Cancer
Cancer is a deadly disorder resulting in the uncontrolled proliferation of cells in different parts of the body.
This deadly disease results from some genetic factors and also from exposure to some environmental mutagens.
Although great research is being carried out in all parts of the world to find out some specific cure for cancer, no significant outcome has been found yet. Therefore, the need of the hour is to go for new and effective treatments for the disease [1].
Curcumin and Cancer
Curcumin is a natural compound that is found in the spice turmeric, and it possesses many important biological activities that have positive outcomes in cancer prevention and treatment.
In particular, it is found that curcumin can induce apoptosis, stop the proliferation of malignant cells, and suppress angiogenesis in malignant cells.
Additionally, this crucial compound is found to enhance the efficacy of conventional cancer treatments, such as chemotherapy and radiation therapy.
It has been found that curcumin also has a role in the medication of certain malignancies by inhibiting the cancer cells’ growth or by enhancing the effectiveness of traditional therapies such as chemotherapy.
Curcumin may also help prevent cancer by causing cell death in abnormal cells and reducing inflammation, which some researchers believe can contribute to cancer [2].
How Curcumin Works at Molecular Level in Cancer Cells
At the genetic level in cancer, curcumin exerts its anticancer influences by targeting different signaling pathways in the malignant cells that are important in the development of different cancer types.
One of the key processes by which this compound kills cancer cells is by inducing programmed cell death in these malignant cells.
Apoptosis is a natural phenomenon essential for maintaining homeostasis in the body of a living organism, and if this process is dysregulated, it can lead to multiple types of cancer.
Curcumin can kill malignant cells by different mechanisms of action, including upregulation of caspases proteins, downregulation of anti-apoptotic proteins, and induction of oxidative stress.
Genes Influenced by Curcumin in Malignant Cells
Curcumin can target different genes in the cancer cells that are part of different signaling transduction pathways essential for the progression and survival of these malignant cells. Following genes have been reported that can be a target for curcumin in cancer cells [4].
1. MAPK
2. NFκB
3. PI3K/AKT
4. STAT3
5. TP53
6. BCL-2
7. EGFR
8. Ras
9. JNK
10. c-Myc
11. CDKs
12. MMPs
MAPK
The influence of curcumin compound on MAPK pathways in cancer is influenced by the type of cancer and the specific MAPK involved.
In general, curcumin has been found to inhibit MAPK pathways in tumor cells. It is found that this compound can reduce the phosphorylation of Ras, MEK, and ERK, which are key factors in MAPK signaling pathways.
Additionally, curcumin also reduces the activation of many important transcription factors in the cell which act downstream of MAPK signaling pathways [5].
NFkB
NFkB is a protein in the cell that has a role in the control of cell survival, inflammation, division, and other processes in cancer cells.
Curcumin is found to directly target NFKb in cancer cells by acting as an inhibitor of this protein.
It works by inducing the nuclear export of NF-kB, thus preventing its activation and blocking the expression of multiple genes that play roles in cancer progression and development.
Curcumin is proven experimentally to be very useful against cancer as it can inhibit NFKB activation in cancer cells.
NFkB is a specific factor that is implicated in the inflammatory pathways and the promotion of cancer cell growth and survival. By inhibiting NFkB activation, curcumin can decrease inflammation, which can decrease the risk of getting cancer disorder.
Additionally, NFkB is related to the progression of many other diseases, such as pancreatic disorders [6].
PI3K/AKT
Experimental findings have also shown that curcumin can inhibit PI3K/AKT pathway in cancer.
This pathway has an important role in the proliferation of malignant cells, their survival, and the metastasis of malignant cells.
Experimental research has demonstrated that curcumin can reduce the activity of PI3K/AKT in different types of cancers.
It appears to do this by blocking the phosphorylation of Akt, a key component of this pathway, thus inhibiting the pathway indirectly and stopping the proliferation of tumor cells [7].
STAT3
It is found that curcumin acts on different biological pathways associated with cancer, including reducing cellular levels of the transcription factor STAT3.
In various cancers, curcumin has been found to directly inhibit STAT3, resulting in reduced tumor size and growth.
Additionally, curcumin interacts with the Akt and NF-κB pathways, which then results in reduced expression of STAT3 and subsequent anti-cancer behavior.
Thus, by downregulating the expression of STAT3 in the malignant cells, curcumin can inhibit cancer cell growth [8].
TP53
It is also found that curcumin can upregulate the TP53 pathways in malignant cells.
It can not only induce the expression of TP53 in cancer cells but as well as upregulate its transcriptional activity, resulting in increased levels of p53-dependent gene expression and increased levels of apoptosis.
Thus, by stimulating the expression of TP53, Curcumin can induce programmed cell death in the malignant cells resulting in reduced tumor size [9].
BCL2
Curcumin has been found to significantly reduce BCL2 protein expression in cancer cells.
Additionally, curcumin can induce cell death in malignant cells by upregulating caspase-dependent pathways and promoting mitochondrial damage, which further suggests its ability to reduce the protective effect of BCL2.
Thus, curcumin has the possibility to prevent BCL2 expression and activity in malignant cells, leading to the killing of these malignant cells [10].
EGFR
EGFR is a receptor found on the surface of cells, that is commonly over-expressed in many types of malignancies and is thought to be a key player in the progression of tumor growth.
A polyphenol, curcumin, has a role in stopping the growth of cancer cells and has been studied for its potential to inhibit EGFR signaling in tumor cells.
Studies have demonstrated that curcumin has the capability to suppress EGFR and inhibit the growth of malignant cells in different types of cancers resulting in reduced tumor size [11].
Ras
Ras is a signaling protein found in all cells playing a role in the division of cells. In malignant cells, this protein is overexpressed, leading to increased proliferation of these cells.
Curcumin can inhibit Ras-mediated signaling pathways, like the NF-κB and MAPK/ERK, which are involved in the development of tumors.
This compound can inhibit the expression of Ras-related GTPases, which are involved in the regulation of Ras. Thus, resulting in the inhibition of tumor growth [12].
JNKs
It is found through experiments that curcumin can influence the JNK pathway and inhibit its activity in tumor cells.
JNK is a kinase (JNKs) and is a crucial player in the division of cells, their differentiation, as well as death.
In cancer cells, the JNK pathway is hyper-activated, resulting in aberrant cell growth and survival.
This important anti-cancerous compound can inhibit JNK activity in the malignant cells leading to decreased cellular survival in case of malignancy [13].
c-myc
Curcumin also has a significant effect on c-myc expression in cancer cells as shown by experimental findings.
It has been observed to downregulate c-myc expression, which is related to the inhibition of cell growth and proliferation.
Curcumin is thought to inhibit the progression of the cell cycle as well as decrease the activity of c-myc by interfering with multiple pathways related to cell cycle regulation.
It has been suggested that curcumin is able to reduce the expression of c-myc in cancer cells and make their survival difficult [14].
MMPs
Curcumin is found to have multiple anti-cancer effects on cancer cells at the molecular level.
It can activate the body's own antioxidant defense system, inhibit the growth of new blood vessels that supply tumors, and modulate genes involved in cell division and apoptosis.
This compound also has the capability to downregulate the expression of various oncogenes, including COX-2, NF-kB, Bcl-2, and MMP-9.
In addition to inducing apoptosis and inhibiting cell proliferation, curcumin also targets angiogenesis.
Angiogenesis is very crucial for cancer growth as well as metastasis of tumor cells, as it provides the tumor with essential nutrients and oxygen.
Curcumin inhibits the process of angiogenesis by downregulating the activity of specific factors, such as VEGF. It can also do so by downregulating the activity of pro-angiogenic enzymes, for example, matrix metalloproteinases (MMPs) [15].
CDKs
Another mechanism by which curcumin inhibits cancer growth is by inhibiting cell proliferation.
Cancer cells have an uncontrolled cell cycle, which results in unregulated cell division and growth.
Curcumin helps to stop the cell cycle at G1, S, and G2/M phases, thereby preventing further cell division and proliferation.
The compound achieves this by targeting several regulatory proteins of the cell cycle, such as cyclins, CDKs, as well as CDK inhibitors [16].
Conclusion
In conclusion, curcumin has emerged as a promising natural compound with significant anticancer activity.
The compound exerts its effects at the molecular level, by targeting different signaling pathways in the cancer cells.
Its ability to induce apoptosis, inhibit cell proliferation, suppress angiogenesis, and enhance the efficacy of conventional cancer treatments makes it a promising candidate for cancer prevention and treatment.
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