Rosemary has been serving many culinary and medicinal benefits for a very long time and it improves digestion, improves memory and prevents brain ageing. It is one of the well-known evergreen herbs known for making fragrant body perfumes. It belongs to the family 'Lamiaceae' which includes other herbs such as oregano, basil and lavender which are native to the Mediterranean region.
Various research studies consider Rosemary to be one of the effective chemo-preventive agents which can prevent cancer and age-related skin damage. Rosemary is known to be rich in a variety of polyphenolic compounds such as carnosol, carnosic acid and rosmarinic acid which are usually found in the extract of rosemary and show anti-cancer effects.
The two main ingredients found in rosemary are caffeic acid and rosmarinic acid which show anti-oxidant and anti-inflammatory properties and protect the body cells from damage by free radicals.
It is also highly rich in carnosol and vitamin E (alpha-tocopherol) which are identified to detoxify substances which begin the breast cancer process. Rosemary is widely rich in carnosic acid and carnosic acid is a derivative of carnosol which contains a lactone ring. Carnosol has many properties such as anti-inflammatory, antioxidant, antimicrobial and anticancer. Carnosol shows anti-inflammatory properties which have the potential to reduce leukotrienes, inhibit 5- lipoxygenase and inhibit the secretion of leukocyte elastase.
Mechanisms of Rosemary
Rosemary serves many properties such as anti-inflammatory, radical scavenging and anti-oxidative properties which makes it an ideal chemo-preventive agent to treat cancer. These properties of the Rosemary serve many biological activities such as multi-drug resistance, anti-breast cancer activity, ability to activate apoptosis and metastasis process.
(1.) Apoptosis
Apoptosis or programmed cell death is a genetically regulated process which plays a major role in preventing cancer and the ability of rosemary to activate the apoptotic pathway makes it an efficient chemo-preventive agent.
Rosmarinic acid could block cell cycle G-2 to inhibit the activity of prostate cancer cells PC3 and plays an antitumor role by regulating the signaling pathway and inducing apoptosis.
The Carnosic acid in the rosemary extract induces apoptosis in human renal cancer cells by regulating the increase of sub- diploid DNA content and cleavage of PARP apoptotic fluid activates various apoptotic molecules such as caspase - 3.
Rosmarinic acid inhibits the proliferation of prostate cancer cells in a concentration-dependent manner and inhibits the migration cells.
(2.) Anti-Breast cancer activity
Carnosol plays a crucial role in preventing the growth of breast cancer cells and thus shows anti-breast cancer activity.
It significantly increases the ratio of estrogen alpha and beta subtypes by preventing the proliferation of breast cancer cells.
Carnosol inhibits the proliferation and differentiation of breast cancer cells, on the other hand, rosmarinic acid induces apoptosis and reduces the migration of breast cancer cells.
(3.) Metastasis process
Metastasis is considered to be one of the main hallmarks of cancer and rosemary acts on the cancer cells by reducing the metastasis process.
Various metalloproteinases such as MMP-2, MMP-9 and the urokinase plasminogen activator (upA) can diminish various extracellular matrix (ECM) constituents which are the key promoters of metastasis.
Carnosic acid inhibits the migration of the cancer cells by decreasing the action of the proteases such as UPA and MMPs.
(4.) Multi-drug resistance
One of the major hurdles to effective cancer treatment is multi-drug resistance (or the development of resistance to multiple drugs with multiple targets ) and cancer cells can exhibit resistance more broadly to different drugs with different mechanisms of action.
Rosemary affects the activity of the human drug transporter P- glycoprotein (MDR1, ABCB1) and multidrug resistance protein (MRP1 and ABCC1) and Carnosic acid can show combined action with curcumin which is a natural substance with antineoplastic capacities.
In Acute Myeloid Leukaemia (AML), combined administration of curcumin and carnosic acid could lead to synergistic growth inhibitory action and an increase in apoptosis through both extrinsic and intrinsic pathways.
(5.) Free-radical scavenging properties
Free- radicals are the unstable molecules which take part in the chemical changes of our body which leads to the build-up of free radicals eventually leading to cancer hence it is important to scavenge free radicals to prevent the high risks of cancer.
The O- diphenol hydroxyl group present in the structure of rosmarinic acid can scavenge free radicals. Carnosic acid of the rosemary extract interacts with each component of the free radicals and while scavenging reactive oxygen it produces antioxidants.
Role of Rosemary in treating different kinds of cancer
1. Kidney Cancer
In kidney cancer cells, Carnosic acid stimulates programmed cell death through ROS- caused endoplasmic reticular stress and could also trigger an increase in apoptotic markers such as ATF4 and caspase 3.
Carnosic acid could also lead to an increase in TRAIL-mediated apoptosis in caki cells and other types of renal cell lines through a change in the endoplasmic reticulum stress-related proteins such as Bcl-2, COMP and OR5.
2. Cervical cancer
Essential oils found in Rosemary could trigger a reduction of cell growth in the human ovarian carcinoma cell line A2780 and an intense cytotoxic effect on various ovarian cancer cell lines such as SK-OV-3 and HO-8910. Rosemary essential oil could also block the development of HeLa cells.
3. Prostate Cancer
Rosemary is popularly known for its ability to treat prostate cancer by inhibiting the proliferation of cancer cells.
Carnosol is involved in inhibiting tumour cell proliferation and induces apoptosis in PC3 prostate cancer cells by activating the G2/M phase cell cycle arrest and targetting the adenosine monophosphate-activated protein kinase pathway.
Various molecular mechanisms of the apoptotic pathway are involved such as inhibition of caspases 8 and caspases 9 and the activation of caspases 3 and 7 which leads to the activation of apoptosis in prostate cancer cells.
(4.) Breast cancer
Carnosic acid inhibits the cell cycle at the G2 phase and causes ROS - dependent apoptosis (programmed cell death ) and at a non-cytotoxic level, it causes a low increase in ROS production and triggers autophagy (self-destructive process ).
Prolonged contact with high levels of carnosic acid causes excessive ROS generation which activates apoptosis of breast cancer cells through the stimulation of intrinsic and extrinsic apoptotic pathways. Supercritical fluid rosemary extract (SFRE) significantly increases the action of drugs such as tamoxifen, paclitaxel and trastuzumab.
In ER-negative human breast cancer cells, carnosic acid at a low dosage increases the expression of three genes involved in glutathione synthesis(CYP4F3, GCLC ) and transport (SLC7A11).