Phytochemistry Reviews

, Volume 13, Issue 4, pp 793–810

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

  • Nisha R. Parikh
  • Animesh Mandal
  • Deepak Bhatia
  • Kodappully Sivaraman Siveen
  • Gautam Sethi
  • Anupam Bishayee
Article

DOI: 10.1007/s11101-014-9337-5

Cite this article as:
Parikh, N.R., Mandal, A., Bhatia, D. et al. Phytochem Rev (2014) 13: 793. doi:10.1007/s11101-014-9337-5

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.

Keywords

Chemoprevention Mammary cancer Oleanolic acid Synthetic oleananes Treatment 

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

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Nisha R. Parikh
    • 1
  • Animesh Mandal
    • 2
  • Deepak Bhatia
    • 2
  • Kodappully Sivaraman Siveen
    • 3
  • Gautam Sethi
    • 4
  • Anupam Bishayee
    • 1
  1. 1.Department of Pharmaceutical Sciences, School of PharmacyAmerican University of Health SciencesSignal HillUSA
  2. 2.Department of Pharmaceutical Sciences, College of PharmacyNortheast Ohio Medical UniversityRootstownUSA
  3. 3.Department of Pharmacology, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
  4. 4.Department of Pharmacology, Yong Loo Lin School of Medicine, Cancer Science Institute of SingaporeNational University of SingaporeSingaporeSingapore

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