Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells.
BACKGROUND
Ziziphus extracts have been used in Traditional Chinese Medicine for the treatment of cancer.


OBJECTIVE
In the present study we have investigated the effects of Ziziphus jujube extracts (ZEs) on breast cancer.


METHODS
We evaluated the effects of increasing concentrations of ZEs on ERα positive MCF-7 and ERα negative SKBR3 breast cancer cell proliferation using MTT assays. Apoptosis was analyzed by evaluating the involvement of some pro-apoptotic proteins, including Bax, Bad, Bid and PARP cleavage by immunoblotting analysis. Moreover, the effects of ZEs treatment on apoptosis were tested by both DNA fragmentation and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) staining. By using chromatographic techniques, we identified the constituents of the effective extracts.


RESULTS
ZE1, ZE2, and ZE4 exerted significant antiproliferative effects on estrogen receptor alpha (ERα) positive MCF-7 (IC(50) values of 14.42, 7.64, 1.69μg/mL) and ERα negative SKBR3 (IC(50) values of 14.06, 6.21, 3.70μg/mL) human breast cancer cells. Remarkably, ZEs did not affect cell viability of both normal human fibroblasts BJ1-hTERT and nonmalignant breast epithelial MCF-10A cells. Treatment with ZEs induced cell death by apoptosis in both malignant breast cells. We found that the most effective extracts ZE2 and ZE4 shared a number of triterpenic acids, already known for their anticancer activities.


CONCLUSIONS
Our data provide a rational base for the use of Ziziphus extracts in the treatment of breast cancer in Traditional Chinese Medicine.
Department of Pharmaceutical Sciences, University of Calabria, 87036 Arcavacata di Rende, Cosenza, Italy. p.plastina@unical.it
Pierluigi
P
Plastina
Daniela
D
Bonofiglio
Donatella
D
Vizza
Alessia
A
Fazio
Daniela
D
Rovito
Cinzia
C
Giordano
Ines
I
Barone
Stefania
S
Catalano
Bartolo
B
Gabriele
D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001940:Breast / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005638:Fruit / Q000737:chemistry; D006801:Humans; D020287:In Situ Nick-End Labeling; D008516:Medicine, Chinese Traditional; D008517:Phytotherapy; D014315:Triterpenes / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D031957:Ziziphus / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D047628:Estrogen Receptor alpha; D014315:Triterpenes