Crosstalk between mitochondrial ROS and depolarization in the potentiation of TRAIL-induced apoptosis in human tumor cells

Suzuki-Karasaki,Miki; Ochiai,Toyoko; Suzuki-Karasaki,Yoshihiro

doi:10.3892/ijo.2013.2215

Crosstalk between mitochondrial ROS and depolarization in the potentiation of TRAIL-induced apoptosis in human tumor cells

Authors:
- Miki Suzuki-Karasaki
- Toyoko Ochiai
- Yoshihiro Suzuki-Karasaki
View Affiliations

Affiliations: Department of Dermatology, Nihon University Surugadai Hospital, Tokyo 173-8610, Japan, Division of Physiology, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo 173-8610, Japan
Published online on: December 10, 2013 https://doi.org/10.3892/ijo.2013.2215
Pages: 616-628

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

We previously showed that membrane-depolarizing agents such as K+ and ATP-sensitive potassium (KATP) channel inhibitors potentiate tumor necrosis factor-related apoptosis‑inducing ligand (TRAIL)-induced apoptosis in human melanoma cells, but not in normal melanocytes. In this study, we investigated whether the tumor-selective effect of depolarization was observed among different tumor cell types and the mechanisms by which depolarization potentiates death pathways. We found that K+ and KATP channel inhibitors elicited similar apoptosis-potentiating effects in human tumor cells with different origins, including leukemia, melanoma and lung cancer cells. In contrast, minimal potentiation of apoptosis was observed in non-transformed lung cells. The potentiation was associated with increased mitochondrial and endoplasmic reticulum stress death pathways. Upregulation of surface TRAIL receptor-2 expression and modulation of the caspase-3 activation pathway seemed to play roles in the enhancement of death signaling. Moreover, the results showed that depolarization and mitochondria‑derived reactive oxygen species (mROS) mutually regulated one another. Depolarization potentiated TRAIL-induced mROS accumulation. Conversely, scavenging of mROS by the antioxidant MnTBaP reduced depolarization, whereas mROS accumulation caused by metabolic inhibitors potentiated the depolarization. These findings suggest a positive loop between depolarization and mROS accumulation. This may provide a rationale for the tumor-selective cytotoxicity and/or potentiation of TRAIL cytotoxicity of a wide variety of ROS-producing substances in different types of tumor cells.

View Figures

View References

1.	LeBlanc HN and Ashkenazi A: Apo2L/TRAIL and its death and decoy. Cell Death Differ. 10:66–75. 2003. View Article : Google Scholar : PubMed/NCBI
2.	Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ and Ashkenazi A: Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity. 12:612–620. 2000. View Article : Google Scholar : PubMed/NCBI
3.	Lavrik IN, Golks A and Krammer PH: Caspases: pharmacological manipulation of cell death. J Clin Invest. 15:2665–2662. 2005. View Article : Google Scholar
4.	Danial NN and Korsmeyer SJ: Cell death: critical control points. Cell. 116:205–219. 2014. View Article : Google Scholar
5.	Green DR: Apoptotic pathways: paper wraps stone blunts scissors. Cell. 102:1–4. 2000. View Article : Google Scholar : PubMed/NCBI
6.	Korsmeyer SJ, Wei MC, Saito M, Weiler S, Oh KJ and Schlesinger PH: Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death Differ. 7:1166–1173. 2000. View Article : Google Scholar : PubMed/NCBI
7.	Yan N and Shi Y: Mechanisms of apoptosis through structural biology. Annu Rev Cell Dev Biol. 21:35–56. 2005. View Article : Google Scholar : PubMed/NCBI
8.	Dyer MJ, MacFarlane M and Cohen GM: Barriers to effective TRAIL-targeted therapy of malignancy. J Clin Oncol. 25:4506–4507. 2007.PubMed/NCBI
9.	Bortner CD, Gomez-Angelats M and Cidlowski JA: Plasma membrane depolarization without repolarization is an early molecular event in anti-Fas-induced apoptosis. J Biol Chem. 276:4304–4314. 2001. View Article : Google Scholar : PubMed/NCBI
10.	Yin W, Li X, Feng S, et al: Plasma membrane depolarization and Na,K-ATPase impairment induced by mitochondrial toxins augment leukemia cell apoptosis via a novel mitochondrial amplification mechanism. Biochem Pharmacol. 78:191–202. 2009. View Article : Google Scholar
11.	Nolte F, Friedrich O, Rojewski M, Fink RH, Schrezenmeier H and Körper S: Depolarisation of the plasma membrane in the arsenic trioxide (As₂O₃)-and anti-CD95-induced apoptosis in myeloid cells. FEBS Lett. 578:85–89. 2004. View Article : Google Scholar : PubMed/NCBI
12.	Ghoumari AM, Piochon C, Tomkiewicz C, et al: Neuroprotective effect of mifepristone involves neuron depolarization. FASEB J. 20:1377–1386. 2006. View Article : Google Scholar : PubMed/NCBI
13.	Suzuki Y, Inoue T, Murai M, Suzuki-Karasaki M, Ochiai T and Ra C: Depolarization potentiates TRAIL-induced apoptosis in human melanoma cells: role for ATP-sensitive K⁺ channels and endoplasmic reticulum stress. Int J Oncol. 41:465–475. 2012.PubMed/NCBI
14.	Inoue T and Suzuki-Karasaki Y: Mitochondrial superoxide mediates mitochondrial and endoplasmic reticulum dysfunctions in TRAIL-induced apoptosis in Jurkat cells. Free Radic Biol Med. 61:273–284. 2013. View Article : Google Scholar : PubMed/NCBI
15.	Chen LH, Jiang CC, Kiejda KA, et al: Thapsigargin sensitizes human melanoma cells to TRAIL-induced apoptosis by up-regulation of TRAIL-R2 through the unfolded protein response. Carcinogenesis. 28:2328–2336. 2007. View Article : Google Scholar : PubMed/NCBI
16.	Jiang CC, Chen LH, Gillespie S, et al: Tunicamycin sensitizes human melanoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by up-regulation of TRAIL-R2 via the unfolded protein response. Cancer Res. 67:5880–5888. 2007. View Article : Google Scholar
17.	Liu H, Jiang CC, Lavis CJ, et al: 2-Deoxy-D-glucose enhances TRAIL-induced apoptosis in human melanoma cells through XBP-1-mediated up-regulation of TRAIL-R2. Mol Cancer. 8:1222009. View Article : Google Scholar : PubMed/NCBI
18.	Boyce M and Yuan J: Cellular response to endoplasmic reticulum stress: a matter of life or death. Cell Death Differ. 13:363–373. 2006. View Article : Google Scholar : PubMed/NCBI
19.	Breckenridge DG, Germain M, Mathai JP, Nguyen M and Shore GC: Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene. 22:8608–8618. 2003. View Article : Google Scholar : PubMed/NCBI
20.	Groenendyk J and Michalak M: Endoplasmic reticulum quality control and apoptosis. Acta Biochim Pol. 52:381–395. 2005.PubMed/NCBI
21.	Robinson KM, Janes MS, Pehar M, et al: Selective fluorescencet imaging of superoxide in vivo using ethidium-based probes. Proc Natl Acad Sci USA. 103:15038–15043. 2006. View Article : Google Scholar : PubMed/NCBI
22.	Mukhopadhyay P, Rajesh M, Kashiwaya Y, Haskó G and Pacher P: Simple quantitative detection of mitochondrial superoxide production in live cells. Biochem Biophys Res Commun. 358:203–208. 2007. View Article : Google Scholar : PubMed/NCBI
23.	Petit JM, Maftah A, Ratinaud MH and Julien R: 10N-nonyl acridine orange interacts with cardiolipin and allows the quantification of this phospholipid in isolated mitochondria. Eur J Biochem. 209:267–273. 1992. View Article : Google Scholar : PubMed/NCBI
24.	Griffith TS, Rauch CT, Smolak PJ, et al: Functional analysis of TRAIL receptors using monoclonal antibodies. J Immunol. 162:2597–2605. 1999.PubMed/NCBI
25.	Pukac L, Kanakaraj P, Humphreys R, et al: HGS-ETR1, a fully human TRAIL-receptor 1 monoclonal antibody, induces cell death in multiple tumour types in vitro and in vivo. Br J Cancer. 92:1430–1441. 2005. View Article : Google Scholar : PubMed/NCBI
26.	Georgakis GV, Li Y, Humphreys R, et al: Activity of selective fully human agonistic antibodies to the TRAIL death receptors TRAIL-R1 and TRAIL-R2 in primary and cultured lymphoma cells: induction of apoptosis and enhancement of doxorubicin- and bortezomib-induced cell death. Br J Haematol. 130:501–510. 2005. View Article : Google Scholar
27.	Tochigi M, Inoue T, Suzuki-Karasaki M, Ochiai T, Ra C and Suzuki-Karasaki Y: Hydrogen peroxide induces cell death in human TRAIL-resistant melanoma through intracellular superoxide generation. Int J Oncol. 42:863–872. 2013.PubMed/NCBI
28.	Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA and Yuan J: Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid beta. Nature. 403:98–103. 2000. View Article : Google Scholar : PubMed/NCBI
29.	Szegezdi E, Fitzgerald U and Samali A: Caspase-12 and ER-stress-mediated apoptosis: the story so far. Ann NY Acad Sci. 1010:186–194. 2003. View Article : Google Scholar : PubMed/NCBI
30.	Rutkowski DT and Kaufman RJ: A trip to the ER: coping with stress. Trends Cell Biol. 14:20–28. 2004. View Article : Google Scholar : PubMed/NCBI
31.	Jiang CC, Mao ZG, Avery-Kiejda KA, Wade M, Hersey P and Zhang XD: Glucose-regulated protein 78 antagonizes cisplatin and adriamycin in human melanoma cells. Carcinogenesis. 30:197–204. 2009. View Article : Google Scholar : PubMed/NCBI
32.	Mao ZG, Jiang CC, Yang F, Thorne RF, Hersey P and Zhang XD: TRAIL-induced apoptosis of human melanoma cells involves activation of caspase-4. Apoptosis. 15:1211–1222. 2010. View Article : Google Scholar : PubMed/NCBI
33.	Fas SC, Baumann S, Zhu JY, et al: Wogonin sensitizes resistant malignant cells to TNFalpha- and TRAIL-induced apoptosis. Blood. 108:3700–3706. 2006. View Article : Google Scholar : PubMed/NCBI
34.	Baumann S, Fas SC, Giaisi M, et al: Wogonin preferentially kills malignant lymphocytes and suppresses T-cell tumor growth by inducing PLCgamma1- and Ca²⁺-dependent apoptosis. Blood. 111:2354–2363. 2008. View Article : Google Scholar : PubMed/NCBI
35.	Powlny AA and Singh SV: Multitargeted prevention and therapy of cancer by diallyl trisulfide and related Allium vegetable-derived organosulfur compounds. Cancer Lett. 269:305–314. 2008. View Article : Google Scholar : PubMed/NCBI
36.	Murai M, Inoue T, Suzuki-Karasaki M, Ochiai T, Ra C, Nishida S, et al: Diallyl trisulfide sensitizes human melanoma cells to TRAIL-induced cell death by promoting endoplasmic reticulum-mediated apoptosis. Int J Oncol. 41:2029–2037. 2012.