Bisdemethoxycurcumin attenuates gastric adenocarcinoma growth by inducing mitochondrial dysfunction

Luo,Changjiang; Du,Zhixing; Wei,Xing; Chen,Gang; Fu,Zhongxue

doi:10.3892/ol.2014.2685

Bisdemethoxycurcumin attenuates gastric adenocarcinoma growth by inducing mitochondrial dysfunction

Authors:
- Changjiang Luo
- Zhixing Du
- Xing Wei
- Gang Chen
- Zhongxue Fu
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Affiliations: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China, Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China, Department of Surgical ICU, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China
Published online on: November 7, 2014 https://doi.org/10.3892/ol.2014.2685
Pages: 270-274

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Abstract

Bisdemethoxycurcumin (BDMC) is a demethoxy derivative of curcumin. In this study, a human gastric adenocarcinoma xenograft model was generated in vivo using nude mice and BDMC was observed to suppress the growth and activity of tumors, in addition to improving the physical and mental capacity of the mice. An increased number of apoptotic cells, decreased ratio of B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein and increased caspase‑3 expression was also observed following treatment with BDMC, indicating that BDMC may promote apoptosis in tumors via mitochondrial modulation. The growth of SGC 7901 gastric cancer cells was inhibited and arrested at G1 phase. Specific indicators of mitochondrial dysfunction, a reduction in adenosine triphosphate generation, the inner mitochondrial membrane potential, augmentation of reactive oxygen species production and cytochrome c were also detected in the mitochondria following treatment with BDMC. These results indicate that BDMC attenuates gastric adenocarcinoma growth by inducing mitochondrial dysfunction.

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1	Hayashi Y, Blum MA and Ajani JA: Advanced gastroesophageal carcinoma: an update on the current therapeutic landscape. Onkologie. 35:204–209. 2012. View Article : Google Scholar : PubMed/NCBI
2	Esatbeyoglu T, Huebbe P, Ernst IM, Chin D, Wagner AE and Rimbach G: Curcumin - from molecule to biological function. Angew Chem Int Ed Engl. 51:5308–5332. 2012. View Article : Google Scholar : PubMed/NCBI
3	Zhang Y, Yao Y, Wang H, Guo Y, Zhang H and Chen L: Effects of salidroside on glioma formation and growth inhibition together with improvement of tumor microenvironment. Chin J Cancer Res. 25:520–526. 2013.PubMed/NCBI
4	Sheu MJ, Lin HY, Yang YH, Chou CJ, Chien YC, Wu TS and Wu CH: Demethoxycurcumin, a major active curcuminoid from Curcuma longa, suppresses balloon injury induced vascular smooth muscle cell migration and neointima formation: an in vitro and in vivo study. Mol Nutr Food Res. 57:1586–1597. 2013. View Article : Google Scholar : PubMed/NCBI
5	Kim DS, Kim JY and Han Y: Curcuminoids in neurodegenerative diseases. Recent Pat CNS Drug Discov. 7:184–204. 2012. View Article : Google Scholar : PubMed/NCBI
6	Chen MJ, Cheng YM, Lai PH, Wu JF and Hsu YC: In vitro biocompatibility of thermally gelling liquid mucoadhesive loaded curcuminoids in colorectal cancer chemoprevention. Int J Colorectal Dis. 27:869–878. 2012. View Article : Google Scholar : PubMed/NCBI
7	Ramadan G, Al-Kahtani MA and El-Sayed WM: Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber officinale (ginger) rhizomes in rat adjuvant-induced arthritis. Inflammation. 34:291–301. 2011. View Article : Google Scholar
8	Cidón EU: Gastric cancer and the search for a good prognostic classification: a challenge. Clin Exp Gastroenterol. 3:113–116. 2010. View Article : Google Scholar : PubMed/NCBI
9	Shamas-Din A, Kale J, Leber B and Andrews DW: Mechanisms of action of Bcl-2 family proteins. Cold Spring Harb Perspect Biol. 5:a0087142013. View Article : Google Scholar : PubMed/NCBI
10	Robertson JD and Orrenius S: Molecular mechanisms of apoptosis induced by cytotoxic chemicals. Crit Rev Toxicol. 30:609–627. 2000. View Article : Google Scholar : PubMed/NCBI
11	Garrido C, Galluzzi L, Brunet M, Puig PE, Didelot C and Kroemer G: Mechanisms of cytochrome c release from mitochondria. Cell Death Differ. 13:1423–1433. 2006. View Article : Google Scholar : PubMed/NCBI
12	Cain K: Chemical-induced apoptosis: formation of the Apaf-1 apoptosome. Drug Metab Rev. 35:337–363. 2003. View Article : Google Scholar
13	Gutierrez J, Ballinger SW, Darley-Usmar VM and Landar A: Free radicals, mitochondria, and oxidized lipids: the emerging role in signal transduction in vascular cells. Circ Res. 99:924–932. 2006. View Article : Google Scholar : PubMed/NCBI
14	Zhou F, Shen Q and Claret FX: Novel roles of reactive oxygen species in the pathogenesis of acute myeloid leukemia. J Leukoc Biol. 94:423–429. 2013. View Article : Google Scholar : PubMed/NCBI
15	Gasparre G, Porcelli AM, Lenaz G and Romeo G: Relevance of mitochondrial genetics and metabolism in cancer development. Cold Spring Harb Perspect Biol. 5:2013. View Article : Google Scholar : PubMed/NCBI
16	Smaili SS, Hsu YT, Carvalho AC, Rosenstoc TR, Sharpe JC and Youle RJ: Mitochondria, calcium and pro-apoptotic proteins as mediators in cell death signaling. Braz J Med Biol Res. 36:183–190. 2003. View Article : Google Scholar : PubMed/NCBI
17	Chazotte B: Labeling mitochondria with MitoTracker dyes. Cold Spring Harb Protoc. 9:990–992. 2011.
18	Marullo R, Werner E, Degtyareva N, Moore B, Altavilla G, Ramalingam SS and Doetsch PW: Cisplatin induces a mitochondrial-ROS response that contributes to cytotoxicity depending on mitochondrial redox status and bioenergetic functions. PLoS One. 8:e811622013. View Article : Google Scholar : PubMed/NCBI
19	Shimada K, Fujii T, Anai S, Fujimoto K and Konishi N: ROS generation via NOX4 and its utility in the cytological diagnosis of urothelial carcinoma of the urinary bladder. BMC Urol. 11:222011. View Article : Google Scholar : PubMed/NCBI
20	Yadav N and Chandra D: Mitochondrial and postmitochondrial survival signaling in cancer. Mitochondrion. 16:18–25. 2014. View Article : Google Scholar
21	Pérez-Payá E, Orzáez M, Mondragón L, Wolan D, Wells JA, Messeguer A and Vicent MJ: Molecules that modulate Apaf-1 activity. Med Res Rev. 31:649–675. 2011. View Article : Google Scholar