Tumor & Metastasis Inhibitors

Tumor & Metastasis Inhibitors

 

Around 90% of cancer deaths are as a result of metastasis (cancer spreading to other organs). Cancer stem cells are suspected to be the cause of most – if not all – metastases.

Standard cancer treatments are unable to kill cancer stem cells, so the tumor grows back in many cases (often with a vexing resistance to the previously used therapy).

The Stem Cell Theory of Cancer
Source: Ludwig Center, Stanford Medicine
Research has shown that cancer cells are not all the same. Within a malignant tumor or among the circulating cancerous cells of a leukemia, there can be a variety of types of cells.

The stem cell theory of cancer proposes that among all cancerous cells, a few act as stem cells that reproduce themselves and sustain the cancer, much like normal stem cells normally renew and sustain our organs and tissues. In this view, cancer cells that are not stem cells can cause problems, but they cannot sustain an attack on our bodies over the long term.

The idea that cancer is primarily driven by a smaller population of stem cells has important implications. For instance, many new anti-cancer therapies are evaluated based on their ability to shrink tumors, but if the therapies are not killing the cancer stem cells, the tumor will soon grow back (often with a vexing resistance to the previously used therapy). An analogy would be a weeding technique that is evaluated based on how low it can chop the weed stalks—but no matter how low the weeds are cut, if the roots aren’t taken out, the weeds will just grow back.

Food and Cancer Stem Cells
A new scientific review confirms conventional therapeutics including chemotherapy and radiation therapy exhibit poor performance against Cancer Stem Cells (CSCs), leading to tumor regrowth and metastasis. Many natural products, including those found in common foodstuffs have demonstrated the ability to modulate pathways responsible for Cancer Stem Cells function and inhibition.

Importantly, emerging evidence strongly suggests that diet is a major modulator of the epigenetic state of cells and is able to reverse abnormal or altered gene expression patterns, according to this review

Certain Foods can kill Cancer Stem Cells
Many natural products, including those found in common foodstuffs have demonstrated the ability to modulate pathways responsible for Cancer Stem Cells function and inhibition. Some supplements and a few non-cancer drugs can also kill these stem cells.

Here is a list of these products, followed by a look at the scientifis evidence supporting their efficacy.

Foods that kill Cancer Stem Cells

(EGCG)
Green Tea
Vitamin D
Sunshine, fish, beef liver, cheese, yogurt
B-carotine
Leafy green vegetables, carrots, sweet potatoes, peas,
Curcumin
Turmeric
Resveratrol
Grapes, berries, plums
Genistein
Soybeans and Soy protein
Quercetin
Onions, Capers, Doc leaves (raw), Lovage (sea parsley)
Sulphoraphane
Cruciferous vegetables eg broccoli, Sprouts, cabbages, cauliflower
Lycopene
Tomatoes, watermelon, papaya, pink grapefruit
Blueberries
Piperine
Black pepper
Vitamin C (Ascorbic acid)
Indole-3-Carbinol (I3C)
Cabbage, brussels sprouts, cauliflower, radishes, and broccoli
Gingerols
Ginger
Falcarinol and falcarindiol
Polyacetylenes derived from carrot and parsley
Ursolic acid
Apples, basil, bilberries, cranberries, elder flower, peppermint
Anthocyanins
Purple Potatoes
Apigenin
Parsley, thyme, chamomile and red pepper

Supplements that kill Cancer Stem Cells

CAPE
Antioxidant extracted from honeybee hive (bee glue)
Withaferin A
Ashwagandha
Silibinin
Milk Thistle seed extract
Berberine
Feverfew and Green chirayta (Andrographis Paniculata)

Drugs that kill Cancer Stem Cells

Doxycycline (an antibiotic)
Metformin (diabetes drug)
Stiripentol (epilepsy drug)
Salinomycin (anti-biotic drug)

Prolongs Survival Time

Cesium Chloride
Avemar
Homeopathy
Cimetidine (Tagamet) (antihistamine)
Melatonin (hormonal supplement)
Metformin (diabetes drug)

Reduces Metastatis

Avemar (fermented wheat germ extract)
Aspirin

Sodium Bicarbonate
Chloroquine (malaris drug)

Inhibits Tumor Growth

Naringenin (found in citrus fruits)

Hesperiden (found in citrus fruits)
Artemesinin
Magnet therapy

A look at some of the science supporting these benefits.

Green Tea (EGCG)
According to this study, numerous reports have shown the ability of EGCG to specifically modulate cancer stem cells in a variety of cancer types. EGCG inhibited colorectal cancer stem cells.

Vitamin D
Sunshine spurs the body to make vitamin D.

Food sources: Fish such as salmon, tuna, and mackerel. Small amounts of vitamin D are found in beef liver, cheese, and egg yolks.
This study says Vitamin D and its analogs have inhibitory effects on cancer stem cell signaling in various types of human cancer cells and may be promising therapeutic/preventive agents against Cancer Stem Cells.
This study concluded: Vitamin D plays a pivotal role in Gastrointestinal Tract malignancies. Vitamin D affects several cellular mechanisms such as inhibiting differentiation, proliferation, metastasis and invasion, angiogenesis, inducing cell cycle arrest, and apoptosis, thus supporting its anticancer role.

This study says: Several lines of evidence have demonstrated that vitamin D plays an important role in the regulation of stem cells of the prostate and the skin. Moreover, vitamin D is a well known inducer of the terminal differentiation of human myeloid leukemia cells… Recently, vitamin D and its analogs were shown to reduce the number of CSCs in breast cancer, further supporting their potential as therapeutic agents.
More about Vitamin D

B-carotine
Food sources: Leafy green vegetables, carrots, sweet potatoes, peas, green bell peppers, avacado, and kiwi

Exhibits excellent anti-Cancer Stem Cell qualities according to this study
Also available in Supplement form.

Curcumin
Food sources: Turmeric

Has been shown to exhibit cytotoxic effects on Cancer Stem Cells and selectively targets CSC in Esophageal squamous carcinoma according to this Study

Resveratrol
Food sources: Grapes, berries, plums

This Study says Resveratrol may be able to eliminate Cancer Stem Cell populations from tumors.
Resveratrol affects all three discrete stages of carcinogenesis (initiation, promotion, and progression)

Genistein
Food sources: Soybeans and Soy protein
Inhibits ovarian cancer stem cells says this
study

Quercetin
Food sources: Onions, Capers, Doc leaves (raw), Lovage (sea parsley), Dill weed.
Has been demonstrated to induce programmed cell death in many
malignant cancer cell lines…a potential cancer stem cell targeting therapeutic, says this study

Sulphoraphane
Food sources: Cruciferous vegetables eg broccoli, Sprouts, cabbages, cauliflower
Shown to target breast cancer stem cells according to this
study

Lycopene (phytochemical)
Food sources: Tomatoes, watermelon, papaya, pink grapefruit
In this review, the authors highlight the remarkable ability of phytochemicals to decrease the replicative capacity of Cancer Stem Cells…These phytochemicals have been thoroughly studied for at least three decades…these studies provide a huge body of knowledge, which can now be applied in the development of treatments against CSCs.

This study says Lycopene has been shown to induce apoptosis and inhibit cell cycle progression in various cancer cells.

A combination of vitamin E, selenium, and lycopene has been shown to dramatically inhibit prostate cancer development and to increase disease-free survival. Lycopene has also been shown to suppress the growth of lung cancer cells, according to this study

This article says an epidemiological study in elderly Americans indicated that high tomato intake was associated with a 50% reduction in mortality from cancers at all sites,

 

Blueberries
Suppresses the generation of breast cancer stem cells according to this study, while this study says it inhibits the proliferation of melanoma cells.

Piperine
Food sources: Black Pepper
The treatment of colon cancer cells with piperine has been shown to reduce the ability of the cells
to form non-adherent spheres and colonies, suggesting the inhibiting effect of piperine on cancer stem cells, says this study

Vitamin C (Ascorbic acid)
Mainly high doses used for cancer – oral or intravenous.
Food Sources:
small amounts in oranges, orange juice, red pepper, tomatoes and tomato juice, citrus fruits

Data in this study suggest that high-dose Vitamin C selectively induces DNA damage on cancer stem cells.
This study revealed that Vitamin C treatment dramatically reduced the self-renewal ability, and percentages of Cancer Stem Cells in Liver cancer.
This study found that Vitamin C was 10 times more potent than anticancer drug 2-DG for the targeting of Cancer Stem Cells.
This study
says Vitamin D and its analogs have inhibitory effects on cancer stem cell signaling in various types of human cancer cells.

Indole-3-Carbinol (I3C)
Food sources: vegetables such as cabbage, brussels sprouts, cauliflower, radishes, and broccoli
Also available as a Supplement
The authors of this research paper say previous studies have shown that I3C inhibits prostate cancer cell growth and prevent or delay the progression of cancer, through its ability to attack cancer stem cells

I3C has a widespread effect on multiple cancer cells, such as breast cancer, melanoma, and prostate cancers, according to this study. This demonstrates the I3C plays a significant role in either the cell cycle arrest or apoptosis of various cancers.

Gingerols
Food sources: Ginger
This study says growth arrest and apoptosis of human colorectal cancer cells treated with 6-gingerol,
was shown to occur.

Falcarinol and falcarindiol
Polyacetylenes derived from carrot and parsley
The authors of this study say they provide several pieces of evidence suggesting that falcarindiol has the anticancer role by targeting glioblastoma cells, as well as glioblastoma stem-like cells. Falcarindiol was shown to selectively kill colorectal cancer cells and repress tumor growth, without affecting normal colon epithelial cells. The anticancer function of falcarindiol was further demonstrated with breast cancer cells in which falcarindiol contributed to autophagy-dependent tumor cell death.
This study says falcarindiol inhibits development of breast and other cancers.

Ursolic acid
Food sources: apples, basil, bilberries, cranberries, elder flower, peppermint, rosemary, lavender, oregano, thyme, hawthorn, prunes
Also available as a Supplement
Findings suggested that UA is involved in mechanism to affect the proliferation and apoptosis of human ovarian cancer stem-like cells and it is a potent anti-ovarian cancer agent, according to this
study

Anthocyanins (Purple Potatoes)
Baked purple-fleshed potato suppressed proliferation and induced apoptosis in colon cancer stem cells, says this study.
The study authors say their results provide the evidence that Purple Potato extract has the potential to target the self-renewal of colon cancer stem cells.

Apigenin
Food sources: parsley, thyme, chamomile and red pepper
These results indicate that the flavonoids, particularly apigenin and quercetin, can reduce theself-renewal capacity of Glioblastoma stem-like cells. These findings underscore the therapeutic potential of the flavonoids to suppress Glioblastoma metastasis by regulating the migration and invasion of Glioblastoma Stem Cells, according to this study

Supplements that kill Cancer Stem Cells

CAPE (antioxidant extracted from honeybee hive – bee glue)
The authors of this study showed that CAPE inhibits the growth of breast cancer stem cells and potentially makes them more susceptible to chemotherapeutic agents when used in combination.

The authors of this study say their results strongly suggest that CAPE could be a powerful inhibitor of cancer stem cell growth and functions that are responsible for CSC-mediated recurrence of breast cancer and increased patient mortality.

This scientific review says that recent studies indicate that CAPE (caffeic acid phenethyl ester ) treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells… CAPE treatment will be useful for treatment of advanced oral cancer patients.

Withaferin A (Ashwagandha)
The herbal supplement Withaferin A significantly inhibited the tumorigenic potential of isolated cancer stem cells in vitro and significantly reduced its expression in tumors collected from mice, according to this Study

This study says Withaferin A induces cell death (apoptosis/necrosis) in multiple types of tumor cells.

Silibinin (Milk Thistle seed extract)
Recent preclinical studies have shown strong efficacy of silibinin to target cancer cell’s migratory and invasive characteristics as well as their ability to metastasize to distant organs, according to this study

The authors of this study say their data provide sufficient evidence that silibinin has dual efficacy against both bulk colorectal cancer cells cells and colon cancer stem cells.

Berberine
Berberine
is an alkaloid isolated from the roots and bark of Berberis plants and is available as a supplement.
This study showed the anti-cancer stem cell effect of berberine on oral cancer.

Feverfew and Green chirayta (Andrographis Paniculata)
This review says “the compound parthenolide, which is derived from the medicinal plant feverfew, has recently been shown to preferentially induce acute myelogenous leukaemia (AML) stem cells to undergo apoptosis. Importantly, parthenolide had no discernable effect on normal blood cells.”

This study shows that feverfew plant extract and Green chirayta plant extract are highly effective anti-myeloma cancer stem cell agents, with Green chirayta plant extract displaying increased selectivity for myeloma cancer stem cells compared to feverfew plant extract. The data presented here constitute the first report of natural products with anti-Cancer Stem Cell activity in myeloma cancer

 

Drugs that kill Cancer Stem Cells
Doxycycline
This study found that antibiotics, such as Doxycycline, could eradicate Cancer Stem Cells in multiple cancer types. These include: DCIS, breast (ER(+) and ER(-)), ovarian, prostate, lung, and pancreatic carcinomas, as well as melanoma and glioblastoma. Doxycycline was also effective in halting the propagation of primary cultures of CSCs from breast cancer patients, with advanced metastatic disease. The study authors propose the combined use of Doxycycline and Vitamin C as a new strategy for eradicating CSCs.

Doxycycline and Vitamin C
This study found that a combination of Doxycycline (an anti-biotic) and Vitamin C could eradicate Cancer Stem Cells in a number of cancer types. The authors state:
“it became apparent that tetracycline antibiotics, such as Doxycycline, could be re-purposed to eradicate CSCs, in multiple cancer types. These eight distinct cancer types included: DCIS, breast (ER(+) and ER(−)), ovarian, prostate, lung, and pancreatic carcinomas, as well as melanoma and glioblastoma.
Doxycycline was also effective in halting the propagation of primary cultures of CSCs from breast cancer patients, with advanced metastatic disease …”

Metformin (type 2 diabetes drug)
In human cancer cells of different origin, metformin has been shown to induce cell cycle arrest, growth inhibition and apoptosis…As demonstrated in a number of recent studies,
metformin is able to selectively target Cancer Stem Cells in different types of human cancers, including breast , pancreatic and thyroid cancer. In particular, metformin has been shown to selectively kill Cancer Stem Cells in four genetically different types of human breast cancer, according to this study

Stiripentol – an epilepsy treatment drug
This study found that stiripentol was between 50 to 100 times more potent than anticancer drug 2-DG in targeting Cancer Stem Cells.

Salinomycin (anti-biotic drug)
Salinomycin has been shown to inhibit oxidative phosphorylation in mitochondria that may contribute to the elimination of Cancer Stem Cells by salinomycin, says this study

This study says salinomycin reduces the proportion of Cancer Stem Cells by more than 100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug…salinomycin preferentially targets the viability of CSCs within breast cancer cell populations.

Prolongs Survival Time

Cesium Chloride
This study reports on 50 patients treated with Cesium. An impressive 50% recovered from various cancers, i.e., cancer of unknown primary, breast, colon, prostate, pancrease, lung, liver, lymphoma, ewing sarcoma of the pelvis and adeno-cancer of the gallbladder. A consistent finding in these patients was the disappearance of pain within the initial 3 days of Cs-treatment.

Avemar
Avemar is an all-natural, clinically proven, dietary supplement for cancer patients. Medical experts recognize Avemar as an effective supportive cancer treatment and recommend complementing the diet of concerned patients with Avemar.

Cimetidine (Tagamet)
Researchers have discovered antihistamines used to treat allergy have unique anti-cancer properties that are just now being recognized. It has been shown that the drug stops cancer cells being ´sticky´ and clumping together or sticking to organs and this could prevent new tumours forming and new metastatic spread. It is particularly useful shortly before, during and after surgery to stop any threat of spread. In 2002 Clinical Trials of people having Colorectal surgery, 47 per cent did not survive 3 years. But with those taking Cimetidine, this figure fell to just 5 per cent. Swedish research showed that women with breast cancer who were coincidentally taking anti-histamines (such as Desloratidine or Loratidine) survived up to 50 per cent longer than those who weren´t.
There is some concern that Cimetidine has estrogenic properties. If you have breast cancer or prostate cancer, for example, this may be a concern.

Melatonin
Melatonin is a hormonal supplement of synthetic origin, but occasionally derived from animal sources. Melatonin is produced naturally in the body. Current evidence indicates that supplemental melatonin may positively influence tumor remission and survival of cancer patients, as well as protecting against side effects from anticancer treatment.

Metformin
Metformin, a drug used with Type-2 diabetes to lower serum glucose levels has been shown to be extremely helpful in cancer treatment. A meta-analysis of 20 research papers by Dr. Ming Yin et al in The Oncologist stated the metformin helped ‘increase survival times of patients’. Diabetics who take metformin are much less likely to develop cancer than those who don’t.

Homeopathy

This study published in INTERNATIONAL JOURNAL OF ONCOLOGY involved15 patients (9 male, 6 female) with intracranial brain cancers who were treated with Ruta 6 and Ca3(PO4)2 at the PBH Research Foundation, Kolkata, India, had been diagnosed with glioma (9 patients), meningioma (3 patients), crainio-pharyngioma (1 patient), neurinoma (1 patient), and pituitary tumors (1 patient).

The combination therapy of Ruta 6 and Ca3(PO4)2 was very effective in the treatment of intracranial brain cancers. Of the 9 patients with glioma, 8 (88.9%) showed complete regression, and the other patient showed partial regression. Two of the three patients with meningioma showed prolonged arrest of their tumors and the third had complete regression. The one patient with craniopharyngioma and the one patient with pituitary tumors both showed complete regression, and the 1 patient with neurinoma has had prolonged arrest of her tumor as determined by computed tomographic scan images.

The study was a collaboration between the Departments of Cancer Biology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center,Houston, Texas and PBH Research Foundation, West Bengal, India.

 

Reduces Metastatis

Avemar
Avemar, a derivative of fermented wheat germ extract, is a non-toxic and natural compound that is used as a dietary supplement by cancer patients undergoing chemotherapy and radiotherapy. Avemar has numerous biological activities, and several recent studies have reported that it may also have metastatic and anti-angiogenic effects.

This study says the oral use of Avemar in patients with advanced colorectal cancer or high-risk melanoma inhibits the formation of tumor metastases and prolongs survival following chemotherapy and surgery.
More about Avemar.

Cesium Chloride
This study found Cesium Chloride (in addition to some vitamins, minerals, chelating agents and salts of selenium, potassium and magnesium, as well as a special diet) Improves Immune System by making cancer cells highly alkaline,  thus killing the cancer cell. Cesium chloride not only kills cancer cells, but it immediately stops the metastasis of the cancer, can shrink tumor masses within weeks, and almost always stops the pain of cancer within 12 to 36 hours.

Aspirin
A 2013 study published in PubMed concludes “data from randomised clinical studies have shown that aspirin prevents the development of malignancy, and it also appears to decrease the development and spread of metastases.

Sodium Bicarbonate (Baking Soda)
This study found that oral bicarbonate therapy significantly reduced the incidence of metastases in experimental models of breast and prostate cancer… Notably, bicarbonate did not affect the systemic pH or the growth rate of primary tumors but had significant effects on the formation of spontaneous metastases.

Chloroquine
Chloroquine, a drug currently used to treat malaria, may be useful in treating patients with metastatic cancers according to a new study by University of Kentucky Markey Cancer Center.

Inhibits Tumor Growth


Naringenin

The results of this study suggest that Naringenin, one of the most abundant flavonoids in citrus fruits, has a potentially useful inhibitory effect on tumor growth.
Available in supplement form

Hesperidin
This study says Hesperidin has been proven to be an effective medicine possessing many pharmacological activities such as antioxidant, anti-inflammatory…and inhibition of tumor promoters. Hesperidin has the potential to be developed as a chemotherapeutic or adjuvant agent for human cervical cancer.
Hesperidin is a plant chemical that is found primarily in citrus fruits such as oranges, grapefruits, and lemons.

Artemesinin

This study found that Artemisinin and its derivatives could suppress lung-tumor progression.

This study revealed experimental evidences suggesting that artemisinin compounds may be a therapeutic alternative in highly aggressive cancers with rapid dissemination, without developing drug resistance.

Magnet therapy

This study says: we report that direct exposure of mice to magnetic fields reduced tumor growth and progression. Mice exposed to magnetic fields for 360 min daily for as long as 4 wk showed extensive areas of necrosis in their tumors.


Alcohol and Cancer Stem Cells
Available evidence indicates that alcohol increases cancer stem Cell population, and therefore may promote aggressiveness, recurrence, and therapy resistance of cancers –
study

Main studies
The use of natural products to target cancer stem cells

Natural Products That Target Cancer Stem Cells

Implications of Cancer Stem Cell Theory for Cancer Chemoprevention by Natural Dietary Compounds

Phytochemicals as Innovative Therapeutic Tools against Cancer Stem Cells

The primary reason why conventional chemotherapy and radiotherapy have failed to produce any significant improvements in cancer survival rates is because cancer stem cells are resistant to these interventions. In fact, chemotherapy and especially radiation are both capable of increasing the number and virulence of these cells in a tumor, while at the same time having the well-known side effect of further damaging the patient’s immune system.
Sayer Ji,
GreenmedInfo

Caution
1. Some cancer therapies can conflict with others. Do not start ANY therapy without consulting your doctor to ensure it’s safe and beneficial to do so.
2. Just because any given therapy worked for someone else does not necessarily mean it will work for you.
3. Although there are many viable cancer treatments, there isn’t a “best” treatment for a certain type or stage of cancer.

 

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