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Antiproliferative and Cytotoxic Activities

  • Claudia A. Anesini
  • María Rosario Alonso
  • Renzo F. Martino
Chapter

Abstract

Cancer is a genetic disease, affecting many people worldwide. Chemotherapy is routinely used for cancer treatment. However, this therapeutic approach is not always effective due to the development of cell resistance and toxic effects. Plants are a reservoir of natural chemicals with chemoprotective potential against cancer and with low adverse effects. While some drugs from natural origin are currently used for cancer treatment, others are being studied. Among the compounds isolated from plants, sesquiterpene lactones are very promising anticancer agents, which are widely being studied in different models of cancer in vitro and in vivo, and some clinical trials are being performed. Sesquiterpene lactones are very attractive compounds to be used as antitumoral therapy due to the diverse mechanisms of action through which they exert their effects. Among such mechanisms are their capacity to interfere with the generation of reactive oxygen species, the epigenetic modulation of gene expression, the targeting of the sarco-/endoplasmic reticulum calcium ATPase pump, and the activation of the NF-kB and the p53 signaling pathways. The latter mechanisms could be important to reduce the development of drug resistance by tumor cells. Sesquiterpene lactones can also inhibit angiogenesis and metastasis.

Keywords

Cancer Sesquiterpene lactones Mechanism of action In vitro studies In vivo studies Clinical trials 

Abbreviations

ALCLs

Anaplastic large cell lymphomas

ALL

Acute lymphoblastic leukemia

AML

Acute myeloid leukemia

APL

Acute promyelocytic leukemia

Bax

Apoptosis regulator BAX

Bcl- 2

B-cell CLL/lymphoma 2

Bid

BH3 interacting domain death agonist

BL

Burkitt lymphoma

BZLF1

Human herpes virus (E′stein-Barr virus) gene

Caspases

Cysteine aspartate-specific proteases

CCRF-CEM cells

Cellosaurus acute lymphoblastic leukemia cell line

CCRF/ADR 5000

Cellosaurus cell line, a doxorubicin-resistant sub-line derived from drug-sensitive, parental CCRF-CEM cells

Cdc2

Cell division control protein 2

c-FLIP

Cellular FLICE-like inhibitory protein

CLL

Chronic lymphocytic leukemia

CML

Chronic myeloid leukemia

c-Src

Proto-oncogene tyrosine-protein kinase

C/EBP

CHOP homologus protein

GADD 153

DNA damage inducible gene 153

DU-145

Human prostate carcinoma cell line

EGFR

EGFR/PI3K/Akt signaling pathway

EBV

Raji cell line: Epstein Barr virus (EBV)-positive Burkitt lymphoma (BL) cell line

ER

Endoplasmic reticulum

ERK

Extracellular signal-regulated kinase

HDAC1

Histone deacetylase 1

HeLa

Immortal cell line

HepG2

Human liver cancer cell line

HIN-1

Histidine nucleotide-binding protein 1

HL

Hodgkin lymphoma

HL-60

Acute myeloid leukemia

HSCs

Healthy hematopoietic stem cells

HT 29

Human colorectal adenocarcinoma

CML

Human chronic myeloid leukemia (CML) K562 cells

HL

Human leukemia HL-60 cells

IkB

Inhibitor of NF-kB

IKK

NF-κB kinase

JNK

C-Jun N-terminal kinase

Jun B

Transcription factor of the tyrosine receptor kinase PDGF-Rβ

LSCs

Leukemic stem cells

MAPK

Mitogen activated protein kinases

MCF-7

Breast cancer cells

MCF7

Human breast adenocarcinoma cell line

MDA-MB 435

Melanoma cell line

MDA-MB-231

Human breast cancer cell line

MDM2

Mouse double minute 2 homolog protein

MIA-PaCa-2 cells

Human pancreatic carcinoma cell lines

MDR P-gp CEM/ADR5000 cells

Multidrug-resistant P-gp over expressing CEM/ADR5000 leukemic cells

NF-κB

Nuclear factor kappa-light-chain-enhancer of activated B cells

NHL

Non-Hodgkin lymphoma

NIH/3T3

Normal fibroblast cell line

NPM-ALK

Nucleophosmin-anaplastic lymphoma kinase

p21

Protein P21

P-38

Protein kinase P-38

p53

Protein P53

PARP 1

Poly-(ADP-ribose) polymerase1

PBMC

Peripheral blood mononuclear cells

PC-3

Human prostate grade IV adenocarcinoma cell line

PDGF-Rβ

Beta-type platelet-derived growth factor receptor

PI3K

Phosphatidylinositol-3-kinase

PKCα

Protein kinase C alpha

PKCβII

Protein kinase β

RIPK1

Receptor interacting protein kinase 1

ROS

Reactive oxygen species

SW872

Cellosaurus cell line SW 872, liposarcoma

SW982

Cellosaurus cell line SW 982, biphasic synovial sarcoma

TE-671

Cellosaurus cell line T-671, a human rhabdomyosarcoma

SER

Sarcoplasmic/endoplasmic reticulum

SERCA

Sarco/endoplasmic reticulum calcium ATPase

Smac/Diablo

Mitochondria-derived activator of caspases

SMMC-7721

Human hepatocarcinoma cell line

STAT

Signal transducer and activator of transcription

TNFα

Tumor necrosis factor-α

TRAIL

TNF-related apoptosis-inducing ligand

U251MG

Glioblastoma cell line

U937

Histiocytic lymphoma cell line

Ub

Ubiquitin

UPR

Unfolded protein response

Walker-256

Rat breast carcinoma cell line

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Claudia A. Anesini
    • 1
    • 2
  • María Rosario Alonso
    • 1
    • 2
  • Renzo F. Martino
    • 3
  1. 1.Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Farmacología, Cátedra de FarmacognosiaBuenos AiresArgentina
  2. 2.CONICET – Universidad de Buenos Aires, Instituto de Química y Metabolismo del Fármaco (IQUIMEFA)Buenos AiresArgentina
  3. 3.Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología, Cátedra de InmunologíaBuenos AiresArgentina

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