A COX-2 inhibitor nimesulide analog selectively induces apoptosis in Her2 overexpressing breast cancer cells via cytochrome c dependent mechanisms

Breast cancer is a common disease diagnosed in women. The therapies for breast cancer often have side effects and the most effective drugs are highly toxic. Finding safe alternative medicines is an important goal in the search for a cure for breast cancer. Bromelains are a mixture of cysteine proteases extracted from pineapple. Pineapple is considered to be a safe food. In this paper, the breast cancer cell lines MCF7 and MDA-MB-231 were co-cultured with bromelains extracted from different tissues of the pinapple. Results showed that the growth of MCF7 and MDA-MB-231 cells can be inhibited by bromelains. The bromelains for this study were extracted from the fruit pulp, peel, fruit stalk, young stem, and mature stem. Bromelains extracted from the fruit stalk were found to be the most effective for inhibiting the growth of breast cancer cells. MCF7 was more sensitive to bromelains than MDA-MB-231. After the breast cancer cells were co-cultured with the bromelain, the transcripts of p53 and Bax increased significantly. The transcriptional expressions of Cox-2 and Bcl-2 were down-regulated. More proteins of p53 and Bax were produced. The translational expressions of Cox-2 and Bcl-2 were both down-regulated. Bromelains inhibited the growth of BC cells through the up-regulating of p53, Bax, and by decreasing the expressions of Cox-2 and Bcl-2. The activity of nuclear factor-kappa B (NF-κB) might be blocked. Final effects might be performed by regulating the functions of the protein kinase.

Download Full-text

Sanguinarine inhibits invasiveness and the MMP-9 and COX-2 expression in TPA-induced breast cancer cells by inducing HO-1 expression

Oncology Reports ◽

10.3892/or.2013.2843 ◽

2013 ◽

Vol 31 (1) ◽

pp. 497-504 ◽

Cited By ~ 20

Author(s):

SUN YOUNG PARK ◽

MEI LING JIN ◽

YOUNG HUN KIM ◽

SANG-JOON LEE ◽

GEUNTAE PARK

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cox 2

Download Full-text

Increased Oxidative Stress Induced by Rubus Bioactive Compounds Induce Apoptotic Cell Death in Human Breast Cancer Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6797921 ◽

2019 ◽

Vol 2019 ◽

pp. 1-18 ◽

Cited By ~ 8

Author(s):

Blassan P. George ◽

Heidi Abrahamse

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Cell Death ◽

Cytochrome C ◽

Cancer Cells ◽

Bioactive Compounds ◽

Breast Cancer Cells ◽

Apoptotic Cell ◽

Ros Production ◽

Caspase 9

Bioactive compounds from plants represent good candidate drugs for the prevention and treatment of various forms of cancer. Berries are rich sources of bioactive compounds, and there has been an increasing interest in the study of therapeutic action of wild berries. Oxidants are generated continuously in biological system as a result of physiological process. When there is an imbalance between oxidants and antioxidants, it leads to a condition called oxidative stress. Natural compounds as inducers of oxidative stress are able to modulate the physiological functions of cancer cells leading to cell death or survival. The aim of this study was to evaluate the induction of apoptosis by isolated bioactive compounds (1-(2-hydroxyphenyl)-4-methylpentan-1-one (C1) and 2-[(3-methylbutoxy) carbonyl] benzoic acid (C2)) from Rubus fairholmianus against MCF-7 breast cancer cells. The exposure of C1 and C2 reduced viability (IC50 of C1: 4.69; C2: 8.36 μg/mL) and proliferation. Cytochrome c release from mitochondria and changes in mitochondrial membrane potential of treated cells supported the intrinsic apoptotic cell death. Reactive oxygen species (ROS) production after treatment with C1 and C2 was found to be higher and induced nuclear damage. Expression of apoptotic proteins after the treatments was significantly upregulated as indicated using immunofluorescence (caspase 9, p53, and Bax), western blotting (p53, cleaved PARP, cytochrome c, and Bax), and ELISA (caspase 9) analysis. Overall, C1 was more cytotoxic, increased the ROS production in dichlorodihydrofluorescein diacetate assay, and induced apoptosis in breast cancer cells. These results illustrate that berry bioactive compounds have strong chemopreventive potential. In this article, we provide information on prooxidant and anticancer activities of Rubus bioactive compounds. Natural products have always demonstrated a significant contribution to the development of several cancer chemotherapeutic drugs. Most of these compounds are known to affect the redox state of the cell; and studies on these compounds have focused on their antioxidant property instead of prooxidant properties.

Download Full-text

American Ginseng Inhibits Induced COX-2 and NFKB Activation in Breast Cancer Cells

Journal of Surgical Research ◽

10.1016/j.jss.2009.05.011 ◽

2009 ◽

Vol 157 (2) ◽

pp. 261-267 ◽

Cited By ~ 18

Author(s):

Elizabeth A. Peralta ◽

Laura L. Murphy ◽

James Minnis ◽

Somaja Louis ◽

Gary L. Dunnington

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

American Ginseng ◽

Nfkb Activation ◽

Cox 2

Download Full-text

Beta-ionone-inhibited proliferation of breast cancer cells by inhibited COX-2 activity

Archives of Toxicology ◽

10.1007/s00204-019-02550-2 ◽

2019 ◽

Vol 93 (10) ◽

pp. 2993-3003 ◽

Cited By ~ 4

Author(s):

Hong-Wei Dong ◽

Kai Wang ◽

Xiao-Xia Chang ◽

Fei-Fei Jin ◽

Qi Wang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cox 2

Download Full-text

COX-2 inhibitor nimesulide analogs are aromatase suppressors in breast cancer cells

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/j.jsbmb.2010.06.004 ◽

2010 ◽

Vol 122 (4) ◽

pp. 232-238 ◽

Cited By ~ 7

Author(s):

Bin Su ◽

Xiaohan Cai ◽

Yanyan Hong ◽

Shiuan Chen

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cox 2

Download Full-text

COX-2 Induces IL-11 Production in Human Breast Cancer Cells

Journal of Surgical Research ◽

10.1016/j.jss.2005.11.582 ◽

2006 ◽

Vol 131 (2) ◽

pp. 267-275 ◽

Cited By ~ 53

Author(s):

Balraj Singh ◽

Jacob A. Berry ◽

Angela Shoher ◽

Anthony Lucci

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Cox 2

Download Full-text

Effect of cyclooxygenase inhibition on CXCR3 ligand secretion in breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.27_suppl.45 ◽

2011 ◽

Vol 29 (27_suppl) ◽

pp. 45-45

Author(s):

H. Bronger ◽

S. Kraeft ◽

A. Stöckel ◽

A. Welk ◽

M. Kiechle ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Prostaglandin E ◽

Human Breast ◽

Cox Inhibitors ◽

Cxcr3 Ligand ◽

Ifn Γ ◽

Cox 2

45 Background: In murine cancer models, the two IFN-γ inducible chemokines CXCL9 and CXCL10, those bind to the common receptor CXCR3, recruit NK cells and tumor-suppressive lymphocytes into the tumor site and impair tumor growth and metastatic spread. In human breast cancer (BC), we and others have shown that high levels of CXCL9 mRNA correlate with favorable prognosis and the number of infiltrating lymphocytes. Raising the intratumoral level of CXCR3 ligands might therefore be a feasible way to enhance the infiltration by tumor-suppressive immune cells and to improve immune intervention in breast cancer. Inhibition of cyclooxygenases (COX) has been shown to inhibit tumor growth and metastases formation in a lymphocytic and IFN-γ dependent manner. We therefore tested whether COX inhibition induces CXCR3 ligand secretion from breast cancer cells. Methods: Human MCF-7 and MDA-MB 231 BC cells were stimulated with IFN-γ with or without prostaglandin E2 (PGE2) or COX inhibitors (indomethacin, aspirin, celecoxib). CXCL9 and CXCL10 release was measured by ELISA. COX-1 and COX-2 expression was measured in 45 BC samples and correlated with intratumoral CXCR3 ligand concentration. Results: Prostaglandin E2 inhibits CXCL10 and CXCL9 release from breast cancer cells. Aspirin and indomethacin enhance the INF-γ mediated secretion of these CXCR3 ligands by inhibition of endogenous cyclooxygenases. Celecoxib has this effect only at low concentrations, at higher concentrations is shows PGE2 agonistic effects. In human breast cancer samples, COX-2 overexpression inversely correlates with CXCR3 ligand concentration, which shows that the mechanism of PGE2 induced CXCL9/CXCL10 suppression might also be relevant in vivo. Conclusions: Suppressing endogenous PGE2 by cyclooxygenase inhibition increases CXCL9 and CXCL10 release from breast cancer cells and is therefore a feasible way to enhance the infiltration of breast tumors by tumor-suppressive lymphocytes. However, our results show that unselective COX inhibitors might be more suitable than the COX-2 specific celecoxib. Clinical trials are now warranted to clarify the mechanisms and therapeutic efficacy of COX inhibition in breast cancer.

Download Full-text