Chandran K C Explains Homeopathy As Molecular Imprints Therapeutics (MIT)

‘Molecular Imprints’ Of ‘Beta Catenin’- A Highly Promising ‘Homeopathic’ Weapon In The Fight Against Cancers

Scientists and cancer researchers have lately identified a particular biological molecule in our body known as BETA CATENIN as an ideal molecular target for anti-cancer therapy. They have been trying to develop drugs that could inhibit the over-expressions and aberrations of BETA CATENIN, which is recognized to be playing a big role in the biochemical processes underlying various types of cancers. Their attempts have not been so far successful, since any chemical compound they develop to target BETA CATENIN will inevitably have serious harmful effects upon the organism, since it is an essential biological molecule having diverse roles normal vital processes, and its complete inhibition may lead to be very dangerous consequences.

BETA CATENIN is a protein found as part of molecular complexes in forming cadherin cell adhesion factors of animal cells. It belongs to a family of biological compounds known as catenins, consisting of alpha catenin, beta catenin and gamma catenin. B-CATENIN binds the cytoplasmic domain of some cadherins. Cell-cell adhesion complexes are required for simple epithelia in higher organisms to maintain structure, function and polarity. These complexes, which help regulate cell growth in addition to creating and maintaining epithelial layers, are known as ‘adherens junctions’ and they typically include at least cadherin, beta catenin, and alpha catenin. Catenins play roles in cellular organization and polarity long before the development and incorporation of ‘Wnt signaling pathways’ and cadherins.

BETA CATENIN is a dual function protein, regulating the coordination of cell–cell adhesion and gene transcription. In humans, this protein is encoded by the CTNNB1 gene. β-catenin is a subunit of the cadherin protein complex and acts as an intracellular signal transducer in the Wnt signaling pathway.


The primary mechanical role of catenins is connecting cadherins to actin filaments, specifically in these adhesion junctions of epithelial cells. Most studies investigating catenin actions focus on alpha catenin and beta catenin. Beta catenin is particularly interesting as it plays a dual role in the cell. First of all, by binding to the intracellular cytoplasmic tail domains of cadherin receptors, it can act as an integral component of a protein complex in adherens junctions that helps cells maintain epithelial layers. Beta catenin acts basically by anchoring the actin cytoskeleton to the adherens junctions, and also aid in contact inhibition signaling within the cell. For instance, when an epithelial layer is complete and the adherens junctions indicate that the cell is completely surrounded, beta catenin may play a role in telling the cell to stop proliferating, as there is no room for more cells in the area. Secondly, beta catenin participates in the ‘Wnt signaling pathway’ as a downstream target.

The Wnt signaling pathways are a group of signal transduction pathways made of proteins that pass signals from outside of a cell through cell surface receptors to the inside of the cell. Wnt/ beta catenin pathway, also known as canonical Wnt pathway is the Wnt pathway that causes an accumulation of beta catenin in the cytoplasm and its eventual translocation into the nucleus to act as a transcriptional coactivator of transcription factors that belong to the TCF/LEF family. Without Wnt signaling, the beta catenin would not accumulate in the cytoplasm since a destruction complex would normally degrade it. This destruction complex includes the following proteins: Axin, adenomatosis polyposis coli (APC), protein phosphatase 2A (PP2A), glycogen synthase kinase 3 (GSK3) and casein kinase 1a (CK1α). It degrades beta catenin by targeting it for ubiquitination, which subsequently sends it to the proteasome to be digested. However, as soon as Wnt binds Fz and LRP-5/6, the destruction complex function becomes disrupted. This is due to Wnt causing the translocation of both a negative regulator of Axin and the destruction complex to the plasma membrane. This negative regulator becomes localized to the cytoplasmic tail of LRP-5/6. Phosphorylation by other proteins in the destruction complex subsequently binds Axin to this tail as well. Axin becomes de-phosphorylated and its stability and levels are decreased. Dsh then becomes activated via phosphorylation and its DIX and PDZ domains inhibit the GSK3 activity of the destruction complex. This allows beta catenin to accumulate and localize to the nucleus and subsequently induce a cellular response via gene transduction alongside the TCF/LEF .

In general, when ‘Wnt’ is not present, GSK-3B (a member of the pathway) is able to phosphorylate beta catenin as a result of a complex formation that includes beta catenin, AXIN1, AXIN2, APC (a tumor suppressor gene product), CSNK1A1, and GSK3B. Following phosphorylation of the N-terminal Serine and Thrionin residues of beta catenin, BTRC promotes its ubiquitination, which causes it to be degraded by the TrCP/SKP complex. On the other hand, when ‘Wnt’ is present, GSK-3B is displaced from the previously mentioned complex, causing beta catenin to not be phosphorylated, and thus not ubiquitinated. As a result, its levels in the cell are stabilized as it builds up in the cytoplasm. Eventually, some of this accumulated beta catenin will move into the nucleus. At this point, beta catenin becomes a co-activator for TCF and LEF to activate ‘Wnt genes’ by displacing Groucho and HDAC transcription repressors. These ‘Wnt’ gene products are important in determining cell fates during normal development and in maintaining homeostasis, or they can lead to de-regulated growth in disorders like cancer by responding to mutations in beta catenin, APC or Axin, each of which can lead to this de-regulated beta catenin level stabilization in cells.

Beta-catenin has a central role in directing several developmental processes, as it can directly bind transcription factors and be regulated by a diffusible extracellular substance- Wnt. It acts upon early embryos to induce entire body regions, as well as individual cells in later stages of development. It also regulates physiological regeneration processes.

Wnt signaling and beta-catenin dependent gene expression plays a critical role during the formation of different body regions in the early embryo. Experimentally modified embryos that do not express this protein will fail to develop mesoderm and initiate gastrulation. It also plays a role in inducing the antero-posterior axis formation, regulate the precise placement of the primitive streak (gastrulation and mesoderm formation) as well as the process of neurulation (central nervous system development).

Beta catenin is initially equally localized to all regions of the egg, but it is targeted for ubiquitination and degradation by the beta catenin destruction complex. Fertilization of the egg causes a rotation of the outer cortical layers, moving clusters of the Frizzled and Dsh proteins closer to the equatorial region. Beta catenin will be enriched locally under the influence of ‘Wnt’ signaling pathway in the cells that inherit this portion of the cytoplasm. It will eventually translocate to the nucleus in order to activate several genes that induce dorsal cell characteristics. This signaling results in a region of cells known as the grey crescent, which is a classical organizer of embryonic development. If this region is surgically removed from the embryo, gastrulation does not occur at all. Beta Catenin also plays a crucial role in the induction of the blasopore lip, which in turn initiates gastrulation. Inhibition of GSK-3 translation by injection of antisense mRNA may cause a second blastopore and a superfluous body axis to form. A similar effect can result from the over expression of beta catenin.

Beta-catenin has also been implicated in regulation of cell fates through asymmetric cell division in the model organisms. One of the most important results of Wnt signaling and the elevated level of beta-catenin in certain cell types is the maintenance of pluripotency. In other cell types and developmental stages, beta catenin may promote differentiation, especially towards mesodermal cell lineages.

Beta-catenin also acts as a morphogen in later stages of embryonic development. Together with TGF beta, an important role of beta catenin is to induce a morphogenic change in epithelial cells. It induces them to abandon their tight adhesion and assume a more mobile and loosely associated mesenchymal phenotype. During this process, epithelial cells lose expression of proteins like E- cadherin, Zonula occludens 1and cytokeratin. At the same time they turn on the expression of vimentin, alpha smooth muscle actin(ACTA2), and fibroblast-specific protein 1 (FSP1). They also produce extracellular matrix components, such as type 1 collagen and fibronectin.. Aberrant activation of the Wnt pathway has been implicated in pathological processes such as fibrosis and cancer.


The same properties of beta catenin that give it an important role in normal cell fate determination, homeostasis and growth of cells, also make it susceptible to alterations that can lead to abnormal cell behavior and growth that leads to cancerous changes in the cells.

Any changes in cytoskeletal organization and adhesion can lead to altered signaling, migration and a loss of contact inhibition that can promote cancer development and tumor formation. In particular, beta catenin have been identified to be major player in aberrant epithelial cell layer growth associated with various types of cancer. Mutations in genes encoding these proteins can lead to inactivation of cadherin cell adhesions and elimination of contact inhibition, allowing cells to proliferate and migrate, thus promoting tumorigenesis and cancer development. Beta catenin is known to be associated with colorectal and ovarian cancer, and they have been identified in cancers such as pilomatrixoma, medulloblastoma, pleomorphic adenomas, and malignant mesothelioma. Mutations and overexpression of β-catenin are associated with many cancers, including hepatocellular carcinoma, colorectal carcinoma, lung cancer, malignant breast tumors, ovarian and endometrial cancer. Major B-CATENIN associated cancers are: colorectal and ovarian cancer; pilomatrixoma; medulloblastoma; pleomorphic adenomas; malignant mesothelioma. β-catenin is regulated and destroyed by the beta-catenin destruction complex, and in particular by the adenomatous polyposis coli (APC) protein, encoded by the tumour-suppressing APC gene. Therefore genetic mutation of the APC gene is also strongly linked to cancers, and in particular colorectal cancer resulting from familial adenomatous polyposis (FAP).

While less is known about the exact mechanism of alpha catenin, its presence in cancer is also widely felt. Through the interaction of beta catenin and alpha catenin, actin and E-cadherin are linked, providing the cell with a means of stable cell adhesion. However, decrease in this adhesion ability of the cell has been linked to metastasis and tumor progression. In normal cells, alpha catenin may act as a tumor suppressor and can help prevent the adhesion defects associated with cancer. On the other hand, a lack of alpha catenin can promote aberrant transcription, which can lead to cancer. As a result, it can be concluded, that cancers are most often associated with decreased levels of alpha catenin.
BETA CATENIN plays a more significant role in various forms of cancer development. However, in contrast to alpha catenin, heightened beta catenin levels may be associated with carcinogenesis. In particular, abnormal interactions between epithelial cells and the extracellular matrix are associated with the over-expression of these beta catenin and their relationship with cadherins in some cancers. Stimulation of the Wnt/β-catenin pathway, and its role in promoting malignant tumor formations and metastases, has also been implicated in cancers.

Mutations in catenin genes can cause loss of contact inhibition that can promote cancer development and tumor formation.

Beta-catenin is a proto oncogene. Mutations of this gene are commonly found in a variety of cancers- in primary hepatocellular carcinoma, colorectal cancer, ovarial carcinoma, breast cancer, lung cancer and glioblastoma. It has been estimated that approximately 10% of all tissue samples sequenced from all cancers display mutations in the CTNNB1 gene. Most of these mutations cluster on a tiny area of beta catenin. Loss-of-function mutations of beta catenin essentially make ubiquitinylation and degradation of beta catenin impossible. It will cause beta catenin to translocate to the nucleus without any external stimulus and continuously drive transcription of its target genes. Increased nuclear β-catenin levels have also been noted in basal cell carcinoma (BCC), head and neck squamous cell carcinoma (HNSCC), prostate cancer (CaP), pilomatrixoma (PTR) and medulloblastoma (MDB). These observations may or may not implicate a mutation in the beta catenin gene: other Wnt pathway components can also be faulty.

Similar mutations are also frequently seen in the beta catenin recruiting sites of APC. Hereditary loss-of-function mutations of APCcause a condition known as Familial Adenomatous Polyposis. Affected individuals develop hundreds of polyps in their large intestine. Most of these polyps are benign in nature, but they have the potential to transform into deadly cancer as time progresses. Somatic mutations of APC in colorectal cancer are also not uncommon. Beta-catenin and APC are among the key genes involved in colorectal cancer development. The potential of beta catenin to change the previously epithelial phenotype of affected cells into an invasive, mesenchyme-like type contributes greatly to metastasis formation.

Mutations associated with aberrant epithelial cell layer growth due to lack of adhesions and contact inhibition Down-regulated levels of α-catenin Up-regulated levels of β-catenin Stimulation of the Wnt/β-catenin pathway Catenin alteration (and Wnt/β-catenin pathway up-regulation) may help stimulate epithelial-mesenchymal transition (or EMT) Mutations or aberrant regulation of catenins may also associate with other factors that promote metastasis and tumorigenesis Treatments focus on correcting aberrant catenin levels or regulating catenin pathways that are associated with cancer development and progression.

The role of catenin in epithelial-mesenchymal transition (or EMT) has also received a lot of recent attention for its contributions to cancer development. It has been shown that HIF-1α can induce the EMT pathway, as well as the Wnt/β-catenin signaling pathway, thus enhancing the invasive potential of LNCaP cells (human prostate cancer cells). As a result, it is possible that the EMT associated with upregulated HIF-1α is controlled by signals from this Wnt/β-catenin pathway. Catenin and EMT interactions may also play a role in hepatocellular carcinoma. VEGF-B treatment of hepatoma carcinoma cells can cause alpha catenin to move from its normal location on the membrane into the nucleus and E-cadherin expression to decrease, thus promoting EMT and tumor invasiveness.

There are other physiological factors that are associated with cancer development through their interactions with catenins. For instance, higher levels of collagen XXIII have been associated with higher levels of catenins in cells. These heightened levels of collagen helped facilitate adhesions and anchorage-independent cell growth and provided evidence of collagen XXIII’s role in mediating metastasis. In another example, Wnt/β-catenin signaling has been identified as activating microRNA-181s in hepatocellular carcinoma that play a role in its tumorigenesis.


Recently, there have been a number of studies in the lab and in the clinic investigating new possible therapies for cancers associated with beta catenin. Integrin antagonists and immonochemotherapy with drugs such as 5-fluorouracil and polysaccharide-K have shown promising results. Polysaccharide K can promote apoptosis by inhibiting NF-κB activation, which is normally up-regulated, and inhibiting apoptosis, when beta catenin levels are increased in cancer. Therefore, using polysaccharide K to inhibit NF-κB activation can be used to treat patients with high beta catenin levels, which is recognized to be a major contributing factor in cancer formation.

In the short-term, combining current treatment techniques with new drugs targeting catenin-associated elements of cancer is expected by researchers to be a most effective way of treating the cancer. By disrupting Wnt/β-catenin signaling pathways, short-term neoadjuvant radiotherapy (STNR) may help prevent clinical recurrence of the disease after surgery, but much more work is needed before an adequate treatment based on this concept can be determined.

Research studies have also implicated potential therapeutic targets for future clinical studies. VEGFR-1 and EMT mediators may be ideal targets for preventing cancer development and metastasis. 5-aminosalicylate (ASA) has been shown to reduce β-catenin and its localization to the nucleus in colon cancer cells isolated from and in patients. As a result, it may be useful as a chemopreventative agent for colorectal cancer. Additionally, acyl hydrazones have been shown to inhibit the Wnt signaling characteristic of many cancers by destabilizing β-catenin, thus disrupting Wnt signaling and preventing the aberrant cell growth associated with cancer. On the other hand, some treatment concepts involve upregulating the E-cadherin/catenin adhesion system to prevent disruptions in adhesions and contact inhibition from promoting cancer metastasis. One possible way to achieve this, which has been successful in mouse models, is to use inhibitors of Ras activation in order to enhance the functionality of these adhesion systems. Other catenin, cadherin or cell cycle regulators may also be useful in treating a variety of cancers.

While recent studies in the lab and in the clinic have provided promising results for treating various catenin-associated cancers, the Wnt/β-catenin pathway may make finding a single correct therapeutic target difficult as the pathway has been shown to elicit a variety of different actions and functions, some of which may possibly even prove to be anti-oncogenic.

Due to its involvement in cancer development, inhibition of beta-catenin continues to receive significant attention. But the targeting of the binding site on its armadillo domain is not the simplest task, due to its extensive and relatively flat surface. However, for an efficient inhibition, binding to smaller “hotspots” of this surface is sufficient. This way, a “stapled” helical peptide derived from the natural beta catenin binding groups found in LEF1 was sufficient for the complete inhibition of beta catenin dependent transcription. Recently, several small-molecule compounds have also been developed to target the same. In addition, beta catenin levels can also be influenced by targeting upstream components of the Wnt pathway as well as the beta catenin destruction complex. The additional N-terminal binding pocket is also important for Wnt target gene activation. This site can be pharmacologically targeted by carnosic acid, for example. That “auxiliary” site is another attractive target for drug development. Despite intensive preclinical research, no beta catenin inhibitors are available as therapeutic agents yet.


In my opinion, Molecular Imprints of BETA CATENIN could be effectively used as a therapeutic agent to inhibit the over expression and aberrant actions of this biological component that plays a crucial role in development of cancers. Since molecular imprints cannot interfere in the NORMAL interactions between biological molecules and their natural ligands, their use will not any way disrupt the normal biochemical processes involving BETA CATENIN.

BETA CATENIN potentized above 12C or Avogadro limit will contain only molecular imprints, and as such, will be a very effective and safe therapeutic weapon in our fight against various types of cancers such as hepatocellular carcinoma, lung cancer, malignant breast tumors, endometrial cancer, colorectal cancer, ovarian cancer, pilomatrixoma, medulloblastoma, pleomorphic adenomas, malignant mesothelioma, basal cell carcinoma, head and neck squamous cell carcinoma, prostate cancer, pilomatrixoma and various metastases. Since aberrations and over expression of BETA CATENIN is implicated in more and more types of cancers, use of MOLECULAR IMPRINTS of beta catenin could be proved in future as a general therapeutic approach to cancer.

I would request scientists and cancer researchers to explore more in this direction. It will herald a new revolution in cancer treatment.

Apart from molecular imprints of beta catenin, from homeopathic point of view, any drug substance that can induce over expression of BETA CATENIN in healthy individuals can act as anti-cancer drugs if used in potentized or molecular imprints forms. This realization leads us to the possibility of exploring various existing homeopathic drugs that have shown anti-cancer properties, from a biochemical angle. Such drugs have to be scientifically re-proved to verify whether they can induce over expression of beta catenin during drug proving.

(This is not an original work of the author. This study is based on information collected and extracted from various biochemistry texts as well as Wikipedia articles. But the concepts of ‘molecular imprints of beta catenin for cancer therapy’ is the original idea of the author )

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