Silver Nanoparticles Kill Colon Cancer Cells: 12 Studies

By Steve Barwick, author, The Ultimate

Colloidal Silver Manual
According to the CDC, “Of cancers that
affect both men and women, colorectal
cancer is the second leading cause of
cancer-related deaths in the United States.
It is the third most common cancer in men
and in women.”
Indeed, there are as many as 135,430 new cases of colon and rectal cancers in the
U.S. each year, resulting in 50,260 deaths. One in every 20 people will be diagnosed
with colorectal cancer (colon or rectal cancer).
New Studies Demonstrate Silver Kills Colon Cancer Cells
Thankfully, there have been a growing number of in vitro (i.e., “test tube”) clinical
studies over the last 10 years using various forms of antimicrobial silver against colon
cancer cells, each of which have demonstrated silver’s effectiveness against the cancer
cells. We’ll take a quick look at twelve of these studies, below.
For example, the according to a 2012 article in the UK Daily Mail, titled “Silver Bullet for
Cancer: Metal Can Kill Some Tumours Better than Chemotherapy with Fewer Side
Effects,” we find the following fascinating information:
“Researchers from the University of Leeds conducted lab tests which exposed breast and
colon cancer cells to various silver-based chemicals over a six day period.
Results, published in journal Dalton Transactions, showed that these silver-compounds
were ‘as effective as Cisplatin’ at killing cancer with potentially fewer side effects.
While the team are still unsure about how exactly silver battles cancer, they think its
effectiveness may be caused by the structure surrounding silver atoms, known as its
ligand.
They think this may help release the silver ion into cells when it enters the body, killing any
cancer.
Study author Dr Charlotte Willans plans to spend the next year looking closely at what
effect silver has on both cancerous and healthy cells, and whether it could be a safe and
effective new anti-cancer drug.”
So in the above-mentioned study, which was titled “Enhanced Cytotoxicity Of Silver
Complexes Bearing Bidentate N-Heterocyclic Carbene Ligands” the silver-based
chemicals proved to be as effective against breast cancer cells and colon cancer cells
as the popular anti-cancer chemotherapy drug, Cisplantin, but with fewer side effects.
According to Dr. Willans, who authored the study, “This could lead to a cheaper, less
toxic alternative to current treatments for cancer.”
A Second Interesting Clinical Study
According to a clinical study published in February 2011 and titled “Induction Of
Apoptosis In Cancer Cells At Low Silver Nanoparticle Concentrations Using Chitosan
Nanocarrier,” clinical researchers coated silver nanoparticles in a chitosan-based
carrier and then used them on a colon cancer cell line.
The result? “Using a considerably lower concentration of silver nanoparticles, they
efficiently induced apoptosis through ROS generation in human colon cancer cells (HT 29).”
In other words, the researchers created a novel silver compound made out of
chitosan (carbohydrate sugar molecules) and silver nanoparticles. (Keep in mind that
researchers create these “novel” silver compounds so they can afterwards patent the
process and potentially sell the end-product to Big Pharma as a “drug.”)
They then tested these silver nanoparticles on the HT 29 line of human colon cancer
cells. The result was that very small concentrations of the nanosilver were needed to
cause the colon cancer cells to die.
Upon contact with the colon cancer cells, the silver nanoparticles induced ROS (i.e.,
“reactive oxygen species,” which is similar in effect of hydrogen peroxide) causing the
unhealthy cancer cells to begin dying off.
Most exiting was the fact that a concentration of less than 1 ppm (actually, closer to 1
ppb — a nearly insignificant amount) of the silver nanoparticles was all it took to
reduce the colon cancer cell growth by 50% (in a test tube), which the study authors
say was “much less than in previously reported data.”
A Third Clinical Study
But those aren’t the only clinical studies demonstrating silver to be effective against
colon cancer cells.
Indeed, in a study titled “Anticancer Activity of Biosynthesized Silver Nanoparticles
using Murraya koenigii Leaf Extract against HT-29 Colon Cancer Cell Line,” silver
nanoparticles that were manufactured using curry leaf extract (another “novel”
method of creating patentable silver nanoparticles) and then exposed to an HT-29
colon cancer cell line.
The study, published in the Journal of Cancer Science & Therapy in 2018, concluded as
follows:
“The anticancer potential of the nanoparticles was evaluated using MTT assay on HT-29
colon cancer cell line.
Ag NPs showed potent cytotoxic activity against the human colorectal adenocarcinoma (HT-
29) cell line at higher concentrations [i.e., 82.39, 83.57 and 78.78 ppm].
This study insights the M. koenigii synthesized silver NP’s could be an effective applicability
drug candidate for colon cancer.”
In other words, silver nanoparticle concentrations ranging from 78 ppm to 83 ppm
demonstrated “potent cytotoxic activity” against the cancer cell line. And the
researchers characterized the silver nanoparticles as potential candidates for colon
cancer treatment.
A Fourth Clinical Study
In another study, published in the journal Nanomedicine in March 2013 and titled
“Silver-Based Nanoparticles Induce Apoptosis in Human Colon Cancer Cells Mediated
Through P53,” researchers wrote:
“The authors have systematically investigated the anticancer potentiality of silver-based
nanoparticles (AgNPs) and the mechanism underlying their biological activity in human
colon cancer cells.
…Starch-capped AgNPs were synthesized, characterized and their biological activity
evaluated through multiple biochemical assays. Results: AgNPs decreased the growth and
viability of HCT116 colon cancer cells. AgNP exposure increased apoptosis…
…In the present report, we have shown for the first time that AgNps exhibit anticancer
activity in colon cancer cells and determined the mechanism of action. This study has
systematically established the anticancer activity of AgNPs against colon cancer cells.
… Conclusion: The data provide strong evidence that AgNPs should be studied further as
potential novel anticancer agents to treat colon cancer with an interesting mechanism of
action.
…AgNPs are bona fide anticancer agents that act in a p53-dependent manner.”
Wow. Like the other studies, this one too found that silver nanoparticles, upon contact
with the colon cancer cells, caused them to commit cellular suicide (i.e., apoptosis).
You may have noticed in the quote above that the researchers used “starch-capped”
silver nanoparticles — once again, a way of creating a “novel” silver compound that
can later be patented and utilized as a “drug.”
A Fifth Clinical Study
In another study, this one titled “Exposure to Silver Nanoparticles Induces Size- and
Dose-dependent Oxidative Stress and Cytotoxicity in Human Colon Carcinoma Cells”
and published in July 2014 in the journal Toxicology In Vitro, clinical researchers once
again set out to evaluate the effects of silver nanoparticles against human colon
cancer cells.
The researchers tested “the size-dependent effects of AgNPs by treating the human LoVo
cell line, an intestinal epithelium model, with spherical AgNPs of well-defined sizes (10, 20,
40, 60 and 100nm).”
In other words, they decided to test silver particles of five different particle sizes
against colon cancer cells.
Results: The smaller the silver particles were, the more effectively they penetrated the
cancer cells, resulting in the “stimulation of a signaling cascade that generated ROS
and inflammatory markers, leading to mitochondrial dysfunction and subsequently
inducing apoptosis.”
In other words, the smallest silver particles caused the colon cancer cells to self-
destruct, whereas the largest of the silver particles (100 nm) could not even penetrate
the cancer cells. This once again proves the old maxim that when it comes to
silver, smaller silver particles truly work better.
A Sixth Clinical Study
In another clinical study, titled “Comparative Cytotoxicity Of Nanosilver In Human
Liver Hepg2 And Colon Caco2 Cells In Culture,” and published in the Journal of Applied
Technology in February 2014, the researchers treated human liver HepG2 cells (i.e.,
liver cancer cells) and human colon Caco2 cells (i.e., colorectal colon cancer cells) with
silver nanoparticles with an average size of 20.4 nm in order to evaluate their toxicity
to the cells.
The researchers found significant toxicity to both cancer cell lines, but at different
concentrations, with the colorectal (colon) cancer cells requiring a concentration of
silver nanoparticles 10 times higher than the liver cancer cells.
In this case, the researchers were doing something I’ve long railed against, i.e., rather
than using healthy human cell lines to test silver’s toxicity to human cells, they were
using cancer cell lines.
This is problematic, because you can’t extrapolate the potential toxicity of silver to
healthy human cells by testing them on cancerous cells. That’s because silver has an
affinity for cancer cells, i.e., it seems to target them and cause them to commit cellular
suicide (apoptosis), while leaving surrounding healthy human cells without harm.
To their credit, the authors of the above study more or less admitted this, stating:
“The HepG2 and Caco2 cells used this study appear to be targets for silver nanoparticles.
The results of this study suggest that the differences in the mechanisms of toxicity induced
by nanosilver may be largely as a consequence of the type of cells used.
This differential rather than universal response of different cell types exposed to
nanoparticles may play an important role in the mechanism of their toxicity.”
In other words, cancer cells turn out to be far more sensitive to the cytotoxic effects of
silver nanoparticles, with some types of cancer cells being more sensitive to others.
The researchers concluded: “The mitochondrial injury in HepG2 cells was significant in
the concentration range of 1 to 20 μgml(-1), but in Caco2 cells it was significant at a
higher concentration range of 10 to 20 μgml(-1).”
In short, the silver nanoparticles were demonstrated to be toxic against the liver
cancer cells at concentrations between 1ppb to 2 ppm, whereas they were toxic
against the colon cancer cells at concentrations between 1 to 2 ppm.
Note the exceedingly small concentrations, which would be very similar to conditions
in the human body after ingesting a higher concentration. The human body would
dilute the silver to a similar or lower concentration depending upon the individual’s
body volume, mass (weight), and the quantity of blood and interstitial fluids present.
A Seventh Clinical Study
In this clinical study, titled “Novel Trend in Colon Cancer Therapy Using Silver
Nanoparticles Synthesized by Honey Bee” and published in February 2015 in
the Journal of Nanomedicine & Nanotechnology, researches synthesized silver
nanoparticles using an extract from dead honey bees (talk about creating a “novel”
way of making silver nanoparticles, this one has to take the cake!).
“In the current study, the novelty in the biosynthesis of silver nanoparticles (AgNPs) using
honey bee extract has been explained.
This study was also aiming at investigating the anti-colon cancer activities of the biogenic
AgNPs along with its capping biomolecules in vitro.
… it was found that both AgNPs and its capping biomolecules have anti-proliferative
effects with a priority to the naked AgNPs.”
In other words, the researchers found that both the “biomolecules” (i.e., the honey
bee extract) and the silver nanoparticles stopped the colon cancer cells from growing
(i.e., “anti-proliferative effects”). But the silver nanoparticles had the most profound
anti-cancer effects.
The researchers concluded their study by stating:
“This study reports that 12-18 nm sized biogenic AgNPs have been successfully synthesized
using honey bee extract as a novel reducing agent.
Both the obtained AgNPs and their capping biomolecules showed anti-colon cancer
activities at both cellular and molecular levels comparing with 5 FU.
In conclusion, the single-step and ecofriendly synthesized AgNPs could be a promising
agent in colon cancer therapy or drug delivery.”
So once again we see researchers working to create “novel” forms of silver
nanoparticles — in this case, silver nanoparticles capped with an extract from dead
honey bees — so they can patent the end result and turn it into a viable drug. And we
further see that colon cancer cells are indeed susceptible to the silver treatment.
A Eighth Clinical Study
Another interesting clinical study, titled “In Vitro Anticancer Activity of Au, Ag
Nanoparticles Synthesized Using Commelina nudiflora L. Aqueous Extract Against HCT-
116 Colon Cancer Cells,” was published in the journal Biological Trace Element
Research in March 2016.
In this study, researchers tested both gold and silver nanoparticles against HCT-116
colon cancer cells, and found that both types of nanoparticles demonstrated “reduced
cell viability and increased cytotoxicity at concentrations of 200 ppm and 100 ppm
respectively.”
In other words, colon cancer cells began to die when exposed to gold nanoparticles at
200 ppm and silver nanoparticles at 100 ppm.
The researchers concluded “Overall, these findings have proved that the synthesized gold
and silver nanoparticles could be potent anti-colon cancer drugs.”
A Ninth Clinical Study
In another clinical study, this one titled “Cytotoxic Potential and Molecular Pathway
Analysis of Silver Nanoparticles in Human Colon Cancer Cells HCT116” and published
in the International Journal of Molecular Sciences in August 2018, researchers confirmed
that relatively low concentrations of silver nanoparticles caused colon cancer cells to
die.
The researchers wrote:
“Cytotoxicity assays indicated that the AgNPs in HCT116 colorectal cancer cells were very
effective at low concentrations. The viability and proliferation of colon cancer cells treated
with 5 µg/mL biogenic AgNPs were reduced by 50%.”
In other words, silver nanoparticles (i.e., AgNPs) used against colon cancer cells in a
concentration of only 5 ppm reduced the viability of the cancer cells by 50%.
The researchers further wrote:
“Thus, the AgNP tumor suppressive effects were mediated by cell apoptosis following DNA
damage, as well as by mitochondrial dysfunction and cell-cycle arrest following aberrant
regulation of p53 effector proteins.”
Stated in plain English, the silver nanoparticles worked by causing the colon cancer
cells to commit cellular suicide (i.e., apoptosis).
The apoptosis was caused when the silver nanoparticles came into contact with the
colon cancer cells, damaged their DNA and caused the energy-producing portion of
the cells (mitochondria) to malfunction, ultimately resulting in cell death.
The researchers summed up their study by stating:
“The human HCT116 cell line was exposed to 2–10 μg/mL AgNPs (6 nm) for 24 h followed by
various cellular assays and RNA-Seq analysis.
To determine the potential anti-cancer effect of AgNPs, we synthesized AgNPs using
naringenin, which is a flavonoid predominantly found in grapefruit.
HCT116 cells exposed to AgNPs for 24 h exhibited significant loss of cell viability and
proliferation in a dose-dependent manner.
The 50% inhibitory concentrations of 5 µg/mL AgNPs remarkably increased LDH leakage,
ROS generation, and MDA levels, and decreased dead-cell protease activity levels and ATP
generation.
These events led to cell death by impairing mitochondrial function and by inducing DNA
damage.”
Put another way, silver nanoparticles were synthesized using a grapefruit extract
known as naringenin (making it easy for researchers to patent the product as a “drug,”
because of the novel method of manufacturing the silver nanoparticles).
And when the colon cancer cells were exposed to concentrations of these silver
nanoparticles between 2 ppm to 10 ppm in concentration, the DNA of the cancer cells
was damaged (resulting in lower cancer cell proliferation), and the mitochondrial
function of the cancer cells was impaired.
What’s more, at 5 ppm concentration of silver nanoparticles, 50% inhibition of the
colon cancer cells was achieved — all of this in 24 hours!
A 10th Clinical Study
In a clinical study titled “Antitumor Activity of Silver Nanoparticles and Alpha-Lipoic
Acid Combinations in Colorectal Cancer Induced Experimentally,” published in April
2018 in the journal Pharmacophore, researchers chemically-induced colorectal colon
cancer tumors in 40 adult male albino wister rats, and had 10 more non-cancerous
rats as controls.
They then divided the rats up into five groups:
1. negative control (non-cancerous rats)
2. positive control (cancer-induced rats)
3. cancer-induced rats treated daily with 0.5 mg/ml silver nanoparticles orally for
two weeks after cancer induction
4. cancer-induced rats treated daily with Alpha-Lipoic Acid (60 mg/kg of body
weight) for 2 weeks after colon cancer induction. Alpha-Lipoic Acid
5. cancer-induced rats treated for two weeks after cancer induction with a
combination of silver nanoparticles and Alpha-Lipoic Acid
After the two-week period was up, the rats were killed and their blood samples
studied for cancer markers.
The researchers found that groups of rats treated with silver nanoparticles, Alpha-
Lipoic Acid and a combination of silver nanoparticles and Alpha-Lipoic Acid all
demonstrated significant amelioration (reduction) of biological markers of the
chemically-induced cancer, compared to the negative and positive control groups.
The researchers stated:
“On administering silver nanoparticles, alpha lipoic acid and their combination, colon
cancer biomarkers CEA and CCSA4 levels steadily returned to near normal.
CRC rats were treated with silver nanoparticles, alpha lipoic acid and their combination
showed a significant reduction in TNF α, TGF β and CRP.
The silver nanoparticles had a pronounced effect on inhibited pro inflammatory cytokine.
… The present study revealed significant upregulation in the gene expression level of K-RAS
in colon tissue of colorectal cancer induced rats.
…Treatment with silver nanoparticles in colorectal cancer induced rats led to significant
reduction in KRAS gene expression level in colon tissue as shown in the current data.
The suggested mechanism for the inhibition of k-RAS gene expression level due to treatment
with silver nanoparticles in colon cancer-induced rats is the ability of silver nanoparticles to
suppress the activation of Akt and Erk.”
In plain English, the major cancer markers all diminished when the cancer-induced
rats were treated with silver nanoparticles, Alpha-Lipoic Acid, or a combination of the
two.
The researchers concluded:
“Based on our results, it could be concluded that silver nanoparticles plus ALA has a
promising therapeutic role against colorectal cancer induced by 1,2 dimethylhydrazine as
indicated by the observed improvement in the measured histological, molecular and
biochemical markers.
These effects achieved through the powerful anti-inflammatory properties [of silver
nanoparticles and of Alpha-Lipoic Acid]. These results represented good therapeutic
approaches for intervention against progressive of colorectal cancer with special reference
to the inflammatory response.”
Once again we see that colon cancer — this time colon cancer tumors induced in rats,
rather than colon cancer cell lines in a test tube — is susceptible to silver
nanoparticles.
An 11th Clinical Study
In another study, titled “Thermal Co-Reduction Engineered Silver Nanoparticles Induce
Oxidative Cell Damage In Human Colon Cancer Cells Through Inhibition Of Reduced
Glutathione And Induction Of Mitochondria-Involved Apoptosis,” published in
November 2018 in the journal Chemico-Biological Interactions, the researchers wrote:
“In this study, we report the detailed toxicological analysis of AgNPs fabricated by thermal
co-reduction approach [i.e., another “novel” way of manufacturing silver nanoparticles
so they can be patented as “drugs” — ED] in human colon cancer cell line (HCT 116).”
The researchers go on to state that:
“It was also observed that AgNP induces oxidative stress on HCT116 by increased levels of
lipid peroxidation and reduced levels of glutathione.”
In other words, like the other studies above, the silver nanoparticles were found to
induce higher levels of reactive oxygen species upon contact with cancerous cells,
resulting in damage to the unhealthy cells. The researchers further state:
“Mitochondrial membrane depolarization was also analysed and Western blot analysis
confirms the increased level of Bcl and Caspase-3 which indicates the mitochondrial-
mediated apoptosis. Additionally, flow cytometric analysis suggests cell cycle arrest in G2/M
phase.”
In plain English, like the other studies, this study demonstrated that silver causes the
cancer cells to kill themselves through the process called apoptosis.
Yes, a 12th Clinical Study
Yet another clinical study was published in April 2017 in the journal Artificial Cells,
Nanomedicine, and Biotechnology. It was titled “Green Synthesis of Silver Nanoparticles
Using Anthemis Atropatana Extract: Characterization and In Vitro Biological Activities.”
According to the researchers:
“[Previous] studies have indicated good potential of AgNPs as anticancer and antibacterial
agent. AgNPs destroy the mitochondrial respiration chain in cancer cells as well as
degrading DNA, which ultimately results in cancer cells death.
“This study aim to synthesize silver nanoparticles (AgNPs) using Anthemis
atropatana extract and to evaluate their chemical characteristics and antimicrobial and
cytotoxic effects.
…In biological tests, the MTT results indicate the dose dependence of cytotoxic effects of
AgNPs on colon cancer cell lines (HT29).
The AgNPs had maximum cytotoxicity on HT29 cancer cell line at 100 μg/ml concentration,
which were statistically significant comparing control cells (p < .001).
Moreover, real time PCR and flow cytometry results confirmed the apoptotic effects of
AgNPs.
According to the results, it seems that the green synthesis of AgNPs is an eco-friendly and
cost effective approach. This research provides insight into the development of new
anticancer and antibacterial agents.”
In a nutshell, silver nanoparticles
synthesized using a plant extract
native to Iran were tested against
colon cancer cell line HT29, and
were found to be most toxic to the
cancer cells at 100 ppm.
The following chart from the study
shows the control cancer cells (i.e.,
no treatment) on the far right. At
3.25 ppm silver nanoparticles,
there was a more than 20%
reduction in cancer cell survival. At
6.25 ppm silver nanoparticles,
there was nearly a 50% reduction.
At 12.5 ppm silver nanoparticles
there was a near 60% reduction. At 25 ppm there was a near 80% reduction. At 50
ppm there was a near 90% reduction. And at 100 ppm there was close to 95%
reduction in cancer cell survival.

The researchers concluded:

“In this study, A. atropatana extract was used for the first time as a reducing and capping
agent to synthesize AgNPs without production of any harmful chemicals.
… the AgNPs had antibacterial and anticancer effects and it can induce the apoptosis more
intensely than necrosis [i.e., death from cell injury — ED] in cancer cell line.
According to significant biological effects of the synthesized AgNPs, it suggested that further
studies were performed for AgNPs pharmaceutical importance.”
In short, silver nanoparticles were demonstrated to be both antibacterial and have
anti-cancer effects against the colon cancer cell line tested.
More Studies
At the time of this writing, there are probably close to a dozen more studies
demonstrating that silver nanoparticles are effective cytotoxic agents against colon
cancer.
There may even be more than that available. Indeed, the more I looked, online, the
more I continued to find. But for the sake of brevity, I chose to limit this discussion to
the 12 studies summarized above.
It’s important to note that with the exception of the rat study (see study #10 above)
these studies are all in vitro studies (i.e., lab “test tube” studies). This means there’s a
decided lack of animal and human studies. All that’s been proven so far, essentially, is
that in the lab silver nanoparticles kill colon cancer cells quite handily.
That, of course, is a far cry from claiming that silver nanoparticles are an effective
cancer treatment in humans or animals.
But these preliminary “test tube” studies — whose number continues to grow —
should at some point in time spur researchers to do further animal studies, followed
by human studies.
Until then, we won’t know what an appropriate dosage of silver would be, in terms of
treating colon cancer in humans with colloidal silver or any other form of silver. Nor
do we know what the proper method of administration should be for maximum
effectiveness. So I, for one, look forward to more studies to come.
It’s quite exciting to see that researchers from around the world are looking into the
anti-cancer effects of silver nanoparticles against colon cancer — one of the most
deadly of all cancers.
And because these studies add to the plethora of studies demonstrating silver to be
effective against numerous forms of cancer (50 of which studies are documented in
my 126 page book, Colloidal Silver and Cancer: a Surprising Look), it all points to an
exciting future in which silver might become one of the safest and most effective
cancer treatments the world has ever known.