Millions of women routinely receive hormone replacement therapy (HRT) to treat the myriad of symptoms associated with menopause. HRT formulations contain either estrogen (synthetic estrogen-like compounds) alone or a combination of estrogens and progestins (synthetic progesterone like compounds). The use of combination HRT (estrogen + progestin) has been linked to the rapid onset of a certain type of progestin-dependent breast cancer tumor. Research by a team of scientists from the University of Missouri, shows that apigenin, a flavinoid found in many common foods, especially celery and parsley, reduces breast cancer tumor growth in mice.
Progestin Dependent Breast Cancer Tumors
Medroxyprogesterone acetate (MPA), a progestin derived from testosterone used in HRT and several oral contraceptives, is associated with an increased risk of breast cancer and an increased growth rate of a particular type of tumor, the HER2/neu-positive. The HER2 cancers are typically very aggressive and difficult to treat.
Researchers believe MPA stimulates cancer cell growth by:
- Inducing the expression of vascular endothelial growth factor (VEGF), a potent pro-angiogenic factor in breast cancer cells. (Angiogenesis means the growth of new blood vessels. Tumors need a blood supply to survive.)
- Activating several genes that increase cell motility (movement) and the rate of cancer metastasis
- Inducing receptor activation of nuclear factor kappa-B ligand (RANKL) – higher RANKL may correlate with higher rates of mammary cancer in mice
Apigenin and Breast Cancer Tumors: The Research
For the current study, researchers investigated the effect apigenin, which is ubiquitous in fruits, nuts, vegetables, and plant-derived beverages, on the progression and development of MPA-dependent BT-474 xenograft tumors (HER2/Neu-positive) in nude mice (lab mice without a thymus that cannot mount an effective immune responses). They found that apigenin (21 daily 50 mg/kg subcutaneous injections) significantly inhibited the growth of BT-474 xenograft tumors. Cancerous tumors grew rapidly in the mice which did not receive apigenin. In the apigenin-treated mice, breast cancer cell growth dropped to that of the control group, and the tumors shrank.
Apigenin is an natural component that humans and animals consume already. In the dosage used for this and other studies, no side effects were observed. By virtue of its ability to selectively induce apoptosis (cell death) in rapidly growing breast cancer cells, while having no effect on normal breast cells, apigenin would seem to be an extremely useful cancer treatment.
Apigenin may also reduce the production by tumor cells of pro-angiogenic VEGF, which is essential for growth and maintenance of blood vessels in the tumor. The potential use of a natural antiprogestin would therefore appear to possess a number of advantages. Authors suggest exploring the combined use of apigenin and tamoxifen or aromatase inhibitors. They would also want to examine the effects of apigenin on breast cancer progression promoted by other synthetic progestins and the endogenous hormone progesterone.
Although much research remains, early indicators suggest that apigenin may be a promising new therapeutic option for certain cancers.