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Oleanane triterpenoids in the prevention and therapy of breast cancer: current evidence and future perspectives

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Abstract

Breast cancer is one of the most frequently diagnosed cancers and major cause of death in women in the world. Emerging evidence underscores the value of dietary and non-dietary phytochemicals, including triterpenoids, in the prevention and treatment of breast cancer. Oleanolic acid, an oleanane-type pentacyclic triterpenoid, is present in a large number of dietary and medicinal plants. Oleanolic acid and its derivatives exhibit several promising pharmacological activities, including antioxidant, anti-inflammatory, hepatoprotective, cardioprotective, antipruritic, spasmolytic, antiallergic, antimicrobial and antiviral effects. Numerous studies indicate that oleanolic acid and other oleanane triterpenoids modulate multiple intracellular signaling pathways and exert chemopreventive and antitumor activities in various in vitro and in vivo model systems. A series of novel synthetic oleanane triterpenoids have been prepared by chemical modifications of oleanolic acid and some of these compounds are considered to be the most potent anti-inflammatory and anticarcinogenic triterpenoids. Accumulating studies provide extensive evidence that synthetic oleanane derivatives inhibit proliferation and induce apoptosis of various cancer cells in vitro and demonstrate cancer preventive or antitumor efficacy in animal models of blood, breast, colon, connective tissue, liver, lung, pancreas, prostate and skin cancer. This review critically examines the potential role of oleanolic acid, oleanane triterpenoids and related synthetic compounds in the chemoprevention and treatment of mammary neoplasia. Both in vitro and in vivo studies on these agents and related molecular mechanisms are presented. Several challenges and future directions of research to translate already available impressive preclinical knowledge to clinical practice of breast cancer prevention and therapy are also presented.

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Abbreviations

AML:

Acute myelogenous leukemia

AMR:

Amooranin

AMR-Me:

Amooranin-methyl

CDDO:

2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid

CDDO-EA:

CDDO-ethyl amide

CDDO-Me:

CDDO-methyl

CDDO-Im:

CDDO-imidazolide

CDDO-TFEA:

CDDO-trifluoroethyl amide

CKD:

Chronic kidney disease

COX-2:

Cyclooxygenase 2

DMBA:

Dimethylbenz(a)anthracene

DR:

Death receptor

eGFR:

Estimated glomerular filtration rate

EGFR:

Epidermal growth factor receptor

ER:

Estrogen receptor

FLIPL :

FLICE-like inhibitory protein

HER2:

Human epidermal growth factor receptor 2

HSP90:

Heat shock protein 90

IκB-α:

Inhibitory kappaB-alpha

i.p.:

Intraperitonial

i.v.:

Intravenous

JAK1:

Janus-activated kinase-1

JNK:

c-Jun N-terminal kinase

MAPK:

Mitogen-activated protein kinase

M-CSF:

Macrophage-colony stimulating factor

MTD:

Maximum tolerated dose

MMP-9:

Matrix metalloproteinase-9

MMTV:

Mouse mammary tumor virus

mTORC1:

Mammalian target of rapamycin complex 1

NF-κB:

Nuclear factor-kappaB

NMU:

N-nitrosomethyl urea

PARP:

Poly(ADP-ribose) polymerase

PPARγ:

Peroxisome proliferator-activated receptor-gamma

PI3K:

Phosphatidylinositide 3-kinase

PyMT:

Polyoma middle T

ROS:

Reactive oxygen species

SAHA:

Suberoylanilide hydroxamic acid

STAT3:

Signal transducer and activator of transcription 3

TAM:

Tumor-associated macrophages

TRAIL:

Tumor necrosis factor-related apoptosis-inducing ligand

References

  • Ahmad R, Raina D, Meyer C, Kufe D (2008) Triterpenoid CDDO-methyl ester inhibits the Janus-activated kinase-1 (JAK1) → signal transducer and activator of transcription-3 (STAT3) pathway by direct inhibition of JAK1 and STAT3. Cancer Res 68:2920–2926

    CAS  PubMed Central  PubMed  Google Scholar 

  • Aiyer HS, Warri AM, Woode DR, Hilakivi-Clarke L, Clarke R (2012) Influence of berry polyphenols on receptor signaling and cell-death pathways: implications for breast cancer prevention. J Agric Food Chem 60:5693–5708

    CAS  PubMed Central  PubMed  Google Scholar 

  • Allouche Y, Warleta F, Campos M, Sánchez-Quesada C, Uceda M, Beltrán G, Gaforio JJ (2011) Antioxidant, antiproliferative, and pro-apoptotic capacities of pentacyclic triterpenes found in the skin of olives on MCF-7 human breast cancer cells and their effects on DNA damage. J Agric Food Chem 59:121–130

    CAS  PubMed  Google Scholar 

  • American Cancer Society (2013) Retrieved from http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-key-statistics. Accessed 8 Oct 2013

  • Barile E, Fattorusso E, Ialenti A, Ianaro A, Lanzotti V (2007) Paraliane and pepluane diterpenes as anti-inflammatory agents: first insights in structure-activity relationships. Bioorg Med Chem Lett 17:4196–4200

    CAS  PubMed  Google Scholar 

  • Barile E, Borriello M, Di Pietro A, Doreau A, Fattorusso C, Fattorusso E, Lanzotti V (2008) Discovery of a new series of jatrophane and lathyrane diterpenes as potent and specific P-glycoprotein modulators. Org Biomol Chem 6:1756–1762

    CAS  PubMed  Google Scholar 

  • Barthomeuf C, Debiton E, Mshvildadze V, Kemertelidze E, Balansard G (2002) In vitro activity of hederacolchisid A1 compared with other saponins from Hedera colchica against proliferation of human carcinoma and melanoma cells. Planta Med 68:672–675

    CAS  PubMed  Google Scholar 

  • Biersack B, Schobert R (2012) Indole compounds against breast cancer: recent developments. Curr Drug Targets 13:1705–1719

    CAS  PubMed  Google Scholar 

  • Bishayee A (2009) Cancer prevention and treatment with resveratrol: from rodent studies to clinical trials. Cancer Prev Res 2:409–418

    CAS  Google Scholar 

  • Bishayee A, Ahmed S, Brankov N, Perloff M (2011) Triterpenoids as potential agents for the chemoprevention and therapy of breast cancer. Front Biosci 16:980–996

    CAS  Google Scholar 

  • Bishayee A, Thoppil RJ, Waghray A, Kruse JA, Novotny NA, Darvesh AS (2012) Dietary phytochemicals in the chemoprevention and treatment of hepatocellular carcinoma: in vivo evidence, molecular targets, and clinical relevance. Curr Cancer Drug Targets 12:1191–1232

    CAS  PubMed  Google Scholar 

  • Bishayee A, Mandal A, Thoppil RJ, Darvesh AS, Bhatia D (2013) Chemopreventive effect of a novel oleanane triterpenoid in a chemically induced rodent model of breast cancer. Int J Cancer 133:1054–1064

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bode AM, Dong Z (2009) Epigallocatechin 3-gallate and green tea catechins: united they work, divided they fail. Cancer Prev Res 2:514–517

    CAS  Google Scholar 

  • Bozovic-Spasojevic I, Azambuja E, McCaskill-Stevens W, Dinh P, Cardoso F (2012) Chemoprevention for breast cancer. Cancer Treat Rev 38:329–339

    CAS  PubMed  Google Scholar 

  • Campeau PM, Foulkes WD, Tischkowitz MD (2008) Hereditary breast cancer: new genetic developments, new therapeutic avenues. Hum Genet 124:31–42

    CAS  PubMed  Google Scholar 

  • Cazzaniga M, Bonanni B (2012) Breast cancer chemoprevention: old and new approaches. J Biomed Biotechnol 2012:985620

    PubMed Central  PubMed  Google Scholar 

  • Chakravarti B, Maurya R, Siddiqui JA, Bid HK, Rajendran SM, Yadav PP, Konwar R (2012) In vitro anti-breast cancer activity of ethanolic extract of Wrightia tomentosa: role of pro-apoptotic effects of oleanolic acid and urosolic acid. J Ethnopharmacol 142:72–79

    CAS  PubMed  Google Scholar 

  • Chu R, Zhao X, Griffin C, Staub RE, Shoemaker M, Climent J, Leitman D, Cohen I, Shtivelman E, Fong S (2010) Selective concomitant inhibition of mTORC1 and mTORC2 activity in estrogen receptor negative breast cancer cells by BN107 and oleanolic acid. Int J Cancer 127:1209–1219

    CAS  PubMed  Google Scholar 

  • Corea G, Fattorusso E, Lanzotti V, Di Meglio P, Maffia P, Grassia G, Ialenti A, Ianaro A (2005) Discovery and biological evaluation of the novel naturally occurring diterpene pepluanone as antiinflammatory agent. J Med Chem 48:7055–7062

    CAS  PubMed  Google Scholar 

  • Corea G, Di Pietro A, Dumontet C, Fattorusso E, Lanzotti V (2009) Jatrophane diterpenes from Euphorbia spp. as modulators of multidrug resistance in cancer therapy. Phytochem Rev 8:431–447

    CAS  Google Scholar 

  • Costa I, Solanas M, Escrich E (2002) Histopathological characterization of mammary neoplastic lesions induced with 7,12-dimethylbenz(a)anthracene in the rat: a comparative analysis with human breast tumors. Arch Pathol Lab Med 126:915–927

    PubMed  Google Scholar 

  • Council of Scientific and Industrial Research (1972) The wealth of India. A dictionary of Indian raw materials and industrial products. Raw materials, vol 9. Rh-So, Council of Scientific and Industrial Research, New Delhi

  • Crowell PL (1997) Monoterpenes in breast cancer chemoprevention. Breast Cancer Res Treat 46:191–197

    CAS  PubMed  Google Scholar 

  • Crujeiras AB, Díaz-Lagares A, Carreira MC, Amil M, Casanueva FF (2013) Oxidative stress associated to dysfunctional adipose tissue: a potential link between obesity, type 2 diabetes mellitus and breast cancer. Free Radic Res 47:243–256

    CAS  PubMed  Google Scholar 

  • Curigliano G, Goldhirsch A (2011) The triple-negative subtype: new ideas for the poorest prognosis breast cancer. J Natl Cancer Inst 43:108–110

    CAS  Google Scholar 

  • Cuzick J, DeCensi A, Arun B, Brown PH, Castiglione M, Dunn B, Forbes JF, Glaus A, Howell A, von Minckwitz G, Vogel V, Zwierzina H (2011) Preventive therapy for breast cancer: a consensus statement. Lancet Oncol 12:496–503

    CAS  PubMed  Google Scholar 

  • de Kok TM, van Breda SG, Manson MM (2008) Mechanisms of combined action of different chemopreventive dietary compounds: a review. Eur J Nutr 47:51–59

    PubMed  Google Scholar 

  • de Zeeuw D, Akizawa T, Agarwal R, Audhya P, Bakris GL, Chin M, Krauth M, Lambers Heerspink HJ, Meyer CJ, McMurray JJ, Parving HH, Pergola PE, Remuzzi G, Toto RD, Vaziri ND, Wanner C, Warnock DG, Wittes J, Chertow GM (2013) Rationale and trial design of bardoxolone methyl evaluation in patients with chronic kidney disease and type 2 diabetes: the occurrence of renal events (BEACON). Am J Nephrol 37:212–222

    PubMed  Google Scholar 

  • Deng Y, Jiang TY, Sheng S, Tianasoa-Ramamonjy M, Snyder JK (1999) Remangilones A–C, new cytotoxic triterpenes from Physena madagascariensis. J Nat Prod 62:471–476

    CAS  PubMed  Google Scholar 

  • Duan Z, Ames RY, Ryan M, Hornicek FJ, Mankin H, Seiden MV (2009) CDDO-Me, a synthetic triterpenoid, inhibits expression of IL-6 and Stat3 phosphorylation in multi-drug resistant ovarian cancer cells. Cancer Chemother Pharmacol 63:681–689

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dzubak P, Hajduch M, Vydra D, Hustova A, Kvasnica M, Biedermann D, Markova L, Urban M, Sarek J (2006) Pharmacological activities of natural triterpenoids and their therapeutic implications. Nat Prod Rep 23:394–411

    CAS  PubMed  Google Scholar 

  • Eccles SA, Aboagye EO, Ali S, Anderson AS, Armes J et al (2013) Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer. Breast Cancer Res 15:R92

    PubMed Central  PubMed  Google Scholar 

  • Efferth T, Koch E (2011) Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy. Curr Drug Target 12:122–132

    CAS  Google Scholar 

  • El-Alfy TS, Ezzat SM, Hegazy AK, Amer AM, Kamel GM (2011) Isolation of biologically active constituents from Moringa peregrina (Forssk.) Fiori. (family: Moringaceae) growing in Egypt. Pharmacogn Mag 7:109–115

    CAS  PubMed Central  PubMed  Google Scholar 

  • Files JA, Stan DL, Allen SV, Pruthi S (2012) Chemoprevention of breast cancer. Womens Health 8:635–646

    CAS  Google Scholar 

  • Fukumura M, Ando H, Hirai Y, Toriizuka K, Ida Y, Kuchino Y (2009) Achyranthoside H methyl ester, a novel oleanolic acid saponin derivative from Achyranthes fauriei roots, induces apoptosis in human breast cancer MCF-7 and MDA-MB-453 cells via a caspase activation pathway. J Nat Med 63:181–188

    CAS  PubMed  Google Scholar 

  • González-Vallinas M, González-Castejón M, Rodríguez-Casado A, Ramírez de Molina A (2013) Dietary phytochemicals in cancer prevention and therapy: a complementary approach with promising perspectives. Nutr Rev 71:585–599

    PubMed  Google Scholar 

  • Gould MN (1997) Cancer chemoprevention and therapy by monoterpenes. Environ Health Perspect 105:977–979

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gu G, Barone I, Gelsomino L, Giordano C, Bonofiglio D, Statti G, Menichini F, Catalano S, Andò S (2012) Oldenlandia diffusa extracts exert antiproliferative and apoptotic effects on human breast cancer cells through ERα/Sp1-mediated p53 activation. J Cell Physiol 227:3363–3372

    CAS  PubMed  Google Scholar 

  • Gullett NP, Ruhul Amin AR, Bayraktar S, Pezzuto JM, Shin DM, Khuri FR, Aggarwal BB, Surh YJ, Kucuk O (2010) Cancer prevention with natural compounds. Semin Oncol 37:258–281

    CAS  PubMed  Google Scholar 

  • Hao J, Liu J, Wen X, Sun H (2013) Synthesis and cytotoxicity evaluation of oleanolic acid derivatives. Bioorg Med Chem Lett 23:2074–2077

    CAS  PubMed  Google Scholar 

  • Harlev E, Nevo E, Solowey E, Bishayee A (2013) Cancer preventive and curative attributes of plants of the Cactaceae family: a review. Planta Med 79:713–722

    CAS  PubMed  Google Scholar 

  • He X, Liu RH (2007) Triterpenoids isolated from apple peels have potent antiproliferative activity and may be partially responsible for apple’s anticancer activity. J Agric Food Chem 55:4366–4370

    CAS  PubMed  Google Scholar 

  • Honda T, Janosik T, Honda Y, Han J, Liby KT, Williams CR, Couch RD, Anderson AC, Sporn MB, Gribble GW (2004) Design, synthesis and biological evaluation of biotin conjugates of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid for the isolation of the protein targets. J Med Chem 47:4923–4932

    CAS  PubMed  Google Scholar 

  • Hong DS, Kurzrock R, Supko JG, He X, Naing A, Wheler J, Lawrence D, Eder JP, Meyer CJ, Ferguson DA, Mier J, Konopleva M, Konoplev S, Andreeff M, Kufe D, Lazarus H, Shapiro GI, Dezube BJ (2012) A phase I first-in-human trial of bardoxolone methyl in patients with advanced solid tumors and lymphomas. Clin Cancer Res 18:3396–3406

    CAS  PubMed  Google Scholar 

  • Hsu HF, Houng JY, Chang CL, Wu CC, Chang FR, Wu YC (2005) Antioxidant activity, and DNA information of Glossogyne tenuifolia. J Agric Food Chem 53:6117–6125

    PubMed  Google Scholar 

  • Hyer ML, Croxton R, Krajewska M, Krajewski S, Kress CL, Lu M, Suh N, Sporn MB, Cryns VL, Zapata JM, Reed JC (2005) Synthetic triterpenoids co-operate with tumor necrosis factor-related apoptosis-inducing ligand to induce apoptosis of breast cancer cells. Cancer Res 65:4799–4808

    CAS  PubMed  Google Scholar 

  • Jeong DW, Kim YH, Kim HH, Ji HY, Yoo SD, Choi WR, Lee SM, Han CK, Lee HS (2007) Dose-linear pharmacokinetics of oleanolic acid after intravenous and oral administration in rats. Biopharm Drug Dispos 28:51–57

    CAS  PubMed  Google Scholar 

  • Jia Y, Lu Y, Wu K, Lin Q, Shen W, Zhu M, Huang S, Chen J (2013) Does night work increase the risk of breast cancer? A systematic review and meta-analysis of epidemiological studies. Cancer Epidemiol 37:197–206

    PubMed  Google Scholar 

  • Jordan VC (2007) Chemoprevention of breast cancer with selective oestrogen-receptor modulators. Nat Rev Cancer 7:46–53

    CAS  PubMed  Google Scholar 

  • Kado K, Forsyth A, Patel PR, Schwartz JA (2012) Dietary supplements and natural products in breast cancer trials. Front Biosci 4:546–567

    Google Scholar 

  • Kang X, Hu J, Gao Z, Ju Y, Xu C (2012) Synthesis, anti-proliferative and proapoptotic activity of novel oleanolic acid azaheterocyclic derivatives. Med Chem Commun 3:1245–1249

    CAS  Google Scholar 

  • Khan SI, Zhao J, Khan IA, Walker LA, Dasmahapatra AK (2011) Potential utility of natural products as regulators of breast cancer-associated aromatase promoters. Reprod Biol Endocrinol 9:91

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kim EH, Deng CX, Sporn MB, Liby KT (2011) CDDO-imidazolide induces DNA damage, G2/M arrest and apoptosis in BRCA1-mutated breast cancer cells. Cancer Prev Res 4:425–434

    CAS  Google Scholar 

  • Kim EH, Deng C, Sporn MB, Royce DB, Risingsong R, Williams CR, Liby KT (2012) CDDO-methyl ester delays breast cancer development in Brca1-mutated mice. Cancer Prev Res 5:89–97

    CAS  Google Scholar 

  • Kirtikar KR, Basu BD (1980) Indian medicinal plants, 2nd edn. Bishen Singh Mahendra Pal Singh, Dehra Dun

    Google Scholar 

  • Konopleva M, Zhang W, Shi YX, McQueen T, Tsao T, Abdelrahim M, Munsell MF, Johansen M, Yu D, Madden T, Safe SH, Hung MC, Andreeff (2006) Synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces growth arrest in HER2-over expressing breast cancer cells. Mol Cancer Ther 5:317–328

    CAS  PubMed  Google Scholar 

  • Kuttan G, Pratheeshkumar P, Manu KA, Kuttan R (2011) Inhibition of tumor progression by naturally occurring terpenoids. Pharm Biol 49:995–1007

    CAS  PubMed  Google Scholar 

  • Lanzotti V, Termolino P, Dolci M, Curir P (2012) Paviosides A–H, eight new oleane type saponins from Aesculus pavia with cytotoxic activity. Bioorg Med Chem 20:3280–3286

    CAS  PubMed  Google Scholar 

  • Lapillonne H, Konopleva M, Tsao T, Gold D, McQueen T, Sutherland RL, Madden T, Andreeff M (2003) Activation of peroxisome proliferators-activated receptor gamma by a novel synthetic triterpenoid 2-cyano-3,12-dioxoleana-1,9-dien-28oic acid induces growth arrest and apoptosis in breast cancer cells. Cancer Res 63:5926–5939

    CAS  PubMed  Google Scholar 

  • Laszczyk MN (2009) Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in cancer therapy. Planta Med 75:1549–1560

    CAS  PubMed  Google Scholar 

  • Liby KT, Sporn MB (2012) Synthetic oleanane triterpenoids: multifunctional drugs with a broad range of applications for prevention and treatment of chronic disease. Pharmacol Rev 64:972–1003

    CAS  PubMed Central  PubMed  Google Scholar 

  • Liby KT, Yore MM, Sporn MB (2007) Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer. Nat Rev Cancer 7:357–369

    CAS  PubMed  Google Scholar 

  • Liby K, Risingsong R, Royce DB, Williams CR, Yore MM, Honda T, Gribble GW, Lamph WW, Vannini N, Sogno I, Albini A, Sporn MB (2008) Prevention and treatment of experimental estrogen receptor-negative mammary carcinogenesis by the synthetic triterpenoid CDDO-methyl ester and the rexinoid LG100268. Clin Cancer Res 14:4556–4563

    CAS  PubMed  Google Scholar 

  • Lillie SE, Brewer NT, O’Neill SC, Morrill EF, Dees EC, Carey LA, Rimer BK (2007) Retention and use of breast cancer recurrence risk information from genomic tests: the role of health literacy. Cancer Epidemiol Biomarkers Prev 16:249–255

    PubMed  Google Scholar 

  • Ling X, Konopleva M, Zeng Z, Ruvolo V, Stephens LC, Schober W, McQueen T, Dietrich M, Madden TL, Andreeff M (2007) The novel triterpenoid C-28 methyl ester of 2-cyano-3,12-dioxolen-1,9-dien-28-oic acid inhibits metastatic murine breast tumor growth through inactivation of STAT3 signaling. Cancer Res 67:4210–4218

    CAS  PubMed  Google Scholar 

  • Liu RH (2004) Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr 134:3479S–3485S

    CAS  PubMed  Google Scholar 

  • Liu J (2005) Oleanolic acid and ursolic acid: research perspectives. J Ethnopharmacol 100:92–94

    CAS  PubMed  Google Scholar 

  • Malejka-Giganti D, Niehans GA, Reichert MA, Bliss RL (2000) Post-initiation treatment of rats with indole-3-carbinol or beta-naphthoflavone does not suppress 7,12-dimethylbenz[a]anthracene-induced mammary gland carcinogenesis. Cancer Lett 160:209–218

    CAS  PubMed  Google Scholar 

  • Mandal A, Bhatia D, Bishayee A (2013a) Simultaneous disruption of estrogen receptor and Wnt/β-catenin signaling is involved in methyl amooranin-mediated chemoprevention of mammary gland tumorigenesis in rats. Mol Cell Biochem 384:239–250

    CAS  PubMed  Google Scholar 

  • Mandal A, Bhatia D, Bishayee A (2013b) Suppression of inflammatory cascade is implicated in methyl amooranin-mediated inhibition of experimental mammary carcinogenesis. Mol Carcinog (in press)

  • Matysik G, Wójciak-Kosior M, Paduch R (2005) The influence of Calendulae officinalis flos extracts on cell cultures, and the chromatographic analysis of extracts. J Pharm Biomed Anal 38:285–292

    CAS  PubMed  Google Scholar 

  • Mencherini T, Picerno P, Festa M, Russo P, Capasso A, Aquino R (2011) Triterpenoid constituents from the roots of Paeonia rockii ssp. rockii. J Nat Prod 74:2116–2121

    CAS  PubMed  Google Scholar 

  • Miller JA, Thompson PA, Hakim IA, Sherry Chow HH, Thompson CA (2011) d-Limonene: a bioactive food component from citrus and evidence for a potential role in breast cancer prevention and treatment. Oncol Rev 5:31–42

    Google Scholar 

  • Ovesná Z, Vachálková A, Horváthová K, Tóthová D (2004) Pentacyclic triterpenoic acids: new chemoprotective compounds. Minireview. Neoplasma 51:327–333

    PubMed  Google Scholar 

  • Park SY, Kolonel LN, Lim U, White KK, Henderson BE, Wilkens LR (2013) Alcohol consumption and breast cancer risk among women from five ethnic groups with light to moderate intakes: the multiethnic cohort study. Int J Cancer 134:1504–1510

    Google Scholar 

  • Patlolla JM, Rao CV (2012) Triterpenoids for cancer prevention and treatment: current status and future prospects. Curr Pharm Biotechnol 13:147–155

    CAS  PubMed  Google Scholar 

  • Pergola PE, Raskin P, Toto RD, Meyer CJ, Huff JW, Grossman EB, Krauth M, Ruiz S, Audhya P, Christ-Schmidt H, Wittes J, Warnock DG (2011a) Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N Engl J Med 365:327–336

    CAS  PubMed  Google Scholar 

  • Pergola PE, Krauth M, Huff JW, Ferguson DA, Ruiz S, Meyer CJ, Warnock DG (2011b) Effect of bardoxolone methyl on kidney function in patients with T2D and Stage 3b-4 CKD. Am J Nephrol 33:469–476

    CAS  PubMed  Google Scholar 

  • Petronelli A, Pannitteri G, Testa U (2009) Triterpenoids as new promising anticancer drugs. Anticancer Drugs 20:880–892

    CAS  PubMed  Google Scholar 

  • Pierobon M, Frankenfeld CL (2013) Obesity as a risk factor for triple-negative breast cancers: a systematic review and meta-analysis. Breast Cancer Res Treat 137:307–314

    PubMed  Google Scholar 

  • Place AE, Suh N, Williams CR, Risingsong R, Honda T, Honda Y, Gribble GW, Leesnitzer LM, Stimmel JB, Willson TM, Rosen E, Sporn MB (2003) The novel synthetic triterpenoid, CDDO-imidazolide, inhibits inflammatory response and tumor growth in vivo. Clin Cancer Res 9:2798–2806

    CAS  PubMed  Google Scholar 

  • Pollier J, Goossens A (2012) Oleanolic acid. Phytochemistry 77:10–15

    CAS  PubMed  Google Scholar 

  • Pollier J, Moses T, Goossens A (2011) Combinatorial biosynthesis in plants: a (p)review on its potential and future exploitation. Nat Prod Rep 28:1897–1916

    CAS  PubMed  Google Scholar 

  • Prasad GC (1987) Studies on cancer in Ayurveda and its management. J Res Ayurveda Siddha 8:147–167

    Google Scholar 

  • Rabi T (1996) Antitumor activity of amooranin from Amoora rohituka stem bark. Curr Sci 70:80–81

    CAS  Google Scholar 

  • Rabi T, Banerjee S (2008) Novel synthetic triterpenoid methyl 25-hydroxy-3-oxoolean-12-en-28-oate induces apoptosis through JNK and p38 MAPK pathways in human breast adenocarcinoma MCF-7 cells. Mol Carcinog 47:415–423

    CAS  PubMed  Google Scholar 

  • Rabi T, Bishayee A (2009) Terpenoids and breast cancer chemoprevention. Breast Cancer Res Treat 115:223–239

    CAS  PubMed  Google Scholar 

  • Rabi T, Gupta S (2008) Dietary terpenoids and prostate cancer chemoprevention. Front Biosci 13:3457–3469

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rabi T, Karunagaram D, Nair MK, Bhattathiri VN (2002) Cytotoxic activity of amooranin and its derivatives. Phytother Res 16:S84–S86

    CAS  PubMed  Google Scholar 

  • Rabi T, Ramachandran C, Fonseca HB, Nair RP, Alamo A, Melnick SJ, Escalon E (2003) Novel drug amooranin induces apoptosis through caspase activity in human breast carcinoma cell lines. Breast Cancer Res Treat 80:321–330

    CAS  PubMed  Google Scholar 

  • Rabi T, Wang L, Banerjee S (2007) Novel triterpenoid 25-hydroxy-3-oxoolean-12-en-28-oic acid induces growth arrest and apoptosis in breast cancer cells. Breast Cancer Res Treat 101:27–36

    CAS  PubMed  Google Scholar 

  • Rabi T, Huwiler A, Zangemeister-Wittke U (2013) AMR-Me inhibits PI3K/Akt signaling in hormone-dependent MCF-7 breast cancer cells and inactivates NF-κB in hormone-independent MDA-MB-231 cells. Mol Carcinog (in press)

  • Reuben SC, Gopalan A, Petit DM, Bishayee A (2012) Modulation of angiogenesis by dietary phytoconstituents in the prevention and intervention of breast cancer. Mol Nutr Food Res 56:14–29

    CAS  PubMed  Google Scholar 

  • Safe SH, Prather PL, Brents LK, Chadalapaka G, Jutooru I (2012) Unifying mechanisms of action of the anticancer activities of triterpenoids and synthetic analogs. Anticancer Agents Med Chem 12:1211–1220

    CAS  PubMed Central  PubMed  Google Scholar 

  • Setzer WN, Setzer MC (2003) Plant-derived triterpenoids as potential antineoplastic agents. Mini Rev Med Chem 3:540–556

    CAS  PubMed  Google Scholar 

  • Shan JZ, Xuan YY, Ruan SQ, Sun M (2011) Proliferation-inhibiting and apoptosis-inducing effects of ursolic acid and oleanolic acid on multi-drug resistance cancer cells in vitro. Chin J Integr Med 17:607–611

    CAS  PubMed  Google Scholar 

  • Shanmugam MK, Nguyen AH, Kumar AP, Tan BK, Sethi G (2012) Targeted inhibition of tumor proliferation, survival, and metastasis by pentacyclic triterpenoids: potential role in prevention and therapy of cancer. Cancer Lett 320:158–170

    CAS  PubMed  Google Scholar 

  • Shanmugam MK, Dai X, Kumar AP, Tan BK, Sethi G, Bishayee A (2013) Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies. Biochem Pharmacol 85:1579–1587

    CAS  PubMed  Google Scholar 

  • Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30

    PubMed  Google Scholar 

  • Sinha D, Biswas J, Sung B, Aggarwal BB, Bishayee A (2012) Chemopreventive and chemotherapeutic potential of curcumin in breast cancer. Curr Drug Targets 13:1799–1819

    CAS  PubMed  Google Scholar 

  • Sogno I, Vannini N, Lorusso G, Cammarota R, Noonan DM, Generoso L, Sporn MB, Albini A (2009) Anti-angiogenic activity of a novel class of chemopreventive compounds: oleanic acid terpenoids. Recent Results Cancer Res 181:209–212

    CAS  PubMed  Google Scholar 

  • Somova LO, Nadar A, Rammanan P, Shode FO (2003) Cardiovascular, antihyperlipidemic and antioxidant effects of oleanolic and ursolic acids in experimental hypertension. Phytomedicine 10:115–121

    CAS  PubMed  Google Scholar 

  • Song M, Hang TJ, Wang Y, Jiang L, Wu XL, Zhang Z, Shen J, Zhang Y (2006) Determination of oleanolic acid in human plasma and study of its pharmacokinetics in Chinese healthy male volunteers by HPLC tandem mass spectrometry. J Pharm Biomed Anal 40:190–196

    CAS  PubMed  Google Scholar 

  • Speranza G, Gutierrez ME, Kummar S, Strong JM, Parker RJ, Collins J, Yu Y, Cao L, Murgo AJ, Doroshow JH, Chen A (2012) Phase I study of the synthetic triterpenoid, 2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid (CDDO), in advanced solid tumors. Cancer Chemother Pharmacol 69:431–438

    CAS  PubMed  Google Scholar 

  • Sporn MB, Liby KT, Yore MM, Fu L, Lopchuk JM, Gribble GW (2011) New synthetic triterpenoids: potent agents for prevention and treatment of tissue injury caused by inflammatory and oxidative stress. J Nat Prod 74:537–545

    CAS  PubMed Central  PubMed  Google Scholar 

  • Suh N, Wang Y, Honda T, Gribble GW, Dmitrovsky E, Hickey WF, Maue RA, Place AE, Porter DM, Spinella MJ, Williams CR, Wu G, Dannenberg AJ, Flanders KC, Letterio JJ, Mangelsdorf DJ, Nathan CF, Nguyen L, Porter WW, Ren RF, Roberts AB, Roche NS, Subbaramaiah K, Sporn MB (1999) A novel synthetic oleanane triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, with potent differentiating, antiproliferative, and anti-Inflammatory activity. Cancer Res 59:336–341

    CAS  PubMed  Google Scholar 

  • Sultana N, Ata A (2008) Oleanolic acid and related derivatives as medicinally important compounds. J Enzyme Inhib Med Chem 23:739–756

    CAS  PubMed  Google Scholar 

  • Szakiel A, Ruszkowski D, Janiszowska W (2005) Saponins in Calendula officinalis L.—structure, biosynthesis, transport and biological activity. Phytochem Rev 4:151–158

    CAS  Google Scholar 

  • Tang W, Eisenbrand G (1992) Chinese drugs of plant origin. Springer, Berlin

    Google Scholar 

  • Thoppil RJ, Bishayee A (2011) Terpenoids as potential chemopreventive and therapeutic agents in liver cancer. World J Hepatol 3:228–249

    PubMed Central  PubMed  Google Scholar 

  • Tran K, Risingsong R, Royce D, Williams CR, Sporn MB, Liby K (2012) The synthetic triterpenoid CDDO-methyl ester delays estrogen receptor-negative mammary carcinogenesis in polyoma middle T mice. Cancer Prev Res 5:726–734

    CAS  Google Scholar 

  • Tran K, Risingsong R, Royce DB, Williams CR, Sporn MB, Pioli PA, Gediya LK, Njar VC, Liby KT (2013) The combination of the histone deacetylase inhibitor vorinostat and synthetic triterpenoids reduces tumorigenesis in mouse models of cancer. Carcinogenesis 34:199–210

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tsao T, Kornblau S, Safe S, Watt JC, Ruvolo V, Chen W, Qiu Y, Coombes KR, Ju Z, Abdelrahim M, Schober W, Ling X, Kardassis D, Meyer C, Schimmer A, Kantarjian H, Andreeff M, Konopleva M (2010) Role of peroxisome proliferator-activated receptor-gamma and its coactivator DRIP205 in cellular responses to CDDO (RTA-401) in acute myelogenous leukemia. Cancer Res 70:4949–4960

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ulrich-Merzenich G, Zeitler H, Vetter H, Kraft K (2009) Synergy research: vitamins and secondary plant components in the maintenance of the redox-homeostasis and in cell signaling. Phytomedicine 16:2–16

    CAS  PubMed  Google Scholar 

  • Vadodkar AS, Suman S, Lakshmanaswamy R, Damodaran C (2012) Chemoprevention of breast cancer by dietary compounds. Anticancer Agents Med Chem 12:1185–1202

    CAS  PubMed  Google Scholar 

  • Venugopal R, Liu RH (2012) Phytochemicals in diets for breast cancer prevention: the importance of resveratrol and ursolic acid. Food Sci Hum Wellness 1:1–13

    Google Scholar 

  • Wang X, Ye XL, Liu R, Chen HL, Bai H, Liang X, Zhang XD, Wang Z, Li WL, Hai CX (2010) Antioxidant activities of oleanolic acid in vitro: possible role of Nrf2 and MAP kinases. Chem Biol Interact 184:328–337

    CAS  PubMed  Google Scholar 

  • Withers ST, Keasling JD (2007) Biosynthesis and engineering of isoprenoid small molecules. Appl Microbiol Biotechnol 73:980–990

    CAS  PubMed  Google Scholar 

  • Yadav VR, Prasad S, Sung B, Kannappan R, Aggarwal BB (2010) Targeting inflammatory pathways by triterpenoids for prevention and treatment of cancer. Toxins 2:2428–2466

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yang H, Dou QP (2010) Targeting apoptosis pathway with natural terpenoids: implications for treatment of breast and prostate cancer. Curr Drug Targets 11:733–744

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yiannakopoulou EC (2014) Effect of green tea catechins on breast carcinogenesis: a systematic review of in vitro and in vivo experimental studies. Eur J Cancer Prev 23:84–89

    Google Scholar 

  • Yin MC, Lin MC, Mong MC, Lin CY (2012) Bioavailability, distribution, and antioxidative effects of selected triterpenes in mice. J Agric Food Chem 60:7697–7701

    CAS  PubMed  Google Scholar 

  • Yun BS, Ryoo IJ, Lee IK, Park KH, Choung DH, Han KH, Yoo ID (1999) Two bioactive pentacyclic triterpene esters from the root bark of Hibiscus syriacus. J Nat Prod 62:764–766

    CAS  PubMed  Google Scholar 

  • Zhang W, Popovich DG (2009) Chemical and biological characterization of oleanane triterpenoids from soy. Molecules 14:2959–2975

    CAS  PubMed  Google Scholar 

  • Zhang H, Boghigian BA, Armando J, Pfeifer BA (2011) Methods and options for the heterologous production of complex natural products. Nat Prod Rep 28:125–151

    PubMed  Google Scholar 

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Acknowledgments

The research on triterpenoid and breast cancer chemoprevention at the corresponding author’s laboratory is supported by the award R03CA136014 from the National Cancer Institute/National Institutes of Health. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

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  1. Department of Pharmaceutical Sciences, School of Pharmacy, American University of Health Sciences, Signal Hill, CA, 90755, USA

    Nisha R. Parikh & Anupam Bishayee

  2. Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH, 44272, USA

    Animesh Mandal & Deepak Bhatia

  3. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore

    Kodappully Sivaraman Siveen

  4. Department of Pharmacology, Yong Loo Lin School of Medicine, Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117597, Singapore

    Gautam Sethi

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  1. Nisha R. Parikh
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Correspondence to Anupam Bishayee.

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Parikh, N.R., Mandal, A., Bhatia, D. et al. Oleanane triterpenoids in the prevention and therapy of breast cancer: current evidence and future perspectives. Phytochem Rev 13, 793–810 (2014). https://doi.org/10.1007/s11101-014-9337-5

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