Celery is recommended for breast cancer
Celery (Apium graveolens) is an excellent dietary source of vitamin C and vitamin K, and also contains potassium, fiber, manganese, molybdenum and some B vitamins. Among vegetables, celery has relatively high sodium and nitrate levels, but the amounts are still low compared to those found in processed foods. Celery has been shown to have anti-inflammatory, antioxidant, antifungal, antimicrobial, and diuretic properties and can help lower cholesterol levels. Celery contains several substances with suspected or demonstrated cancer fighting properties, including apigenin, apiuman, luteolin, chrysoeriol, coumarin, and several polyacetylenes and phthalides. Celery seeds also contain perillyl alcohol, which has been found to have chemopreventive activity.Celery seed extracts have been shown to inhibit carcinogen-induced liver and stomach cancer in laboratory animals. Apigenin has been shown to induce apoptosis in human skin, thyroid, gastric, liver, colon, cervical, and prostate cancer cells, and to inhibit migration and invasion of ovarian cancer cells. Luteolin has been shown to induce apoptosis in oral cancer calls, to promote cell cycle arrest and apoptosis in colon cancer cells, and to inhibit insulin-like growth factor 1 receptor signaling in prostate cancer cells. Luteolin has also been shown increase the anti-cancer effects of the chemotherapy drug Taxol (paclitaxel). Celery consumption has been found to be associated with lower risks of lung, ovarian, gastric and colorectal cancers in population studies.
Breast cancer-related effects of eating celery
The flavone apigenin has been shown to exhibit potent growth-inhibitory effects in HER2/neu-overexpressing breast cancer cells; exposure of the HER2/neu overexpressing breast cancer cells to apigenin results in induction of apoptosis by depleting HER2/neu protein. The growth-inhibitory effects of apigenin are less powerful for those cells expressing normal levels of HER2/neu. Apigenin has also been shown to act both as an estrogen and as an anti-estrogen, depending on the dose, promoting estrogen-dependent breast cancer cell growth at low dosages. Perillyl alcohol has been shown to inhibit both ER+ and ER- human breast cancer cell growth and suppress growth and metastasis in a nude mouse model.
Celery has been shown to have a modest ability to inhibit aromatase (the synthesis of estrogen from androgens within the body), which is important for reducing growth-stimulatory effects in estrogen-dependent breast cancer. A major Italian population study including 2,569 women with breast cancer found that the risk of breast cancer was reduced for increasing intake of flavones such as apigenin and luteolin in the diet.
Additional comments
Like carrots, parsnips, fennel, dill and parsley, celery is an apiaceous or umbelliferae vegetable. Non-organic celery must be washed very thoroughly to remove pesticide residue as much as possible. The tender innermost stalks of a celery plant are called the celery heart. Celery seed spice can be high in sodium. Celery root (Apium graveolens Rapaceum Group), also called celeriac, is an edible root vegetable closely related to celery. The stalks and leaves of celery root generally are not eaten because of their unpleasant taste, however, the celery root tuber has an excellent flavor. Celery root contains falcarinol, which has been shown to have toxicity against acute lymphoblastic leukemia cells.
We do not recommend taking apigenin, luteolin, perillyl alcohol or celery seed extract supplements. None of these have been demonstrated to be safe and effective; in fact, apigenin may promote breast cancer growth in some circumstances.
Women who are pregnant or nursing should not take celery seed since it can stimulate the uterus.
Selected studies
Apigenin inhibits antiestrogen-resistant breast cancer cell growth through estrogen receptor--dependent and estrogen receptor--independent mechanisms Molecular Cancer Therapeutics, July 2008Breast cancer resistance to the antiestrogens tamoxifen and fulvestrant (Faslodex) has been found to be accompanied by changes in both estrogen-dependent and estrogen-independent signaling pathways. Therefore, effective inhibition of both pathways may be necessary to block proliferation of tamoxifen- or fulvestrant-resistant breast cancer cells. The current study examined the effects of apigenin, a dietary plant flavonoid, on estrogen receptor positive MCF7 human breast cancer cells and two MCF7 sublines with acquired resistance to either tamoxifen or fulvestrant. It was found that apigenin can act as both an estrogen and as an antiestrogen in a dose-dependent manner. At low concentrations (1 µmol/L), apigenin promoted MCF7 cell growth but had no effect on the growth of the antiestrogen-resistant MCF7 sublines. At high concentrations (>10 µmol/L), apigenin inhibited growth of both regular MCF7 cells and the antiestrogen-resistant sublines. Furthermore, the combination of apigenin with either tamoxifen or fulvestrant demonstrated synergistic growth-inhibitory effects on both antiestrogen-sensitive and antiestrogen-resistant breast cancer cells. This authors conclude that apigenin holds promise as a new therapeutic agent against antiestrogen-resistant breast cancer.
Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and β4 integrin function in MDA-MB-231 breast cancer cells Toxicology and Applied Pharmacology, January 2008
Hepatocyte growth factor and its receptor, Met, are known to play crucial roles in promoting breast cancer metastasis and some dietary flavonoids are known to suppress their effects. However the pharmacological and molecular mechanisms are poorly understood. In the current study, the effect of the flavonoids apigenin, naringenin, genistein and kaempferol on hepatocyte growth factor-dependent invasive growth of MDA-MB-231 human breast cancer cells was evaluated. Apigenin was found to have the most potent anti-migration and anti-invasion properties. In addition to its effect on breast cancer cells, apigenin was found to have inhibitory effects on hepatocyte growth factor-induced Akt phosphorylation in liver and lung cancer cells.
Stimulatory effect of genistein and apigenin on the growth of breast cancer cells correlates with their ability to activate ER alpha Breast Cancer Research and Treatment, September 2006
The current study was designed to assess the influence of the phytoestrogens genistein and apigenin on breast cancer growth. Genistein and apigenin are present in several commercial supplements designed to be used for postmenopausal symptoms and breast health. Both flavonoids were found to stimulate proliferation of estrogen receptor-positive/progesterone receptor-positive (ER+/PR+) MCF-7 and estrogen receptor alpha (ERα-positive) T47D breast cancer cells. However, the compounds did not stimulate the proliferation of ERα-negative MDA-MB-435 breast cancer cells. Genistein was observed to be more efficient in this regard due to its higher binding affinity for ERα. Similarly to actions previously described for estradiol (E2), both genistein and apigenin were found to down regulate ERα and enhance estrogen response element-dependent gene expression. An additional finding that genistein antagonizes the anti-proliferative effect of hydroxytamoxifen indicates that certain phytoestrogens may be detrimental for women with breast cancer who are being treated with tamoxifen. The authors conclude that because of their ability to stimulate breast cell growth, the use of phytoestrogen supplements in postmenopausal women could be detrimental.
Flavonoids and Breast Cancer Risk in Italy Cancer Epidemiology, Biomarkers & Prevention, April 2005
The present study investigated the potential relationship between flavonoid consumption and risk of breast cancer. Dietary information was collected in a large study conducted in Italy between 1991 and 1994, including 2,569 women with breast cancer and 2,588 hospital controls. After allowing for major confounding factors and energy intake, risk of breast cancer was found to be reduced for increasing intake of flavones (e.g., apigenin, luteolin, tangeritin) and flavonols (e.g., fisetin, quercetin, myricetin, kaempferol). No significant association was found for other flavonoids, including flavanones, flavan-3-ols, anthocyanidins, as well as for isoflavones. These findings confirm the results of a previous Greek study.
Perillyl Alcohol Inhibits Human Breast Cancer Cell Growth in vitro and in vivo Breast Cancer Research and Treatment, April 2004
The present study was designed to examine the effect of monoterpene perillyl alcohol on cell growth, cell cycle progression, and expression of cell cycle-regulatory proteins in human breast cancer cells. Estrogen receptor positive (ER+) MCF-7 and KPL-1 cells and estrogen receptor negative (ER-) MDA-MB-231 and MKL-F cells were used in the study. Perillyl alcohol was found to inhibit cell proliferation in all of the cell lines tested in a dose-dependent manner. At a dose of 500 µM, perillyl alcohol was shown to have a cytostatic effect, in which growth inhibition was due to accumulation of cells in G1-phase. Levels of p53 and cyclin A appeared to be unchanged. Further experiments were conducted using nude mice with orthotopically transplanted KPL-1 tumor cells. Perillyl alcohol at a dose of 75 mg/kg was administered intraperitoneally three times per week throughout a six week experimental period. This dose was found to suppress KPL-1 tumor cell growth and regional lymph node metastasis. The authors conclude that perillyl alcohol inhibited both ER+ and ER- human breast cancer cell growth in vitro, and suppressed growth and metastasis in vivo.
Apigenin Induces Apoptosis through Proteasomal Degradation of HER2/neu in HER2/neu-overexpressing Breast Cancer Cells via the Phosphatidylinositol 3-Kinase/Akt-dependent Pathway Journal of Biological Chemistry, November 2003
Apigenin, a common flavonoid, is found in many fruits and vegetables, including Chinese cabbage, bell pepper, garlic, celery and guava. Although some flavonoids are mutagenic, apigenin has been found to have no mutagenic activity and, in fact, apigenin exhibits anti-proliferative activity against human breast cancer cells. In the present study, apigenin activity in human breast cancer cell lines having different levels of HER2/neu expressions was examined. It was found that apigenin exhibited potent growth-inhibitory effects in HER2/neu-overexpressing breast cancer cells but was much less powerful for those cells expressing basal levels of HER2/neu. Proapoptic activity was also observed in HER2/neu-overexpressing cells in a dose- and time-dependent manner. A cell survival pathway involving phosphatidylinositol 3-kinase and Akt is known to play a significant role in preventing apoptosis in HER2/neu-overexpressing breast cancer cells. The study results found that apigenin inhibits Akt function in tumor cells in a complex manner.
