CONFIRMED: Quercetin-tocotrienols combination combats cancer


Image: CONFIRMED: Quercetin-tocotrienols combination combats cancer

The battle against cancer is heading into new territory, as scientists explore the healing ability of substances that support the body’s cells, instead of killing them off. Researchers from the Italian National Institute of Health and Science on Aging (INRCA) have made a breakthrough discovery for preventing the spread of malignant tumors. A natural plant-based combination, including quercetin and tocotrienols, effectively targets aging cells that cause chronic inflammation and cancer. This dynamic, anti-cancer duo causes stubborn cancer cells to die off and simultaneously promotes the growth of normal cells.

This dynamic duo heals the body at the cellular level by triggering a die-off sequence within aging and malignant cells. If old, decrepit cells become inefficient at performing cellular division, new cells cannot be created. If these senile cells refuse to die off, a condition called cellular senescence sets in. This causes an accumulation of aged cells that emit pro-inflammatory chemicals into the body. This process promotes aging in the body and increases cancer risk. Quercetin and tocotrienols help to remove aging cells so healthy cells have space to flourish.

Moreover, quercetin and tocotrienols identify malignant cancer cells and speed up their cellular senescence. This dynamic duo effectively target unwanted cancer cells and speed up their death, preventing cancer cell replication. The two natural substances remove inflammatory, aging cells and stop malignant cells from growing. This combination is a highly intelligent form of medicine that deciphers dangerous cells and manipulates cellular senescence so that the body can heal itself. The combination can be employed as an adjunct therapy for cancers of many origins. This combination can be used to prevent cancer from taking hold and stop early cancers in their tracks.

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Anti-cancer intelligence of tocotrienols

Tocotrienols are an anti-inflammatory type of vitamin E that can be found in wheat germ, barley, oat, rye, cranberries, blueberries, kiwi, plum, coconut, and some nuts. It is also isolated in supplement form. Research confirms that this form of vitamin E can reverse cell cycle arrest and reduce DNA damage, especially for treatment of breast cancer, pancreatic cancer, and melanoma. However, assimilation of tocotrienols in the human intestine is poor because they are lipophilic in nature (they dissolve in lipids and fats). Researchers must find ways to increase the bio-availability of tocotrienols to increase this vitamin’s therapeutic effects. Intestinal absorption depends upon the secretion of bile and transporters such as ?-tocopherol transfer protein (?-TTP); therefore, assimilation of tocotrienols occurs more readily with food. Nutritionists recommend a daily dose of 150 mg of tocotrienols. One should expect to see therapeutic benefits with supplementation after ninety days.

The healing nature of quercetin

Quercetin is a plant-based flavonoid and antioxidant that helps plants defend against disease. When quercetin is combined with tocotrienols, synergy is created; together these natural substances slow the aging process, prolong the life of healthy cells, and induce apoptosis of malignant cancer cells. Because of its anti-inflammatory properties, quercetin can benefit seasonal allergies, asthma, bronchitis, and congestion. Quercetin is commonly found in apples, tea, onions, nuts, berries, cauliflower and cabbage and can be isolated and consumed in the form of a supplement. To rid the body of aging cells, nutritionists recommend a daily dose of quercetin (500 to 800 mg) for up to three consecutive months, followed by a maintenance dose of 150 mg a day. It is best to consult a healthcare professional, as many medications can adversely interact with the body when healing substances are introduced.

Sources include:

NaturalHealth365.com

NCBI.NLM.NIH.gov

NaturalPedia.com

NaturalPedia.com

Pharmacology.Imed.Pub

Role of the tumor microenvironment in regulating apoptosis and cancer progression


Highlights

  • The impairment of cell death represents the main factor of cancer outbreak, as well as the resistance to anti-cancer agents.
  • Tumor microenvironment has a critical importance in immune escape, therefore promoting tumor progression and metastasis.
  • Inflammatory responses modulate the tumor microenvironment and play a decisive role in tumor development.
  • Microenvironment-targeted therapies might be a real gain to fight cancer.

Abstract

Apoptosis is a gene-directed program that is engaged to efficiently eliminate dysfunctional cells. Evasion of apoptosis may be an important gate to tumor initiation and therapy resistance. Like any other developmental program, apoptosis can be disrupted by several genetic aberrations driving malignant cells into an uncontrolled progression and survival. For its sustained growth, cancer develops in a complex environment, which provides survival signals and rescues malignant cells from apoptosis. Recent studies have clearly shown a wide interaction between tumor cells and their microenvironment, confirming the influence of the surrounding cells on tumor expansion and invasion. These non-malignant cells not only intensify tumor cells growth but also upgrade the process of metastasis. The strong crosstalk between malignant cells and a reactive microenvironment is mediated by soluble chemokines and cytokines, which act on tumor cells through surface receptors. Disturbing the microenvironment signaling might be an encouraging approach for patient’s treatment. Therefore, the ultimate knowledge of “tumor–microenvironment” interactions facilitates the identification of novel therapeutic procedures that mobilize cancer cells from their supportive cells. This review focuses on cancer progression mediated by the dysfunction of apoptosis and by the fundamental relationship between tumor and reactive cells. New insights and valuable targets for cancer prevention and therapy are also presented.

Cell-suicide blocker holds promise as HIV therapy.


NIBSC/Science Photo Library

Immune cells (green) infected with HIV (pink) undergo a cell-suicide process known as pyroptosis.

HIV infection causes a mass suicide of immune cells — a process that can be halted by an experimental drug that blocks cellular self-destruction, studies in cell cultures suggest. Researchers are now proposing a clinical trial of the drug in people with HIV.

Current HIV therapies act by targeting key proteins made by the virus. But findings from cell cultures, published today in Science1 and Nature2, suggest that targeting proteins in host cells might be an alternative approach to preserving the immune system in the face of an HIV infection.

The papers also address a decades-old mystery: why infection-fighting immune cells die off in people with HIV. A 2010 study3 showed that HIV does not directly kill most of these cells, called CD4 cells. Instead, the cells often self-destruct. “It’s much more a suicide than it is a murder,” says Warner Greene, a molecular virologist at the Gladstone Institute of Virology and Immunology in San Francisco, California, and a co-author of both the latest works.

Ring of fire

In the latest studies, Greene’s team investigated these ‘abortive’ infections. They identified a sensor that detects viral DNA in the cell and activates the suicide response1. And they found that most of the cellular suicide occurs via a process called pyroptosis, in which the dying cells unleash a ferocious inflammatory response2. A key protein involved in pyroptosis is caspase 1, and an experimental caspase-1 inhibitor made by Vertex Pharmaceuticals in Cambridge, Massachusetts, had already been tested in humans as a potential treatment for epilepsy. The drug, VX-765, failed to help epileptics, but six-week-long studies suggested that it was safe.

Greene and his colleagues tested VX-765 in HIV-infected cells cultured from human tonsils and spleens, and found that it blocked pyroptosis, prevented CD4 cell death, and suppressed inflammation. Greene hopes that the approach could one day provide an alternative or embellishment to the antiretroviral drugs currently used by 9.7 million people worldwide to manage HIV infection.

Because a caspase-1 inhibitor would target a host protein rather than the virus, HIV is less likely to become resistant to the therapy, says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. But any new HIV therapy will face steep competition from the more than 30 antiretroviral drugs currently available. “You’ve got to be pretty good to replace the antiretrovirals,” says Fauci.

Self-sacrifice

Understanding why HIV infection kills CD4 cells is an important step for researchers, says Gary Nabel, chief scientific officer at Sanofi, a pharmaceutical company headquartered in Paris. “We need to understand when a cell would rather die than let a virus infect it, and how the virus can evade that cellular suicide response to infection,” he says.

But Nabel also urges caution. He worries that some of the infections that Greene and his team consider abortive may progress if the immune cells survive. “Preventing cell death is a double-edged sword in the context of HIV,” he says. “Death can be protective if a T cell says ‘I’m going to die before I let this virus replicate and spread to other cells.’”

Greene counters that his team looked for evidence of progression to active infection, and found none. “Pyroptosis is not a strategy to protect the host from productive infection,” says Greene. “Instead, this is a pathway that actually promotes clinical progression to AIDS.”

Senescence and aging: the critical roles of p53.


p53 functions as a transcription factor involved in cell-cycle control, DNA repair, apoptosis and cellular stress responses. However, besides inducing cell growth arrest and apoptosis, p53 activation also modulates cellular senescence and organismal aging. Senescence is an irreversible cell-cycle arrest that has a crucial role both in aging and as a robust physiological antitumor response, which counteracts oncogenic insults. Therefore, via the regulation of senescence, p53 contributes to tumor growth suppression, in a manner strictly dependent by its expression and cellular context. In this review, we focus on the recent advances on the contribution of p53 to cellular senescence and its implication for cancer therapy, and we will discuss p53’s impact on animal lifespan. Moreover, we describe p53-mediated regulation of several physiological pathways that could mediate its role in both senescence and aging.

 

Source: Oncogene

Various modes of cell death induced by DNA damage.


The consequences of DNA damage depend on the cell type and the severity of the damage. Mild DNA damage can be repaired with or without cell-cycle arrest. More severe and irreparable DNA injury leads to the appearance of cells that carry mutations or causes a shift towards induction of the senescence or cell death programs. Although for many years it was argued that DNA damage kills cells via apoptosis or necrosis, technical and methodological progress during the last few years has helped to reveal that this injury might also activate death by autophagy or mitotic catastrophe, which may then be followed by apoptosis or necrosis. The molecular basis underlying the decision-making process is currently the subject of intense investigation. Here, we review current knowledge about the response to DNA damage and subsequent signaling, with particular attention to cell death induction and the molecular switches between different cell death modalities following damage.

Source: http://www.nature.com

The dual effects of delta(9)-tetrahydrocannabinol on cholangiocarcinoma cells: anti-invasion activity at low concentration and apoptosis induction at high concentration..


Abstract

Currently, only gemcitabine plus platinum demonstrates the considerable activity for cholangiocarcinoma. The anticancer effect of Delta (9)-tetrahydrocannabinol (THC), the principal active component of cannabinoids has been demonstrated in various kinds of cancers. We therefore evaluate the antitumor effects of THC on cholangiocarcinoma cells. Both cholangiocarcinoma cell lines and surgical specimens from cholangiocarcinoma patients expressed cannabinoid receptors. THC inhibited cell proliferation, migration and invasion, and induced cell apoptosis. THC also decreased actin polymerization and reduced tumor cell survival in anoikis assay. pMEK1/2 and pAkt demonstrated the lower extent than untreated cells. Consequently, THC is potentially used to retard cholangiocarcinoma cell growth and metastasis.

Source: Pubmed

Enhancement of photodynamic therapy by 2,5-dimethyl celecoxib, a non-cyclooxygenase-2 inhibitor analog of celecoxib


Photodynamic therapy (PDT) effectiveness can be improved by employing combined modality approaches involving pharmaceuticals targeting the tumor microenvironment and/or tumor cell death pathways. In one approach, combining PDT with celecoxib improves long-term tumoricidal activity without increasing normal tissue photosensitization. However, side effects arising from the use of coxib based cyclooxygenase-2 (COX-2) inhibitors, including cardiovascular injury, decreases the clinical applications of this class of compounds. A growing number of studies demonstrate that the tumoricidal actions of coxibs such as celecoxib involve non-COX-2 mediated mechanisms. The celecoxib analog, 2,5-dimethyl celecoxib (DMC), lacks COX-2 inhibitory activity but exhibits cytotoxic properties comparable to the COX-2 inhibitor celecoxib. We compared the effectiveness of DMC and celecoxib in modulating PDT response at both the in vitro and in vivo level using a C3H/BA murine mammary carcinoma model. Both DMC and celecoxib blocked PDT induced expression of the pro-survival protein survivin, enhanced the endoplasmic reticulum stress (ERS) response of PDT, and increased both apoptosis and cytotoxicity in BA cells exposed to combination protocols. DMC enhanced the in vivo tumoricidal responsiveness of PDT without altering PGE2 levels. Our data demonstrates that DMC improved PDT by increasing apoptosis and tumoricidal activity without modulating COX-2 catalytic activity. Our results also suggest that celecoxib mediated enhancement of PDT may involve both COX-2 dependent and independent mechanisms.

Enhancement of photodynamic therapy by 2,5-dimethyl celecoxib, a non-cyclooxygenase-2 inhibitor analog of celecoxib


Photodynamic therapy (PDT) effectiveness can be improved by employing combined modality approaches involving pharmaceuticals targeting the tumor microenvironment and/or tumor cell death pathways. In one approach, combining PDT with celecoxib improves long-term tumoricidal activity without increasing normal tissue photosensitization. However, side effects arising from the use of coxib based cyclooxygenase-2 (COX-2) inhibitors, including cardiovascular injury, decreases the clinical applications of this class of compounds. A growing number of studies demonstrate that the tumoricidal actions of coxibs such as celecoxib involve non-COX-2 mediated mechanisms. The celecoxib analog, 2,5-dimethyl celecoxib (DMC), lacks COX-2 inhibitory activity but exhibits cytotoxic properties comparable to the COX-2 inhibitor celecoxib. We compared the effectiveness of DMC and celecoxib in modulating PDT response at both the in vitro and in vivo level using a C3H/BA murine mammary carcinoma model. Both DMC and celecoxib blocked PDT induced expression of the pro-survival protein survivin, enhanced the endoplasmic reticulum stress (ERS) response of PDT, and increased both apoptosis and cytotoxicity in BA cells exposed to combination protocols. DMC enhanced the in vivo tumoricidal responsiveness of PDT without altering PGE2 levels. Our data demonstrates that DMC improved PDT by increasing apoptosis and tumoricidal activity without modulating COX-2 catalytic activity. Our results also suggest that celecoxib mediated enhancement of PDT may involve both COX-2 dependent and independent mechanisms.

source: cancer letter

Licochalcone A inhibits growth of gastric cancer cells by arresting cell cycle progression and inducing apoptosis


The aim of this study was to determine the anticancer effects of seven licorice compounds in MKN-28, AGS, and MKN-45 gastric cancer cells and human gastric epithelium immortalized cells. We also explored the mechanism of action of licochalcone A (LCA), the most cytotoxic licorice compound, by analyzing its influence on cell cycle progression and apoptosis. The results indicated that LCA was the most cytotoxic licorice compound of those tested, and it inhibited gastric cancer cells growth in a dose-dependent manner, with an IC50 value of approximately 40μM. LCA affected gastric cancer cell viability by blocking cell cycle progression at the G2/M transition and inducing apoptosis. LCA treatment increased the expression of Rb and decreased the expression of cyclin A, cyclin B and MDM2 in MKN-28, AGS and MKN-45 cell lines. In addition, LCA-induced apoptosis by its effects on the expression of PARP, caspase-3, Bcl-2 and Bax. These data provide evidence that LCA has the potential to be used in the treatment of gastric cancer.

source: cancer letter