June 22, 2017 https://doi.org/10.3892/or.2017.5747
Pages: 1051-1058

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	Safarzadeh E, Shotorbani Sandoghchian S and Baradaran B: Herbal medicine as inducers of apoptosis in cancer treatment. Adv Pharm Bull. 4:(Suppl 1). 421–427. 2014.PubMed/NCBI
2	Srivastava S, Somasagara RR, Hegde M, Nishana M, Tadi SK, Srivastava M, Choudhary B and Raghavan SC: Quercetin, a natural flavonoid interacts with DNA, arrests cell cycle and causes tumor regression by activating mitochondrial pathway of apoptosis. Sci Rep. 6:240492016. View Article : Google Scholar : PubMed/NCBI
3	Jiang K, Wang W, Jin X, Wang Z, Ji Z and Meng G: Silibinin, a natural flavonoid, induces autophagy via ROS-dependent mitochondrial dysfunction and loss of ATP involving BNIP3 in human MCF7 breast cancer cells. Oncol Rep. 33:2711–2718. 2015.PubMed/NCBI
4	Kumar G, Mittal S, Sak K and Tuli HS: Molecular mechanisms underlying chemopreventive potential of curcumin: Current challenges and future perspectives. Life Sci. 148:313–328. 2016. View Article : Google Scholar : PubMed/NCBI
5	Jin P, Zhang C and Li N: Berberine exhibits antitumor effects in human ovarian cancer cells. Anticancer Agents Med Chem. 15:511–516. 2015. View Article : Google Scholar : PubMed/NCBI
6	Fang LH, Wang RP, Hu SY, Teng YH and Xie WB: The effect of tou nong san on transplanted tumor growth in nude mice. Evid Based Complement Alternat Med. 2015:5184542015. View Article : Google Scholar : PubMed/NCBI
7	Chua M, Baldwin TC, Hocking TJ and Chan K: Traditional uses and potential health benefits of Amorphophallus konjac K. Koch ex N.E.Br. J Ethnopharmacol. 128:268–278. 2010. View Article : Google Scholar : PubMed/NCBI
8	Committee CP: Pharmacopoeia of the People's Republic of China. 1st. Beijing: China Chemical Industry Press; 2010
9	Luo DY: Inhibitory effect of refined Amorphophallus konjac on MNNG-induced lung cancers in mice. Zhonghua Zhong Liu Za Zhi. 14:48–50. 1992.(In Chinese). PubMed/NCBI
10	Ansil PN, Nitha A, Prabha SP and Latha MS: Curative effect of Amorphophallus campanulatus (Roxb.) Blume. tuber on N-nitrosodiethylamine-induced hepatocellular carcinoma in rats. J Environ Pathol Toxicol Oncol. 33:205–218. 2014. View Article : Google Scholar : PubMed/NCBI
11	Ansil PN, Wills PJ, Varun R and Latha MS: Cytotoxic and apoptotic activities of Amorphophallus campanulatus tuber extracts against human hepatoma cell line. Res Pharm Sci. 9:269–277. 2014.PubMed/NCBI
12	Ansil PN, Prabha SP, Nitha A and Latha MS: Chemopreventive effect of Amorphophallus campanulatus (Roxb.) blume tuber against aberrant crypt foci and cell proliferation in 1, 2-dimethylhydrazine induced colon carcinogenesis. Asian Pac J Cancer Prev. 14:5331–5339. 2013. View Article : Google Scholar : PubMed/NCBI
13	Mariño G, Niso-Santano M, Baehrecke EH and Kroemer G: Self-consumption: The interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol. 15:81–94. 2014. View Article : Google Scholar : PubMed/NCBI
14	Booth LA, Tavallai S, Hamed HA, Cruickshanks N and Dent P: The role of cell signalling in the crosstalk between autophagy and apoptosis. Cell Signal. 26:549–555. 2014. View Article : Google Scholar : PubMed/NCBI
15	White E: Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer. 12:401–410. 2012. View Article : Google Scholar : PubMed/NCBI
16	Li T, Tang ZH, Xu WS, Wu GS, Wang YF, Chang LL, Zhu H, Chen XP, Wang YT, Chen Y, et al: Platycodin D triggers autophagy through activation of extracellular signal-regulated kinase in hepatocellular carcinoma HepG2 cells. Eur J Pharmacol. 749:81–88. 2015. View Article : Google Scholar : PubMed/NCBI
17	Chen LL, Song JX, Lu JH, Yuan ZW, Liu LF, Durairajan SS and Li M: Corynoxine, a natural autophagy enhancer, promotes the clearance of alpha-synuclein via Akt/mTOR pathway. J Neuroimmune Pharmacol. 9:380–387. 2014. View Article : Google Scholar : PubMed/NCBI
18	Xu D, Lao Y, Xu N, Hu H, Fu W, Tan H, Gu Y, Song Z, Cao P and Xu H: Identification and characterization of anticancer compounds targeting apoptosis and autophagy from Chinese native Garcinia species. Planta Med. 81:79–89. 2015.PubMed/NCBI
19	Chen PF and Liu LM: Observation on the anti-tumor effects and induction carcinoma cell's apoptosis of She Liu Gu. Chinese J Bas Med TCM. 6:30–32. 2000.(In Chinese).
20	Pan L and Chen PF: In vitro and in vivo suppression of hepatocellular carcinoma by amorphophallus konjac tuber through regulation of survivin and bax. Oncol Lett. (In press).
21	Maiuri MC, Zalckvar E, Kimchi A and Kroemer G: Self-eating and self-killing: Crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 8:741–752. 2007. View Article : Google Scholar : PubMed/NCBI
22	Li B, Xia J, Wang Y and Xie B: Grain-size effect on the structure and antiobesity activity of konjac flour. J Agric Food Chem. 53:7404–7407. 2005. View Article : Google Scholar : PubMed/NCBI
23	Fan YJ and Zong WX: The cellular decision between apoptosis and autophagy. Chin J Cancer. 32:121–129. 2013.PubMed/NCBI
24	Rubinstein AD and Kimchi A: Life in the balance - a mechanistic view of the crosstalk between autophagy and apoptosis. J Cell Sci. 125:5259–5268. 2012. View Article : Google Scholar : PubMed/NCBI
25	Zalewski BM, Chmielewska A and Szajewska H: The effect of glucomannan on body weight in overweight or obese children and adults: A systematic review of randomized controlled trials. Nutrition. 31:437–442e432. 2015. View Article : Google Scholar : PubMed/NCBI
26	Zalewski BM and Szajewska H: Effect of glucomannan supplementation on body weight in overweight and obese children: Protocol of a randomised controlled trial. BMJ Open. 5:e0072442015. View Article : Google Scholar : PubMed/NCBI
27	Harmayani E, Aprilia V and Marsono Y: Characterization of glucomannan from Amorphophallus oncophyllus and its prebiotic activity in vivo. Carbohydr Polym. 112:475–479. 2014. View Article : Google Scholar : PubMed/NCBI
28	XH K: Chemistry of Chinese Materia Medica. China Press of Traditional Chinese Medicine Beijing: 2003
29	Li JHX: Study on Chemical Components of Petroleum Ether Fraction of Alcohol Extract Obtained from Amorphophallus Blume. J Xihua University-Natural Sci. 28:68–69. 2009.
30	Jy Y: The cultivation and application of Amorphophallus Konjac. Hangzhou: Hangzhou University Press; 1991
31	Wang P, Chen Z, Meng ZQ, Luo JM, Lin JH, Zhou ZH, Chen H, Wang K, Shen YH and Liu LM: Ski acts as therapeutic target of qingyihuaji formula in the treatment of SW1990 pancreatic cancer. Integr Cancer Ther. 9:50–58. 2010. View Article : Google Scholar : PubMed/NCBI
32	Xu Y, Zhu F, Xu S and Liu L: Anti-tumor effect of the extract from qingyihuaji formula on pancreatic cancer by down-regulating Notch-4 and Jagged-1. J Tradit Chin Med. 35:77–83. 2015. View Article : Google Scholar : PubMed/NCBI
33	Altieri DC: Validating survivin as a cancer therapeutic target. Nat Rev Cancer. 3:46–54. 2003. View Article : Google Scholar : PubMed/NCBI
34	Sah NK, Khan Z, Khan GJ and Bisen PS: Structural, functional and therapeutic biology of survivin. Cancer Lett. 244:164–171. 2006. View Article : Google Scholar : PubMed/NCBI
35	Altieri DC: Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer. 8:61–70. 2008. View Article : Google Scholar : PubMed/NCBI
36	Chao DT and Korsmeyer SJ: BCL-2 family: Regulators of cell death. Annu Rev Immunol. 16:395–419. 1998. View Article : Google Scholar : PubMed/NCBI
37	Mizushima N, Yoshimori T and Levine B: Methods in mammalian autophagy research. Cell. 140:313–326. 2010. View Article : Google Scholar : PubMed/NCBI
38	Komatsu M, Waguri S, Ueno T, Iwata J, Murata S, Tanida I, Ezaki J, Mizushima N, Ohsumi Y, Uchiyama Y, et al: Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol. 169:425–434. 2005. View Article : Google Scholar : PubMed/NCBI
39	Nakatogawa H: Two ubiquitin-like conjugation systems that mediate membrane formation during autophagy. Essays Biochem. 55:39–50. 2013. View Article : Google Scholar : PubMed/NCBI
40	Liu LWL and Lin S: Therapeutic evaluation on advanced pancreatic cancer treated by integrative Chinese and western medicine: Clinical analysis of 56 cases. Chin J Integr Med. 10:236–237. 2004. View Article : Google Scholar