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BMC Cancer
Published in: BMC Cancer 1/2010

Open Access 01-12-2010 | Research article

1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes induce autophagic cell death in estrogen receptor negative breast cancer

Authors: Kathy Vanderlaag, Yunpeng Su, Arthur E Frankel, Robert C Burghardt, Rola Barhoumi, Gayathri Chadalapaka, Indira Jutooru, Stephen Safe

Published in: BMC Cancer | Issue 1/2010

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Abstract

Background

A novel series of methylene-substituted DIMs (C-DIMs), namely 1,1-bis(3'-indolyl)-1-(p-substituted phenyl)methanes containing t-butyl (DIM-C-pPhtBu) and phenyl (DIM-C-pPhC6H5) groups inhibit proliferation of invasive estrogen receptor-negative MDA-MB-231 and MDA-MB-453 human breast cancer cell lines with IC50 values between 1-5 uM. The main purpose of this study was to investigate the pathways of C-DIM-induced cell death.

Methods

The effects of the C-DIMs on apoptotic, necrotic and autophagic cell death were determined using caspase inhibitors, measurement of lactate dehydrogenase release, and several markers of autophagy including Beclin and light chain associated protein 3 expression (LC3).

Results

The C-DIM compounds did not induce apoptosis and only DIM-C-pPhCF3 exhibited necrotic effects. However, treatment of MDA-MB-231 and MDA-MB-453 cells with C-DIMs resulted in accumulation of LC3-II compared to LC3-I protein, a characteristic marker of autophagy, and transient transfection of green fluorescent protein-LC3 also revealed that treatment with C-DIMs induced a redistribution of LC3 to autophagosomes after C-DIM treatment. In addition, the autofluorescent drug monodansylcadaverine (MDC), a specific autophagolysosome marker, accumulated in vacuoles after C-DIM treatment, and western blot analysis of lysates from cells treated with C-DIMs showed that the Beclin 1/Bcl-2 protein ratio increased.

Conclusion

The results suggest that C-DIM compounds may represent a new mechanism-based agent for treating drug-resistant ER-negative breast tumors through induction of autophagy.
Appendix
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Literature
1.
Bradlow HL, Michnovicz JJ, Telang NT, Osborne MP: Effects of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice. Carcinogenesis. 1991, 12: 1571-1574. 10.1093/carcin/12.9.1571.CrossRefPubMed
2.
Chen I, McDougal A, Wang F, Safe S: Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. Carcinogenesis. 1998, 19: 1631-1639. 10.1093/carcin/19.9.1631.CrossRefPubMed
3.
Chinni SR, Li Y, Upadhyay S, Koppolu PK, Sarkar FH: Indole-3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells. Oncogene. 2001, 20: 2927-2936. 10.1038/sj.onc.1204365.CrossRefPubMed
4.
Grubbs CJ, Steele VE, Casebolt T, Juliana MM, Eto I, Whitaker LM, Dragnev KH, Kelloff GJ, Lubet RL: Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol. Anticancer Res. 1995, 15: 709-716.PubMed
5.
Hong C, Kim HA, Firestone GL, Bjeldanes LF: 3,3'-Diindolylmethane (DIM) induces a G1 cell cycle arrest in human breast cancer cells that is accompanied by Sp1-mediated activation of p21WAF1/CIP1 expression. Carcinogenesis. 2002, 23: 1297-1305. 10.1093/carcin/23.8.1297.CrossRefPubMed
6.
Tanaka T, Kojima T, Morishita Y, Mori H: Inhibitory effects of the natural products indole-3-carbinol and sinigrin during initiation and promotion phases of 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis. Jpn J Cancer Res. 1992, 83: 835-842.CrossRefPubMed
7.
Cohen JH, Kristal AR, Stanford JL: Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst. 2000, 92: 61-81. 10.1093/jnci/92.1.61.CrossRefPubMed
8.
Kolonel LN, Hankin JH, Whittemore AS, Wu AH, Gallagher RP, Wilkens LR, John EM, Howe GR, Dreon DM, West DW, et al: Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study. Cancer Epidemiol Biomarkers Prev. 2000, 9: 795-804.PubMed
9.
Kristal AR, Lampe JW: Brassica vegetables and prostate cancer risk: a review of the epidemiological evidence. Nutr Cancer. 2002, 42: 1-9. 10.1207/S15327914NC421_1.CrossRefPubMed
10.
Murillo G, Mehta RG: Cruciferous vegetables and cancer prevention. Nutr Cancer. 2001, 41: 17-28. 10.1207/S15327914NC41-1&2_2.CrossRefPubMed
11.
Zhang SM, Hunter DJ, Rosner BA, Giovannucci EL, Colditz GA, Speizer FE, Willett WC: Intakes of fruits, vegetables, and related nutrients and the risk of non-Hodgkin's lymphoma among women. Cancer Epidemiol Biomarkers Prev. 2000, 9: 477-485.PubMed
12.
Vanderlaag K, Samudio I, Burghardt R, Barhoumi R, Safe S: Inhibition of breast cancer cell growth and induction of cell death by 1,1-bis(3'-indolyl)methane (DIM) and 5,5'-dibromoDIM. Cancer Lett. 2005, 236: 198-212. 10.1016/j.canlet.2005.05.036.CrossRefPubMed
13.
Abdelrahim M, Newman K, Vanderlaag K, Samudio I, Safe S: 3,3'-Diindolylmethane (DIM) and derivatives induce apoptosis in pancreatic cancer cells through endoplasmic reticulum stress-dependent upregulation of DR5. Carcinogenesis. 2006, 27: 717-728. 10.1093/carcin/bgi270.CrossRefPubMed
14.
Bhuiyan MM, Li Y, Banerjee S, Ahmed F, Wang Z, Ali S, Sarkar FH: Down-regulation of androgen receptor by 3,3'-diindolylmethane contributes to inhibition of cell proliferation and induction of apoptosis in both hormone-sensitive LNCaP and insensitive C4-2B prostate cancer cells. Cancer Res. 2006, 66: 10064-10072. 10.1158/0008-5472.CAN-06-2011.CrossRefPubMed
15.
Rahman KW, Li Y, Wang Z, Sarkar SH, Sarkar FH: Gene expression profiling revealed survivin as a target of 3,3'-diindolylmethane-induced cell growth inhibition and apoptosis in breast cancer cells. Cancer Res. 2006, 66: 4952-4960. 10.1158/0008-5472.CAN-05-3918.CrossRefPubMed
16.
Kim EJ, Park SY, Shin HK, Kwon DY, Surh YJ, Park JH: Activation of caspase-8 contributes to 3,3'-Diindolylmethane-induced apoptosis in colon cancer cells. J Nutr. 2007, 137: 31-36.PubMed
17.
Hong C, Firestone GL, Bjeldanes LF: Bcl-2 family-mediated apoptotic effects of 3,3'-diindolylmethane (DIM) in human breast cancer cells. Biochem Pharmacol. 2002, 63: 1085-1097. 10.1016/S0006-2952(02)00856-0.CrossRefPubMed
18.
Cover CM, Hsieh SJ, Tran SH, Hallden G, Kim GS, Bjeldanes LF, Firestone GL: Indole-3-carbinol inhibits the expression of cyclin-dependent kinase-6 and induces a G1 cell cycle arrest of human breast cancer cells independent of estrogen receptor signaling. J Biol Chem. 1998, 273: 3838-3847. 10.1074/jbc.273.7.3838.CrossRefPubMed
19.
Chintharlapalli S, Papineni S, Safe S: 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes inhibit colon cancer cell and tumor growth through PPARγ-dependent and PPARγ-independent pathways. Mol Cancer Ther. 2006, 5: 1362-1370. 10.1158/1535-7163.MCT-06-0002.CrossRefPubMed
20.
Lei P, Abdelrahim M, Safe S: 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes inhibit ovarian cancer cell growth through peroxisome proliferator-activated receptor-dependent and independent pathways. Mol Cancer Ther. 2006, 5: 2324-2336. 10.1158/1535-7163.MCT-06-0184.CrossRefPubMed
21.
Hong J, Samudio I, Liu S, Abdelrahim M, Safe S: Peroxisome proliferator-activated receptor γ-dependent activation of p21 in Panc-28 pancreatic cancer cells involves Sp1 and Sp4 proteins. Endocrinology. 2004, 145: 5774-5785. 10.1210/en.2004-0686.CrossRefPubMed
22.
Chintharlapalli S, Smith R, Samudio I, Zhang W, Safe S: 1,1-Bis(3'-indolyl)-1-(p-substitutedphenyl)methanes induce peroxisome proliferator-activated receptor γ-mediated growth inhibition, transactivation and differentiation markers in colon cancer cells. Cancer Res. 2004, 64: 5994-6001. 10.1158/0008-5472.CAN-04-0399.CrossRefPubMed
23.
Chintharlapalli S, Burghardt R, Papineni S, Ramaiah S, Yoon K, Safe S: Activation of Nur77 by selected 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes induces apoptosis through nuclear pathways. J Biol Chem. 2005, 280: 24903-24914. 10.1074/jbc.M500107200.CrossRefPubMed
24.
Kassouf W, Chintharlapalli S, Abdelrahim M, Nelkin G, Safe S, Kamat AM: Inhibition of bladder tumor growth by 1,1-bis(3'-indolyl)-1-(p-substitutedphenyl)methanes: a new class of peroxisome proliferator-activated receptor γ agonists. Cancer Res. 2006, 66: 412-418. 10.1158/0008-5472.CAN-05-2755.CrossRefPubMed
25.
Qin C, Morrow D, Stewart J, Spencer K, Porter W, Smith R, Phillips T, Abdelrahim M, Samudio I, Safe S: A new class of peroxisome proliferator-activated receptor γ (PPARγ) agonists that inhibit growth of breast cancer cells: 1,1-bis(3'-indolyl)-1-(p-substitutedphenyl)methanes. Mol Cancer Therap. 2004, 3: 247-259.
26.
Vanderlaag K, Su Y, Frankel AE, Grage H, Smith R, Khan S, Safe S: 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes inhibit proliferation of estrogen receptor-negative breast cancer cells by activation of multiple pathways. Breast Cancer Res Treat. 2008, 109: 273-283. 10.1007/s10549-007-9648-y.CrossRefPubMed
27.
Biederbick A, Kern HF, Elsasser HP: Monodansylcadaverine (MDC) is a specific in vivo marker for autophagic vacuoles. Eur J Cell Biol. 1995, 66: 3-14.PubMed
28.
Herman-Antosiewicz A, Johnson DE, Singh SV: Sulforaphane causes autophagy to inhibit release of cytochrome C and apoptosis in human prostate cancer cells. Cancer Res. 2006, 66: 5828-5835. 10.1158/0008-5472.CAN-06-0139.CrossRefPubMed
29.
Gorka M, Daniewski WM, Gajkowska B, Lusakowska E, Godlewski MM, Motyl T: Autophagy is the dominant type of programmed cell death in breast cancer MCF-7 cells exposed to AGS 115 and EFDAC, new sesquiterpene analogs of paclitaxel. Anticancer Drugs. 2005, 16: 777-788. 10.1097/01.cad.0000171514.50310.85.CrossRefPubMed
30.
Kanzawa T, Kondo Y, Ito H, Kondo S, Germano I: Induction of autophagic cell death in malignant glioma cells by arsenic trioxide. Cancer Res. 2003, 63: 2103-2108.PubMed
31.
Kanzawa T, Germano IM, Komata T, Ito H, Kondo Y, Kondo S: Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ. 2004, 11: 448-457. 10.1038/sj.cdd.4401359.CrossRefPubMed
32.
Bursch W, Ellinger A, Kienzl H, Torok L, Pandey S, Sikorska M, Walker R, Hermann RS: Active cell death induced by the anti-estrogens tamoxifen and ICI 164 384 in human mammary carcinoma cells (MCF-7) in culture: the role of autophagy. Carcinogenesis. 1996, 17: 1595-1607. 10.1093/carcin/17.8.1595.CrossRefPubMed
33.
Paglin S, Hollister T, Delohery T, Hackett N, McMahill M, Sphicas E, Domingo D, Yahalom J: A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res. 2001, 61: 439-444.PubMed
34.
Butler R, Mitchell SH, Tindall DJ, Young CY: Nonapoptotic cell death associated with S-phase arrest of prostate cancer cells via the peroxisome proliferator-activated receptor gamma ligand, 15-deoxy-Δ(12,14)-prostaglandin J2. Cell Growth Differ. 2000, 11: 49-61.PubMed
35.
Kuo PL, Hsu YL, Cho CY: Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian target of rapamycin pathway in breast cancer cells. Mol Cancer Ther. 2006, 5: 3209-3221. 10.1158/1535-7163.MCT-06-0478.CrossRefPubMed
36.
Chen Y, Yang L, Feng C, Wen LP: Nano neodymium oxide induces massive vacuolization and autophagic cell death in non-small cell lung cancer NCI-H460 cells. Biochem Biophys Res Commun. 2005, 337: 52-60. 10.1016/j.bbrc.2005.09.018.CrossRefPubMed
37.
Hoyer-Hansen M, Bastholm L, Mathiasen IS, Elling F, Jaattela M: Vitamin D analog EB1089 triggers dramatic lysosomal changes and Beclin 1-mediated autophagic cell death. Cell Death Differ. 2005, 12: 1297-1309. 10.1038/sj.cdd.4401651.CrossRefPubMed
38.
Shao Y, Gao Z, Marks PA, Jiang X: Apoptotic and autophagic cell death induced by histone deacetylase inhibitors. Proc Natl Acad Sci USA. 2004, 101: 18030-18035. 10.1073/pnas.0408345102.CrossRefPubMedPubMedCentral
39.
Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T: LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000, 19: 5720-5728. 10.1093/emboj/19.21.5720.CrossRefPubMedPubMedCentral
40.
Yamamoto A, Tagawa Y, Yoshimori T, Moriyama Y, Masaki R, Tashiro Y: Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells. Cell Struct Funct. 1998, 23: 33-42. 10.1247/csf.23.33.CrossRefPubMed
41.
Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson CB, Tsujimoto Y: Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol. 2004, 6: 1221-1228. 10.1038/ncb1192.CrossRefPubMed
42.
Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, Packer M, Schneider MD, Levine B: Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 2005, 122: 927-939. 10.1016/j.cell.2005.07.002.CrossRefPubMed
43.
Mueller E, Sarraf P, Tontonoz P, Martin KJ, Zhang M, Fletcher C, Singer S, Spiegelman BM: Terminal differentiation of human breast cancer through PPARγ. Mol Cell. 1998, 1: 465-470. 10.1016/S1097-2765(00)80047-7.CrossRefPubMed
44.
Elstner E, Muller C, Koshizuka K, Williamson EA, Park D, Asou H, Shintaku P, Said JW, Heber D, Koeffler HP: Ligands for peroxisome proliferator-activated receptor gamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc Natl Acad Sci USA. 1998, 95: 8806-8811. 10.1073/pnas.95.15.8806.CrossRefPubMedPubMedCentral
45.
Motomura W, Okumura T, Takahashi N, Obara T, Kohgo Y: Activation of peroxisome proliferator-activated receptor gamma by troglitazone inhibits cell growth through the increase of p27KiP1 in human pancreatic carcinoma cells. Cancer Res. 2000, 60: 5558-5564.PubMed
46.
Clay CE, Namen AM, Atsumi G, Willingham MC, High KP, Kute TE, Trimboli AJ, Fonteh AN, Dawson PA, Chilton FH: Influence of J series prostaglandins on apoptosis and tumorigenesis of breast cancer cells. Carcinogenesis. 1999, 20: 1905-1911. 10.1093/carcin/20.10.1905.CrossRefPubMed
47.
Chintharlapalli S, Papineni S, Baek SJ, Liu S, Safe S: 1,1-Bis(3'-indolyl)-1-(p-substitutedphenyl)methanes are peroxisome proliferator-activated receptor gamma agonists but decrease HCT-116 colon cancer cell survival through receptor-independent activation of early growth response-1 and NAG-1. Mol Pharmacol. 2005, 68: 1782-1792.PubMed
48.
Chintharlapalli S, Papineni S, Liu S, Jutooru I, Chadalapaka G, Cho SD, Murthy R, You YJ, Safe S: 2-Cyano-lup-1-en-3-oxo-20-oic acid, a cyano derivative of betulinic acid, activates peroxisome proliferator-activated receptor γ in colon and pancreatic cancer cells. Carcinogenesis. 2007, 28: 2337-2346. 10.1093/carcin/bgm189.CrossRefPubMed
49.
Ray DM, Akbiyik F, Phipps RP: The peroxisome proliferator-activated receptor gamma (PPARgamma) ligands 15-deoxy-Delta12,14-prostaglandin J2 and ciglitazone induce human B lymphocyte and B cell lymphoma apoptosis by PPARgamma-independent mechanisms. J Immunol. 2006, 177: 5068-5076.CrossRefPubMed
50.
Chaffer CL, Thomas DM, Thompson EW, Williams ED: PPARgamma-independent induction of growth arrest and apoptosis in prostate and bladder carcinoma. BMC Cancer. 2006, 6: 53-10.1186/1471-2407-6-53.CrossRefPubMedPubMedCentral
51.
Shiau CW, Yang CC, Kulp SK, Chen KF, Chen CS, Huang JW, Chen CS: Thiazolidenediones mediate apoptosis in prostate cancer cells in part through inhibition of Bcl-xL/Bcl-2 functions independently of PPARgamma. Cancer Res. 2005, 65: 1561-1569. 10.1158/0008-5472.CAN-04-1677.CrossRefPubMed
52.
Huang JW, Shiau CW, Yang YT, Kulp SK, Chen KF, Brueggemeier RW, Shapiro CL, Chen CS: Peroxisome proliferator-activated receptor gamma-independent ablation of cyclin D1 by thiazolidinediones and their derivatives in breast cancer cells. Mol Pharmacol. 2005, 67: 1342-1348. 10.1124/mol.104.007732.CrossRefPubMed
53.
Edinger AL, Thompson CB: Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol. 2004, 16: 663-669. 10.1016/j.ceb.2004.09.011.CrossRefPubMed
54.
Zong WX, Ditsworth D, Bauer DE, Wang ZQ, Thompson CB: Alkylating DNA damage stimulates a regulated form of necrotic cell death. Genes Dev. 2004, 18: 1272-1282. 10.1101/gad.1199904.CrossRefPubMedPubMedCentral
55.
Debnath J, Baehrecke EH, Kroemer G: Does autophagy contribute to cell death?. Autophagy. 2005, 1: 66-74. 10.4161/auto.1.2.1738.CrossRefPubMed
56.
Pedro M, Lourenco CF, Cidade H, Kijjoa A, Pinto M, Nascimento MS: Effects of natural prenylated flavones in the phenotypical ER (+) MCF-7 and ER (-) MDA-MB-231 human breast cancer cells. Toxicol Lett. 2006, 164: 24-36. 10.1016/j.toxlet.2005.11.007.CrossRefPubMed
57.
Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y: In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell. 2004, 15: 1101-1111. 10.1091/mbc.E03-09-0704.CrossRefPubMedPubMedCentral
58.
Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, Ishihara N, Mizushima N, Tanida I, Kominami E, Ohsumi M, et al: A ubiquitin-like system mediates protein lipidation. Nature. 2000, 408: 488-492. 10.1038/35044114.CrossRefPubMed
59.
Paglin S, Lee NY, Nakar C, Fitzgerald M, Plotkin J, Deuel B, Hackett N, McMahill M, Sphicas E, Lampen N, et al: Rapamycin-sensitive pathway regulates mitochondrial membrane potential, autophagy, and survival in irradiated MCF-7 cells. Cancer Res. 2005, 65: 11061-11070. 10.1158/0008-5472.CAN-05-1083.CrossRefPubMed
60.
Scarlatti F, Bauvy C, Ventruti A, Sala G, Cluzeaud F, Vandewalle A, Ghidoni R, Codogno P: Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1. J Biol Chem. 2004, 279: 18384-18391. 10.1074/jbc.M313561200.CrossRefPubMed
61.
Lamparska-Przybysz M, Gajkowska B, Motyl T: Cathepsins and BID are involved in the molecular switch between apoptosis and autophagy in breast cancer MCF-7 cells exposed to camptothecin. J Physiol Pharmacol. 2005, 56 (Suppl 3): 159-179.PubMed
Metadata
Title
1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes induce autophagic cell death in estrogen receptor negative breast cancer
Authors
Kathy Vanderlaag
Yunpeng Su
Arthur E Frankel
Robert C Burghardt
Rola Barhoumi
Gayathri Chadalapaka
Indira Jutooru
Stephen Safe
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2010
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-10-669

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