A natural plant compound called sanguinarine has shown promising anti-cancer effects against cell lines from triple-negative breast cancer patients, according to research from Florida A&M University in Tallahassee. The study also found that breast cancer cell lines from African-American women were significantly more sensitive to the natural compound than Caucasian-American women.
"In cancer therapy, finding a novel drug with the potential to induce cell cycle arrest and apoptosis is being substantially pursued," said Samia S. Messeha, PhD, MPH, a research associate at Florida A&M, who presented the study's findings at the American Society for Investigative Pathology annual meeting during the virtual Experimental Biology 2021 meeting. "This compound exhibits both apoptosis and cell cycle arrest in various types of cancer, including breast cancer," she added.
About 15-20 percent of breast cancers are triple-negative, which means the cancer lacks-or is negative for-receptors for estrogen or progesterone and doesn't make excess amounts of protein called HER2. The absence of hormone receptors means these tumors do not respond to hormone-based therapies used for other types of breast cancer. Current treatments therefore are limited to surgery, radiation, and chemotherapy. For this reason, researchers and clinicians are seeking new therapeutic strategies to fight this type of cancer.
Triple-negative breast cancer is particularly aggressive in African-American women, with a mortality rate about 42 percent higher than Caucasian-American women, owing to both biological and socioeconomic factors, according to epidemiological studies. What's more, African-American women are 2-3 times more likely to develop this type of breast cancer than women of European descent.
"Treatment regimens for breast cancer have greatly improved," Messeha noted in an interview. "However, the emergence of new subtypes of the disease requires the development of a new therapy for treating these aggressive types of cancer.
"Natural products have been and continue to be a great source of pharmacologically effective compounds with a superior capability in treating various types of disease, including the aggressive subtype of breast cancer," she added.
Sanguinarine or SAN, found in bloodroot among other medicinal plants, has shown a broad range of pharmacological activities, including antibacterial, antioxidant, anti-inflammatory, antidepressant, and antiplatelet effects. In previous studies, the compound also has shown promising anticancer effects, including inhibition of tumor initiation, development, and metastasis, across a spectrum of cancer types.
Study Details
For this study, Messeha and colleagues tested SAN against two genetically different triple-negative breast cancer cell models, one from African-American women and the other of Caucasian-American origin.
In a series of assays to test for cytotoxicity and rate of growth or proliferation, the researchers found that short-term (24 hours) and long-term (48-96 hours) exposure to SAN decreased cell viability and proliferation in both cell lines. "SAN induced apoptosis in both cell lines by arresting cell growth," Messeha said.
However, the two cell lines responded to the compound in different ways. Results were dose-dependent, but cells from African-American women were 2.5-fold more sensitive to the compound than its counterpart from Caucasian-American women.
Surprisingly, the cytotoxic effect of the compound was about the same as the commonly used chemotherapeutic agent doxorubicin after 72 hours of exposure, Messeha noted.
Following their cytotoxic and antiproliferation tests, the Florida A&M researchers isolated the different genes mutated to orchestrate apoptosis. In the cell line from African-American women, about 18 genes were significantly upregulated in the presence of the compound. In the cell line from Caucasian-American women, five genes were significantly upregulated when exposed to SAN, with seven others down-regulated.
"These results provide evidence that genetically different cells may respond differently to treatments, explaining the inadequate therapeutic response of some patients with advanced triple-negative breast cancer," the researchers said in an abstract of their study.
"Our findings are consistent with those previously mentioned by others," Messeha added. "The compound showed a potent effect on cell viability. It decreased the proliferation rate and its ability to alter the expression of various genes mediating programmed cell death."
Though encouraging, Messeha conceded the promise of SAN in the clinical setting is controversial owing, in part, to epidemiological studies suggesting the compound may be linked to oral leukoplakia when used in dental hygiene products including toothpaste and mouthwashes to reduce plaque.
"However, this compound was found safe in normal cells and various studies are interested in changes of the chemical structure of this compound, with some modifications to optimize the dose so it will be safe when we apply to breast cancer or triple-negative breast cancer patients," she added.
As for next steps, Messeha said her team will continue to investigate the potential of this compound by itself and in combination with other drugs used to treat breast cancer.
The findings obtained from this investigation should guide the prospective utilization of sanguinarine as an adjunct therapy for breast cancer cells-with aggressive nature-to increase chemotherapy effectiveness and prevent cancer metastasis," said Messeha
"Still, we need to investigate the effect of sanguinarine in non-cancerous cells and in vitro models," she added.
Warren Froelich is a contributing writer.