Published Research

Unveiling the Groundbreaking Potential of Amorphical’s Nanoparticulate Amorphous Calcium Carbonate (ACC) in Cancer Therapy: Insights from Preclinical Studies and Clinical results

Amorphical has successfully managed to synthesize and produce nanoparticulate
amorphous calcium carbonate (ACC) having long-term stability. Amorphical’s ACC is the only
non-crystalline calcium carbonate supplement in the world.

The stabilized ACC technology is
based on biomimicry of the gastrolith in which the blue crayfish stores stabilized ACC. The
stabilized ACC allows the crayfish to regenerate its exoskeleton (one-third of its body mass)
within merely 3 days – a process that takes for other crustaceans about one month.
Amorphical has demonstrated that ACC’s solubility, fractional absorption, bioavailability, and
bioactivity are far superior compared to other calcium products, including products from the
world’s leading companies.

Cancer is the general name for a group of diseases involving uncontrolled growth of cells,
which mutate to form a malignant tumor capable of invading or spreading to other parts of
the body. A cancerous tumor creates a new system of blood supply in the tumor area and
has an ability for accelerated growth while evading attacks by the body’s immune system.
Amorphical’s scientists have been researching ACC’s usage as a potential anti-inflammatory
and anticancer therapy. Following a series of experimental observations, they began to
study ACC’s ability to successfully treat cancer due to its ability to modulate pH levels in
acidic environments. These environments allow cancer cells to flourish and spread. In
multiple preclinical studies conducted by Amorphical, ACC activity was repeatedly found to
be directly associated with anticancer activity by neutralizing the acidity.
Below is a summary of the preclinical studies performed by Amorphical and the influence of
ACC on cancer:

1. Cancer Cell Metabolism: One of the hallmark characteristics of cancer is shifting of
the cellular metabolic pathway (processing glucose into energy) from oxidative
phosphorylation to “aerobic” glycolysis. This shift simultaneously generates lactate
and hydrogen ions (protons), even when there are sufficient oxygen levels, thus
making the environment more acidic. A study performed with murine breast cancer
cells showed that culturing in the presence of ACC suppressed the lactate metabolic
route and increased the rate of the favorable oxidative phosphorylation pathway.
This change did not occur in the presence of other calcium sources [crystalline
calcium carbonate (CCC) or dissolved calcium chloride (CaCl2)].

2. Differential gene expressions indicating strengthening the immune system and
inhibiting cancer activity: The addition of ACC to various human cancer cell cultures
was found to up- or downregulate multiple gene expressions in a way promoting an
anticarcinogenic phenotype. This phenotype is associated with reduced proliferation
rates and an enhanced immune-system ability to fight cancer cells. Various
influences of this sort were found for the following human cell lines: acute myeloid
leukemia, prostate, lung, breast (two lines: (1) triple negative and (2) hormone
positive cells), colorectal cancer, and cervical cancer cells.

3. Increased survival and reduction of tumor growth rate: In preclinical studies of bone
metastases model of breast cancer cells animals treated with ACC had higher survival rates
compared to control group animals.
Other studies done with a subcutaneous model of lung cancer in mice (Lewis Lung
Carcinoma) revealed that tumors’ growth rates decreased significantly compared to the
control group. In a xenograft study in which human lung cancer cells were injected into nude
mice (mice with a compromised immune system), tumors’ growth rates of the ACC-treated
mice were significantly lower relative to the control animals.

4. Reduction of the enzymatic activity of Cathepsin B:
Cathepsin B is a cysteine protease, an enzyme that breaks down proteins. Its high levels are
found in malignant tumors. Cathepsin B is active only under acidic environments, and high


levels of Cathepsin B are associated with tumor advancement, metastases creation, and
development of associated inflammations.
Cathepsin B activity was assessed in mice with subcutaneous Lewis lung carcinoma (in
tandem with the reduced tumor’s growth rates) that were treated with ACC, in comparison
to control mice. The results exhibited a significant reduction of Cathepsin B activity for the
ACC-treated mice groups, compared to the control group.
Amorphical Strives to Revolutionize Cancer Treatment
Our preclinical studies have demonstrated ACC’s ability to inhibit tumor growth, most likely
via its ability to modulate the relatively low pH in tumor’s microenvironment.
In summary, the combined studies suggest that ACC:

1. Modulates acidity in inflammatory environment;
2. Improves/enhances immune response against the tumors and malignant cells;
3. Reduces the activity of Cathepsins (especially Cathepsin B, which helps tumors’
4. May slow down and alter the evolution of new blood vessels, hence decreasing nutrition
to the tumor cells;
5. Changes cancer cells’ metabolism towards oxidative phosphorylation; and
6. Affects the cancer cells’ genetic expressions in modes that suppress the malignant
activities and the resistance to the immune system of the body.

Amorphical’s initial clinical trials in patients with various types of terminal cancer, who had
exhausted other regulated treatment options, have also indicated that ACC has anticancer
potential, is a safe treatment even in relatively high doses, and does not exhibit the severe
and traumatic side effects of standard cancer therapies.
Encouraged by these accumulated results, Amorphical is planning to conduct additional
controlled clinical studies with larger groups of advanced cancer patients, for a more
extensive examination of ACC’s potential in specific types of cancer. Successful studies will
lead to novel treatments that revolutionizing the world of healthcare.
Amorphical published an article explaining the mechanism and showing the results of work
in using ACC to treat various types of cancer.

“Amorphous Calcium Carbonate Shows Anti-Cancer Properties That Are Attributed
to Its Buffering Capacity”
Yehudit Natan ,*, Yigal Dov Blum , Amir Arav , Ylena Poliansky , Sara Neuman , Orit Ecker Cohen and
Yossi Ben

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