Artemisinin selectively reduces estrogen receptor-alpha functional levels and eliminates estrogen-induced proliferation in human breast cancer cells.
Breast cancer continues to persecute women as the second leading cause of death. His terror remains unstoppable even with the advanced medical knowledge of our century. In the United States alone, one in eight women will be diagnosed with breast cancer some time during her lifetime. It is estimated that 220,000 women in the United States will be diagnosed with breast cancer each year, of which 40,000 will die.
Breast cancer, like other cancers, results from a complex interaction between external and internal factors. The list of external factors includes inactive (sedentary) lifestyles, night shifts, exposure to alcohol and tobacco, etc. Internal factors are genetic makeup, lifestyle, and among them, the most important factors are being a woman and old age. Breast tissue becomes cancer when it loses the ability to stop dividing, remain attached to neighboring cells, and die at a programmed time. Several factors have been investigated as a cause of cancer; an inherited genetic mutation is the primary cause of suspicion. However, studies have found that only in 5-10% of patients with breast cancer can hereditary genetic mutations qualify as the cause of cancer. BRCA genetic mutations are the best known. Familial relationship was observed in several cases with a risk factor ranging from 7.8 to 21.1%, and the highest risk of breast cancer among them has a first-degree relative. However, regardless of the above, the biggest risk factors remain women and the elderly.
The prognosis of breast cancer depends on many factors. Therapeutic modalities, however, may be reduced to the central role of estrogen. Thus, breast cancer falls into two categories: estrogen-sensitive and estrogen insensitive. Studies indicate that breast cancer cells have two main estrogen receptors, ERα and ERβ. These receptors’ size determines cancer’s malignant behavior and its therapeutic modalities, and then the prognosis. A higher ERα: ERβ ratio is correlated with higher cell proliferation, while a lower ERα: ERβ ratio is correlated with the anti-proliferative state.
Most breast cancers with ERα are sensitive to estrogen, and treatment modalities for these types of breast cancer include taking anti-estrogen drugs such as Tamoxifen and Fulvestrant. These drugs work by blocking estrogen receptors, and as a result, suppress the proliferative behavior of cancer cells. On the other hand, estrogen-insensitive breast cancer is usually treated with surgical removal of breast tissue, followed by general chemotherapy. Estrogen-sensitive breast cancer provides a better prognosis since anti-estrogen drugs can be taken. However, long-term use of these drugs does not pass without side effects. Side effects include an increased risk of endometrial cancer and an increased chance of developing DVT (deep vein thrombosis).
Since there is detailed pharmacological profiling of current anti-estrogen drugs, attention has been paid to the research of drugs with side effects that are more easily tolerated. The sweet wormwood extract, Artemisinin, has been significantly considered among the candidates due to its anti-cancer effects. Artemisinin, a sesquiterpene lactone, is extracted from the Chinese plant Artemisia annua, better known as qinghaosu or sweet wormwood. It bears with its name a millennium-long history of the wide medical application by the Chinese, most often for the treatment of fever. In the late 1990s, Novartis filed a patent to provide an anti-malarial drug based on Artemisinin with unusual results. The study of its anti-malarial effects and properties leads to another promising anti-cancer effect of Sweet Wormwood Artemisinin.
The anti-cancer mechanism of artemisinin is currently intensively investigated; Several pieces of evidence have supported the formulation of a model in which Sweet Wormwood Artemisinin extract kills cancer cells by causing irreparable damage through ROS (reactive oxygen species) by targeting high-iron cancer cells. It also induces apoptosis in cancer cells, forcing mutated cells to commit programmed suicide. The Developmental Therapeutics Program of the National Cancer Institute, USA, analyzes the effects of Artemisinin on 55 human cancer lines and demonstrates anti-cancer activity against several types of cancer, including leukemia, colon cancer lines, melanoma, and breast, ovarian, prostate, and central cancer lines. The nervous system as well as the kidneys. Earlier studies have also elucidated its effect against angiogenesis and its effect on cell arrest, and it, therefore, prevents the proliferation and metastasis of cancer cells.
Artemisinin affects breast cancer
Researchers have also proven in previous studies that Artemisinin affects breast cancer when it comes to breast cancer. In a 2008 study by Sunder et al., treatment of MCF7 cells (a line of human estrogen-responsive human breast cancer cells expressing both alpha (ERα) and beta (ERβ) estrogen receptors) with artemisinin, a phytochemical from Sweet Wormwood, effectively blocked the progression of estrogen-stimulated cells. Artemisinin has been shown to regulate and reduce the ERα protein and its transcripts with very little to no regulatory effect on ERβ, restoring the high ERα: ERβ ratio to a level close to physiological levels.
An earlier study conducted by Lai and Singh in 2006 on rats states the potential activity of Artemisinin on breast cancer cells. Rats exposed to a potent breast carcinogen, 7,12-dimethylbenz (a) atrazine (DMBA), were given oral Artemisinin. The results reflect the inhibition of breast cancer. Since these cancer cells are sensitive to estrogen, the result is thus extrapolated to a possible mechanism by which Artemisinin disrupts estrogen promotion in the rat breast epithelium, presumably by interference through ERα activity.
Translating a study on human cancer cells, Sundar et al. found that Artemisinin reduces ERα promoters, reducing its transcription and keeping its levels low. Artemisinin treatment also reverses the induction of endogenous progesterone receptor transcripts via E2 or PPT and inhibits estrogenic stimulation of estrogen-responsive (ERE) compliant plasmid-induced luciferase. Chromatin immunoprecipitation tests showed that Artemisinin extensively reduced ERα binding to the progesterone receptor promoter, while the level of ERβ binding remained unchanged. The results translate into a low proliferation state after treatment with Artemisinin, a condition normally seen in human breast epithelial cells.
There is a strong recommendation for Artemisinin as adjunctive therapy along with current anti-estrogen therapy with these results. The combination promises positive synergy with promising significantly lower side effects of anti-estrogen therapy. In long-term anti-estrogen therapy of patients with estrogen-sensitive breast cancer, the combination with the naturally occurring phytochemicals Sweet Wormwood, Artemisinin, will benefit patients to reduce systemic exposure to anti-estrogen side effects.