Rosemary (Rosmarinus officinalis L.) is a plant of the Lamiaceae family, which originates from the Mediterranean area. Over the past decades, experimental research has confirmed the pharmacological potential of rosemary and some of its primary compounds like diterpenes, carnosic acid and carnosol. The antitumor potential of rosemary extracts and its main polyphenols (carnosic acid, carnosol, rosmarinic acid, rosmanol, methyl carnosate and betulinic acid, among others) has been studied in vitro and in vivo.
Numerous studies reported that rosemary extracts exhibit chemoprotective effects against hepatotoxicity and gastric ulcerative lesions, as well as anticancer, antimicrobial, antioxidant and antidiabetic effects, both in vitro and in vivo. Data suggest that diterpenes are the most effective molecules against neoplastic growth, followed by triterpenoids, which have shown minor efficacy.
The antitumor potential of rosemary extracts has been linked to different mechanisms. These mechanisms include antioxidant effect, antiangiogenic properties, epigenetic actions, regulation of the immune response, alteration of hormone signaling, modification of specific metabolic pathways, and increased expression of onco-suppressor genes.
Rosemary has been primarily recognized as a possible anticancer drug primarily due to its antioxidant activity. It has the ability to act on free radicals, and can defend DNA, proteins, and lipids from the oxidative damage of free radicals. However, the rosemary derivatives are, under certain conditions, able of inducing a cytotoxic effect through the release of reactive oxygen species.
In addition to its scavenging action, rosemary extracts have been found to control intracellular antioxidant systems. Transcriptomic and metabolomic analysis in colon cancer cells indicated that treatment with rosemary extracts activated the expression of genes related to cell cycle progression and phase II antioxidant enzymes.
Rosemary and its derivatives are also known to stimulate the innate immune response due to the increased activity of natural killer cells. They also create an anti-inflammatory cytokine profile that could support the immune response to malignant cells.
About the studies
An extensive review article from Allegra A, et al. discussed the antitumor effect of rosemary and its possible use in the treatment of various neoplastic diseases. The scientists analyzed the results of preclinical studies on the anticancer effects of rosemary, the molecular mechanisms associated with these actions, and the interactions between rosemary and anticancer drugs.
According to the authors, rosemary produces its actions by stopping the activation of carcinogens, increasing antioxidant enzyme activities, reducing tumor-stimulating inflammation, decreasing cell growth, stimulating programmed cell death, and suppressing tumor angiogenesis and invasion.
The authors also analyzed the antitumor potential of rosemary derivatives in the treatment of various neoplastic diseases, including colon, gastric, esophageal, hepatocellular and pancreatic cancer, lung cancer, cerebral neoplasms, ovary, cervical and breast cancer, cutaneous neoplasms, kidney and prostate cancer, and hematological neoplasms. They also discussed the influence of rosemary to the metastatic process, as well as the possible synergistic effects between rosemary derivatives and chemotherapeutic agents.
Finally, the authors concluded that medicine is still far from being able to use rosemary and its derivatives in clinical practice, due to significant unresolved problems. It is essential to standardize the extraction system in order to obtain rosemary extracts with the same antiproliferative capabilities. Finally, further research is necessary to explore possible toxicity of the chronic administration of rosemary extracts, as well as a potential synergistic effect of rosemary derivatives with chemotherapeutic agents.
This review was published in Nutrients. Allegra A, et al. Anticancer Activity of Rosmarinus officinalis L.: Mechanisms of Action and Therapeutic Potentials. Nutrients 2020, 12, 1739; doi:10.3390/nu12061739 (Open Access) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352773/
The study of Pérez-Sánchez A, et al investigated the antitumor potential of rosemary extracts in vitro and in vivo. They assessed in vitro antiproliferative activity of rosemary extracts in three different colon cancer cell lines. They also evaluated in vivo effect of rosemary extracts on cancer progression in a mouse xenograft model of HT-29 colon cancer cells.
The results showed that rosemary extracts in vitro strongly inhibited proliferation, migration and colony formation of colon cancer cells. Cancer cell treatment with rosemary extracts resulted in an increase of intracellular reactive oxygen species, necrosis and cell death.
In vivo results demonstrated a reduction in tumor growth in a mouse xenograft model of colon cancer cells. Oral pretreatment with rosemary extracts for two weeks prior to cell inoculation appeared to be more effective than just the treatment itself.
The scientists concluded that controlled studies are needed to definitively clarify the real impact of rosemary extracts in clinical practice.
This study was published in Scientific Reports. Pérez-Sánchez A et al. Rosemary (Rosmarinus officinalis) extract causes ROS-induced necrotic cell death and inhibits tumor growth in vivo. Scientific Reports (2019) 9:808 | DOI:10.1038/s41598-018-37173-7 (Open Access) https://www.nature.com/articles/s41598-018-37173-7