Apigenin Acts on the Tumor Cell Invasion Process and Regulates Protease Production

Lindenmeyer, F.; Li, H.; Ménashi, Suzanne; Soria, Claudine; Lű, He

doi:10.1207/s15327914nc391_19

Cited by 97 publications

(60 citation statements)

References 36 publications

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“…Our results show that apigenin, even though no effect on the expression level and basal secretion of MMP-9, totally abolished the response to PMA stimulation in those cancer cells. Our results are in agreement with the observations that apigenin blocked PMAinduced up-regulation of MMP-9 secretion in MDA-231 breast cancer cells (25). However, they reported that apigenin treatment caused a remarkable decrease at the mRNA and protein levels of urokinase plasminogen activator (u-PA), we failed to detect significant changes in u-PA mRNA expression level in Caski, MDA-231, and SK-Hep1 cell lines (data not shown).…”

Section: Discussionsupporting

confidence: 93%

“…Several studies have identified signal transduction pathways such as ERK and p38 MAPK signaling pathways which were involved in regulation of MMP-2 and MMP-9 expression in malignant cells (25)(26)(27)(28). In our system, PMAinduced MMP-9 expression was strongly attenuated by ERK inhibitor PD98059 or p38 inhibitor SB203580 treatment in Caski cells.…”

Section: Discussionmentioning

confidence: 81%

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Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by apigenin via the inhibition of p38 mitogen-activated protein kinase-dependent matrix metalloproteinase-9 expression

Lee¹

2010

Oncol Rep

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Abstract. Apigenin has special interest for the development of chemopreventive agents against cancer because it is a widely distributed plant flavonoid that has antitumor properties. In this study, we investigated the apigenin effects on the protease-mediated invasiveness in human metastatic cancer cell lines Caski, SK-Hep1, and MDA-231. We found that apigenin markedly inhibits the phorbol-12-myristate-13-acetate (PMA)-induced increase in MMP-9 expression and activity in several cancer cell lines. These effects of apigenin are dose-dependent and correlate with the suppression of MMP-9 mRNA expression levels. PMA caused about a 5-fold induction in MMP-9 promoter activity, which was also suppressed by apigenin treatment in Caski cells. We found that apigenin could inhibit PMA-induced phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), which was involved in the down-regulation of the expression of matrix metalloproteinase-9 (MMP-9) at mRNA levels. Furthermore, the treatment of inhibitors specific for p38 MAPK (SB203580) to Caski cells caused the reduction of MMP-9 expression. Restoration of p38 expression partly increased PMA-induced MMP-9 secretion blocked by apigenin treatment in Caski cells. These results showed apigenin might inhibit the invasion and migration abilities of Caski cells by reducing the MMP-9 expression through suppressing the p38 MAPK signaling pathway. These findings indicate that apigenin might be a useful strategy for controlling metastasis and the invasiveness of tumors.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 81%

Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by apigenin via the inhibition of p38 mitogen-activated protein kinase-dependent matrix metalloproteinase-9 expression

Lee¹

2010

Oncol Rep

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“…Apigenin has shown promise in inhibiting tumor cell invasion and metastases by regulating protease production (57). Apigenin under in vivo conditions is also effective in inhibiting TNF·-induced intracellular adhesion molecule-1 up-regulation in cultured human endothelial cells (58).…”

Section: Achillea Millefoliummentioning

confidence: 99%

“…Lindenmeyer et al (57) demonstrated the effect of apigenin on protease-mediated invasiveness in estrogen-insensitive breast tumor cell line MDA-MB231, showing that apigenin strongly inhibited tumor cell invasion in a dose-dependent manner. Apigenin inhibits growth and induces G2/M arrest by modulating cyclin-CDK regulators and ERK MAP kinase activation in breast carcinoma cells (80).…”

Section: Apigenin and Cancermentioning

confidence: 99%

Apigenin and cancer chemoprevention: Progress, potential and promise (Review)

Patel

Shukla²,

Gupta³

2007

Int J Oncol

311

362

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Abstract. Cancer is one of the major public health burdens in the United States and in other developed countries, causing approximately 7 million deaths every year worldwide. Cancer rates vary dramatically in different regions and populations around the globe, especially between developing and developed nations. Changes in cancer prevalence patterns occur within regions as their populations age or become progressively urbanized. Migration has also contributed to such variations as changes in dietary habits influence cancer rates. These epidemiologic findings strongly suggest that cancer rates are influenced by environmental factors including diet, which is largely preventable. Approaches to prevent cancer include overlapping strategies viz. chemoprevention or dietary cancer prevention. Chemoprevention aims at prevention or reversal of the initiation phase of carcinogenesis or arrest at progression of carcinogenesis through the administration of naturally occurring constituents or pharmacological agents. Cancer prevention through diet may be largely achievable by increased consumption of fruits and vegetables. Considerable attention has been devoted to identifying plant-derived dietary agents which could be developed as promising chemopreventives. One such agent is apigenin. A naturally occurring plant flavone (4', 5, 7,-trihydroxyflavone) abundantly present in common fruits and vegetables including parsley, onions, oranges, tea, chamomile, wheat sprouts and some seasonings. Apigenin has been shown to possess remarkable anti-inflammatory, antioxidant and anti-carcinogenic properties. In the last few years, significant progress has been made in studying the biological effects of apigenin at cellular and molecular levels. This review examines the cancer chemopreventive effects of apigenin in an organ-specificity format, evaluating its limitations and its considerable potential for development as a cancer chemopreventive agent.

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“…Studies of human malignant cancer cell lines have shown that apigenin inhibits cancer cell growth via the promotion of cell cycle arrest and apoptosis (8,9). As a candidate anticancer agent, apigenin is of particular interest because it exhibits selective induction of cell cycle arrest and apoptosis in human prostate carcinoma cells without affecting normal cells (10,11).…”

Section: Introductionmentioning

confidence: 99%

5-Fluorouracil combined with apigenin enhances anticancer activity through induction of apoptosis in human breast cancer MDA-MB-453 cells

Choi

Kim²

2009

Oncol Rep

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Abstract. We investigated the effects of combined treatment with 5-fluorouracil and apigenin on proliferation and apoptosis, as well as the underlying mechanism, in human breast cancer MDA-MB-453 cells. The MDA-MB-453 cells, which have been shown to overexpress ErbB2, were resistant to 5-fluorouracil; 5-fluorouracil exhibited a small dose-dependent anti-proliferative effect, with an IC 50 of 90 μM. Interestingly, combined treatment with apigenin significantly decreased the resistance. Cellular proliferation was significantly inhibited in cells exposed to 5-fluorouracil at its IC 50 and apigenin (5, 10, 50 and 100 μM), compared with proliferation in cells exposed to 5-fluorouracil alone. This inhibition in turn led to apoptosis, as evidenced by an increased number of apoptotic cells and the activation of caspase-3. To investigate the mechanism by which the combination of 5-fluorouracil and apigenin induces apoptosis, ErbB2 expression was analyzed. The level of ErbB2 was unchanged by 5-fluorouracil alone but was drastically reduced in cells treated with 5-fluorouracil plus apigenin. Moreover, compared with 5-fluorouracil alone, 5-fluorouracil in combination with apigenin at concentrations >10 μM exerted a pro-apoptotic effect via the inhibition of Akt expression. Taken together, our results suggest that 5-fluorouracil acts synergistically with apigenin inhibiting cell growth and inducing apoptosis via the down-regulation of ErbB2 expression and Akt signaling.

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Apigenin Acts on the Tumor Cell Invasion Process and Regulates Protease Production

Cited by 97 publications

References 36 publications

Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by apigenin via the inhibition of p38 mitogen-activated protein kinase-dependent matrix metalloproteinase-9 expression

Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by apigenin via the inhibition of p38 mitogen-activated protein kinase-dependent matrix metalloproteinase-9 expression

Apigenin and cancer chemoprevention: Progress, potential and promise (Review)

5-Fluorouracil combined with apigenin enhances anticancer activity through induction of apoptosis in human breast cancer MDA-MB-453 cells

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