Cancer as we all know is one among many diseases which brings about discomfort to both the patients and their caretakers. India exhibits heterogeneity in cancer. Lung, mouth, esophagus, stomach, and nasopharynx cancers are the most common cancers in men. Cancer of the breast and the cervix uteri are the most common cancers in women. Traditional methods for treatment which are already available involve chemotherapy, radiation therapy, gene therapy etc. The recovery rate or the prognosis of cancer is not 100% or up to the level of satisfaction all over the globe. In order to tackle this issue at hand so as to increase the quality of life of the patient undergoing prognosis, it is always beneficial to add on to the existing treatment. In this aspect some of the Ayurvedic ingredients play a major role as the components present within these ingredients have the property of suppressing the tumors in one or the other way. Some of the Ayurvedic ingredients include Indian foods and spices which have been used from time immemorial. These also have proven to have some anticancer properties hence consuming the same along with the traditional methods of treatment on a regular basis con lead to better and satisfactory results. In this blog let us look at some of the properties of cumin locally known as jeera or jeeriga.
Cumin, a very well-known spice in Indian kitchen is a spice that comes from the Cuminum cyminum plant. It is native to Asia, Africa, and Europe. However, people all around the world use it to flavor meals. Although cumin seeds are widely used as a spice for their distinctive aroma, they are also commonly used in traditional medicine to treat a variety of diseases. Cumin can be put to use in battling cancer. It might not be as effective as the medicines available for the treatment of cancers but it definitely can help on a smaller scale.
Cumin has been reported to have components named Cuminaldehyde, cymene, and terpenoids. They are nutritionally rich as they provide high amounts of fat (especially monounsaturated fat), protein, and dietary fiber along with considerable amount of Vitamins B and E and several dietary minerals, especially iron. Cumin has a distinctive strong flavor. Its essential oil contents (cuminaldehyde and cuminic alcohol) give it a warm aroma.
In this blog we will be focusing on one of the many properties of cumin, namely - Chemo preventive effects:
A study suggested that cumin by reducing the production of nitrogenous compounds act as nutraceuticals and possess properties that have a protective effect against cancer and induction of oxidative pressure. Inflammation and neurological disorders were shown to be 80% protected. It was observed that Cumin increased the effectiveness of chemotherapy by increasing the sensitivity of specific drugs working against cancer cells. Nutraceutical potential in terms of antioxidant, antidiabetic, and anticancer properties (in terms of arresting the cell cycle and inducing apoptosis in HT29 colon cancer cells) were evaluated using cumin which was generated from Ayurvedic industry and the same was compared with that of the raw cumin. The results suggested that prevention or management of degenerative diseases is possible with the help of its concentrated extracts.
Research done on the effect of cuminaldehyde (CuA) on Human Lung Squamous Cells NCI-H520 Cells indicated inhibitory effects on growth of these cells. The same was inferred based on the observations viz., the upregulation of pro-apoptotic genes such as bax and bak and also downregulation of anti-apoptotic gene namely, bcl-2 and bcl-XL along with other physiological changes such as loss of mitochondrial membrane potential, cytochrome c release, activation of caspase 3 and 9, and morphological characteristics of apoptosis, including blebbing of the plasma membrane, nuclear condensation, fragmentation, apoptotic body formation, and comet with elevated tail intensity and moment. The above changes would always lead to suppressed proliferation and induced apoptosis. Adding on, CuA in dose dependent manner induce lysosomal vacuolation with increased VAC (volume of acidic compartments). Other cell lines such as human lung adenocarcinoma A549 cells and colorectal adenocarcinoma COLO 205 have also shown similar effects.
Significant augmentation of Cytochrome P450 and cytochrome b5 by dietary cumin were also observed. The phase II enzyme Glutathione-S-transferase (GST) was observed to have increased by cumin, whereas the specific activities of superoxide dismutase (SOD) and catalase were observed to have significantly elevated. Lipid peroxidation was inhibited by cumin, this suggested that the cancer chemo-preventive potential of cumin could be attributed to its ability to modulate carcinogen metabolism.
Most of the advantages because of consumption of cumin are indirectly related to apoptosis. Apoptosis is a series of programmed events that occur in a cell so as to remove unwanted cells. It is a 5 step process which includes shrinkage and fragmentation of cells and collapse of the cytoskeleton, dissemblance of nuclear envelope and the release of apoptotic bodies. As we all know cancer is uncontrolled cell growth which means that the cells abnormally start dividing without any checks. Apoptosis plays a major role in cancer cell growth prevention. Occurrence of apoptosis will terminate the growth of cancer cells and inducing the same sits very well with the plan of treating cancer.
Effect of cumin on high estrogen induced (E2) Breast Cancer:
The female ovary intact ACI rat model was used to study the effect of cumin on mammalian breast cancer. This model provides a physiologically relevant and genetically defined diet-hormone interactions in mammary cancer development. This model is considered to be highly relevant for understanding how the progression of human breast cancer (especially luminal breast cancer subtypes) occur along with its etiology. studies due to the fact that the estrogen-induced tumors. The high estrogen (E2) induced level circulation correlates with the levels that increase the risk of breast cancer in both premenopausal and postmenopausal women. Components present in cumin depicted significant delay and prevents E2 mediated mammary tumorigenesis in a safe and effective manner. This study correlated the effect of cumin seed powder and dried ethanolic cumin extract powder supplemented in diets against a control diet. A five-fold reduction in tumor volume along with significant reduction in tumor burden and tumor multiplicity was observed when both these diets were administered. The tumor reduction indices were achieved without affecting the body weight gain or causing any systemic toxicity. Tumor latency or delayed appearance of 1st tumor was also observed for both the diets. Growth of mammary glands require estrogen receptor alpha (Erα) which primarily is affected by E2. Cumin powder intervention reduced the Erα and cyclin D1 which suggested the anti-estrogenic nature of cumin phytochemicals. It has been documented that more than 50% of human breast cancers have overexpression of abnormal expression of cyclin D1. Intervention of cumin has significantly reversed the E2 mediated changes in genes such as CYP1A1 and CYP1B1. There was no systemic toxicity observed due to intake of cumin. Since the makeup of the hormones in both humans and mice are likely to be similar, the same advantage could be expected even in case of humans.
Cymene, one of the components present in cumin was found to be very effective in promoting in-vitro cytotoxic effects on HER2+ and RH+/HER2– breast cancer cells and also against BT474 breast cancer cells. Other components present in cumin namely carvacrol, germacrene D etc have also presented with strong anti-proliferative activity again breast cancer cells.
Studies have suggestive evidence that 1% of cumin extracts via diet have the capacity to inhibit cancer without having any chronic toxicity. This further appeals to the use of cumin to potentially develop as a chemo-preventive as well as an anti-cancer agent.
Mitochondrial protein (SMACs) involvement in cancerous cell growth:
SMACs (second mitochondria-derived activator of caspases), a mitochondrial protein, enters the cytosol of the cell which increases the permeability of the mitochondrial membrane. The cells have structurally and functionally similar set of proteins termed as IAPs (Inhibitor of apoptosis proteins) whose role is to allow the caspases (group of cysteine proteinases) to carry out apoptosis (programmed cell death). When SMACs gain entry into the cell it binds with IAPs hence repelling the inhibitory action on caspases which leads to lack of apoptosis. Hence unlimited growth occurs resulting in cancerous cells.
To tackle this inhibition, many assays with respect to different concentrations of CuA has been performed which in-turn has produced some promising results.
Fluorescence is a process wherein a substance or a material absorbs light (electromagnetic radiation) of a particular wavelength, and emits certain wavelength of light (due to excitation of atoms in them) usually in the visible range. Fluorescence is detected using a detector which has a film that catches these excited electrons and makes it visible.
Many experiments have been conducted based on the same principle to detect several aspects of cancerous growth in the presence of CuA such as caspase activity, mitochondrial membrane growth potential, and cell proliferation inhibitory activity to decrease cancerous cell growth. These are explained with more details below.
Assay on changes in caspase activity:
An assay was done to detect the caspases activity in which a fluorogenic chromophore namely AFC (7-amino-4-trifluoromethylcoumarin) was used. After treatment of the NCI-H520 Cells with different concentrations of CuA, changes were observed in the activities of key caspases (caspases 3 and caspases 9) which are involved in apoptotic reactions and this change was detected using fluorescence where free chromophore AFC emitted yellow green fluorescence at a particular wavelength. The results when compared to the untreated control was represented as a percentage change in the caspase activity.
Assay on mitochondrial membrane potential: A study conducted to check for mitochondrial membrane potential took up an assay where NCI-H520 Cells when treated with CuA under specific conditions, harvested and later stained using a mitochondrial specific fluorescent probe (JC-1) determined the change in mitochondrial membrane potential by change in the ratio of red and green fluorescence. The assay suggested that dose dependent administration of CuA opened up mitochondrial permeability transition pore which induced depolarization of transmembrane potential, further resulting in the release of apoptogenic factors leading to programmed cell death.
Cell proliferation inhibitory activity: Experiment conducted to analyze the cell proliferation inhibitory activity used NCI-H520 Cells and administered the with CuA (both dose and time dependent) along with AO (Acridine Orange staining) which resulted in blebbing, nuclear condensation and DNA fragmentation, further leading to inhibition of cell proliferation. It was followed by an Electrophoresis (Single cell gel electrophoresis) assay to determine the DNA strand breakage with different concentrations of CuA. As characteristics of apoptosis such as blebbing, nuclear condensation and fragmentation were included due to the presence of CuA, it was interpreted that CuA did play a major role in induction of apoptosis.
Other inhibitions due to CuA treatment:
Unusual inhibition of both the topoisomerases (I and II) could be the mechanism which drive the cells towards apoptosis.
Higher concentration of VAC (Volume of acidic compartment) is usually either due to apoptosis or necrosis. As CuA has been reported to induce elevated VAC, it can be helpful in curbing the growth of cancerous cells.
CuA and Apoptosis: Studies have suggested that there is more than one explanation for apoptosis upon treatment with CuA and these include:
Upregulated expression of Bax and Bak along with the downregulated expression of Bcl-2 and Bcl-XL.
Collapse of transmembrane potential of mitochondria.
Upregulated activities of most upstream proteases of intrinsic pathway, caspase-9 and the effector caspase-3.
Home cooked food (regular meals) using cumin would definitely add on to the health benefits.
Soak cumin seeds in water over night and drink it early in the morning (works better when taken in empty stomach).
Boiling water with cumin and having the same throughout the day also works.