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Antiproliferative and Cytotoxic Activities

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Sesquiterpene Lactones

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.

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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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Authors and Affiliations

  1. Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Farmacología, Cátedra de Farmacognosia, Buenos Aires, Argentina

    Claudia A. Anesini & María Rosario Alonso

  2. CONICET – Universidad de Buenos Aires, Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), Buenos Aires, Argentina

    Claudia A. Anesini & María Rosario Alonso

  3. Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología, Cátedra de Inmunología, Buenos Aires, Argentina

    Renzo F. Martino

Authors
  1. Claudia A. Anesini
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  2. María Rosario Alonso
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  3. Renzo F. Martino
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Editors and Affiliations

  1. University of Buenos Aires, CONICET University of Buenos Aires, Autonomous City of Buenos Aires, Buenos Aires, Argentina

    Valeria Patricia Sülsen

  2. University of Buenos Aires, CONICET University of Buenos Aires, Autonomous City of Buenos Aires, Buenos Aires, Argentina

    Virginia Susana Martino

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Anesini, C.A., Alonso, M.R., Martino, R.F. (2018). Antiproliferative and Cytotoxic Activities. In: Sülsen, V., Martino, V. (eds) Sesquiterpene Lactones. Springer, Cham. https://doi.org/10.1007/978-3-319-78274-4_13

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