Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells

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• 作者：Pierluigi Plastina^a ; ^{p.plastina@unical.it} ; Daniela Bonofiglio^b ; ^c ; Donatella Vizza^b ; ^c ; Alessia Fazio^a ; Daniela Rovito^b ; ^c ; Cinzia Giordano^c ; Ines Barone^c ; ^d ; Stefania Catalano^b ; ^c ; Bartolo Gabriele^a ; ^{b.gabriele@unical.it}
• 关键词：AcOEt ; ethyl acetate ; n-BuOH ; 1-buthanol ; cs ; charcoal-stripped ; DPPH ; 1 ; 1-diphenyl-2-picryl hydrazyl ; DW ; dry weight ; ER¦Á ; estrogen receptor alpha ; FBS ; fetal bovine serum ; FID ; flame ionization detector ; GLC ; gas&ndash ; liquid chromatography ; MTT ; 3-(4
• 刊名：Journal of Ethnopharmacology
• 出版年：2012
• 出版时间：27 March, 2012
• 年：2012
• 卷：140
• 期：2
• 页码：325-332
• 全文大小：797 K

文摘

Ethnopharmacological relevance

Ziziphus extracts have been used in Traditional Chinese Medicine for the treatment of cancer.

Aim of the study

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

Materials and methods

We evaluated the effects of increasing concentrations of ZEs on ER¦Á positive MCF-7 and ER¦Á 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 (ER¦Á) positive MCF-7 (IC₅₀ values of 14.42, 7.64, 1.69 ¦Ìg/mL) and ER¦Á negative SKBR3 (IC₅₀ values of 14.06, 6.21, 3.70 ¦Ìg/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.