Chemoprevention

Cancer is a Preventable Disease that Requires Major Lifestyle Changes

Cancer is caused by both internal factors (such as inherited mutations, hormones, and immune conditions) and environmental/acquired factors (such as tobacco, diet, radiation, and infectious organisms). The link between diet and cancer is revealed by the large variation in rates of specific cancers in various countries and by the observed changes in the incidence of cancer in migrating. For example, Asians have been shown to have a 25 times lower incidence of prostate cancer and a ten times lower incidence of breast cancer than do residents of Western countries, and the rates for these cancers increase substantially after Asians migrate to the West.

The importance of lifestyle factors in the development of cancer was also shown in studies of onozygotic twins(8). Only 5–10% of all cancers are due to an inherited gene defect. Various cancers that have been linked to genetic defects. Although all cancers are a result of multiple mutations (9, 10), these mutations are due to interaction with the environment (11, 12). These observations indicate that most cancers are not of hereditary origin and that lifestyle factors, such as dietary habits, smoking, alcohol consumption, and infections, have a profound influence on their development (13).

Although the hereditary factors cannot be modified, the lifestyle and environmental factors are potentially modifiable. The lesser hereditary influence of cancer and the modifiable nature of the environmental factors point to the preventability of cancer. The important lifestyle factors that affect the incidence and mortality of cancer include tobacco, alcohol, diet, obesity, infectious agents, environmental pollutants, and radiation.

PREVENTION OF CANCER

The fact that only 5–10% of all cancer cases are due to genetic defects and that the remaining 90–95% are due to environment and lifestyle provides major opportunities for preventing cancer. Because tobacco, diet, infection, obesity, and other factors contribute approximately 25–30%, 30–35%, 15–20%, 10–20%, and 10–15%, respectively, to the incidence of all cancer deaths in the USA, it is clear how we can prevent cancer.

Almost 90% of patients diagnosed with lung cancer are cigarette smokers; and cigarette smoking combined with alcohol intake can synergistically contribute to tumorigenesis. Similarly, smokeless tobacco is responsible for 400,000 cases (4% of all cancers) of oral cancer worldwide. Thus avoidance of tobacco products and minimization of alcohol consumption would likely have a major effect on cancer incidence. Infection by various bacteria and viruses is another very prominent cause of various cancers. Vaccines for cervical cancer and HCC should help prevent some of these cancers, and a cleaner environment and modified lifestyle behavior would be even more helpful in preventing infection caused cancers.

Diet, obesity, and metabolic syndrome are very much linked to various cancers and may account for as much as 30–35% of cancer deaths, indicating that a reasonably good fraction of cancer deaths can be prevented by modifying the diet. Extensive research has revealed that a diet consisting of fruits, vegetables, spices, and grains has the potential to prevent cancer. The specific substances in these dietary foods that are responsible for preventing cancer and the mechanisms by which they achieve this have also been examined extensively. Various phytochemicals have been identified in fruits, vegetables, spices, and grains that exhibit chemopreventive potential, and numerous studies have shown that a proper diet can help protect against cancer (46, 67–69).

The protective role of fruits and vegetables against cancers that occur in various anatomical sites is now well supported (46,69). In 1966, Wattenberg (70) proposed for the first time that the regular consumption of certain constituents in fruits and vegetables might provide protection from cancer. Doll and Peto (21) showed that 75–80% of cancer cases diagnosed in the USA in 1981 might have been prevented by lifestyle changes.

According to a 1997 estimate, approximately 30–40%of cancer cases worldwide were preventable by feasible dietary means http://www.dietandcancerreportorg/?p=ER). Several studies have addressed the cancer chemopreventive effects of the active components derived from fruits and vegetables. More than 25,000 different phytochemicals have been identified that may have potential against various cancers. These phytochemicals have advantages because they are safe and usually target multiple cell-signaling pathways (71). Major chemopreventive compounds identified from fruits and vegetables include carotenoids, vitamins, resveratrol, quercetin, silymarin, sulphoraphane and indole-3-carbinol.

What is chemoprevention and how does it work?

Chemoprevention is the attempt to use natural and synthetic compounds to intervene in the early stages of cancer, before invasive disease begins. This strategy is involved in the process of carcinogenesis — the transformation of a normal cell into a cancer cell. Currently, the NCI has made chemoprevention research a top priority; more than 400 potential agents are currently under investigation. Chemopreventive agents can act in two ways: they can prevent or stop genetic mutations that lead to cancer, and they can prevent or stop processes that lead to excessive replication of damaged cells. Chemoprevention should not be confused with chemotherapy.

Chemotherapy’s aim is to kill cells, particularly cancer cells, in the hope of preventing further cancer progression. Chemoprevention, on the other hand, involves administering nontoxic agents to otherwise healthy individuals who may be at increased risk for cancer.Chemoprevention research is necessarily linked to diet and cancer research and represents a logical research progression.

Dietary epidemiologic studies have provided initial leads for the identification of numerous naturally occurring candidate chemopreventive agents, and laboratory studies have identified many potential agents that suppress carcinogenesis in animal models. Promising chemopreventive agents being investigated include micronutrients (eg, vitamins A, C, and E, beta-carotene, molybdenum, calcium), phytochemicals (eg, indoles, polyphenols, isothiocyanates, flavonoids, monoterpenes, organosulfides), and synthetics (eg, vitamin A derivatives, piroxicam, tamoxifen, 2-difluoromethylornithine [DFMO], and oltipraz).

Broadly defined on the basis of their mechanisms of action, chemopreventive agents can be grouped into two general classes: blocking agents and suppressing agents. Blocking agents (eg, flavonoids, oltipraz, indoles, isothiocyanates) prevent carcinogenic compounds from reaching or reacting with critical target sites by preventing the metabolic activation of carcinogens or tumor promoters by enhancing detoxification systems and by trapping reactive carcinogens.

Suppressing agents (eg, vitamin D and related compounds, nonsteroidal anti-inflammatory drugs [NSAIDs], vitamin A and retinoids, DFMO, monoterpenes, calcium) prevent the evolution of the neoplastic process in cells that would otherwise become malignant. Mechanisms of action for suppressing agents are not well understood.

Some produce differentiation, some counteract the consequences of genotoxic events such as oncogene activation, some inhibit cell proliferation, and some have undefined mechanisms. Certain chemopreventive agents may exhibit several different mechanisms of action simultaneously. The first FDA approved chemopreventive agent was tamoxifen, for reducing the risk of breast cancer.

This agent was found to reduce the breast cancer incidence by 50% in women at high risk..With tamoxifen, there is an increased risk of serious side effects such as uterine cancer, blood clots, ocular disturbances, hypercalcemia, and stroke. The second chemopreventive agent to reach to clinic was finasteride, for prostate cancer, which was found to reduce incidence by 25% in men at high risk. The recognized side effects of this agent include erectile dysfunction, lowered sexual desire, impotence and gynecomastia. Celecoxib, a COX-2 inhibitor is another approved agent for prevention of familial adenomatous polyposis (FAP).

However, the chemopreventive benefit of celecoxib is at the cost of its serious cardiovascular harm. The serious side effects of the FDA approved chemopreventive drugs is an issue of particular concern when considering long-term administration of a drug to healthy people who may or may not develop cancer. This clearly indicates the need for agents, which are safe and efficacious in preventing cancer. Diet derived natural products will be potential candidates for this purpose.

Relationship between Green Tea and Cancer

Multiple studies have demonstrated the effectiveness of green tea in reducing cancer risk. According to one such study, one cup of green tea each day was able to reduce ovarian cancer risk by
24 percent. More than one cup provided even more dramatic results. Two cups per day reduced the risk by 46%, and those women who drank green tea for over 30 years saw the rate of ovarian cancer drop a whopping 75%. Another study analyzed consumption among 40,000 Japanese subjects, taking gender, age, lifestyle and health into consideration. Dr. Toru Naganuma of Tohoku University concluded drinking green tea may have a favorable prevention effect for “particular cancers.”

Those who drank five or more cups were analyzed against those who drank less than a single cup of green tea daily. The study subjects’ health was also analyzed “in context of alcohol, soybean and fish consumption.” What was found is that five cups of green tea each day could reduce the risk of lymph cancers by up to 48%, and blood cancers by 42%. Of course this isn’t the only research shedding light on the relationship between green tea and cancer. Other findings also show how green tea can fight cancer cell growth by significantly reducing the number of lymphocytes.

Cancer Fighting Foods

Could it be that cancer rates are so rampant because people are simply not eating the right foods? While there are many factors that play into the development of cancer, diet and smoking habits make up nearly 60 percent of cancer cases. The good news is that with dietary and lifestyle changes, cancer rates can drop dramatically. One of the easiest ways to protect yourself against cancer is to consume many cancer fighting foods – here are 4 of them you should never forget about.

1. Turmeric (Curcumin)

Among the most currently researched of cancer fighting foods, turmeric has repeatedly been shown to be an effective cancer-fighter and even block cancer growth. Previously found to reduce tumors by an astounding 81%, the naturally occurring compound found in turmeric, curcumin, exhibits numerous anti-cancer properties. Researchers at UCLA found that curcumin is the component harnessing the ability to actually block cancer growth. Not surprisingly, the cancer-fighting ability that turmeric possesses makes up only a single facet of the many benefits of turmeric.

2. Papaya Leaf Extract

A study conducted by University of Florida researchers Dr.Nam Dang and colleagues in Japan has documented papaya’s powerful anticancer properties and impact against numerous lab-grown tumors – and without the negative consequences of chemotherapy. The researchers used papaya leaf extract for the study conduction, with the anticancer effects being even stronger with a larger dose of the extract.

What’s more, the extract can be taken for a long time without nasty side-effects. Another study also shows how papaya leaf extract is able to fight various cancers including cervix, breast, liver, lung, and pancreatic while aiding the cardiovascular and gastrointestinal systems.

3. Ginger

Adding another to the list of cancer fighting foods, ginger, a cousin spice of super anti-cancer substance turmeric, is known for its ability to shrink tumors. The subject of one study based out of Georgia State University, whole ginger extract was revealed to shrink prostate tumor size by 56% in mice. The anti-cancer properties were observed in addition to ginger’s role in reducing inflammation as well as being a rich source of lifeenhancing antioxidants. You definitely won’t want to disregard the health benefits of ginger.

4. Garlic

For centuries, the benefits of garlic have been experienced by many cultures for the treatment and prevention of disease; garlic’s status as one of the cancer fighting foods is perhaps one of the most notorious. Scientists believe that the anti-cancer properties may be due to the production of something known as hydrogen sulfide. Also known to protect the heart, researchers at Albert Einstein College of Medicine found that damage to the heart muscle as a result of heart attack is halted by directly injecting hydrogen sulfide into mice.

Researchers believe that the production of hydrogen sulfide is responsible for garlic’s ability to prevent various cancers including, prostate, breast, and colon cancer.

5. Mushrooms – a Functional Food and a potent natural based Chemopreventive Agents

Scientific evidence supports the view that diet controls and modulates many functions of the human body and, accordingly, participates in the maintenance of the state of good health or homeostasis. Arising from this awareness of the relationship between diet and disease has evolved the concept of functional foods and the development of functional food science. Foods as medicine underpin the paradigm of functional foods.

Mushrooms have long been valued as highly flavoursome and nutritional foods by many societies. In the Orient, there has long been the recognition that certain edible and nonedible mushrooms can have profound health benefits. When used as tonics the medicinal mushrooms are consumed whole or preferably as concentrated extracts and act as dietary supplements.

A limited number of highly purified compounds derived from certain medicinal mushrooms are now being used in the Orient and the US as pharmaceutical grade products in medicine – especially, but not exclusively, for cancer treatment.

The practice of using fungi, especially mushrooms, in Chinese Traditional Medicine (TCM), dates back into antiquity and has been recorded in ancient Chinese manuscripts. Increased scientific and medical research in recent decades, especially in Japan, Korea and China and more recently US, is confirming efficacy and identifying the bioactive molecules. The main active ingredients found in mushrooms are polysaccharides and terpenoids.

Together they exhibit a verity of medicinal and chemopreventive functions:

  • Mushrooms as Antioxidants
  • Mushrooms are Probiotic – they help our body strengthen itself and fight off illness by maintaining physiological homeostasis – restoring our bodies balance & natural resistance to disease.
  • Mushrooms have been used to treat a verity of liver disorders, including hepatitis.
  • Mushrooms as Immunoregulators. They contain Host Defense Potentiators (HDP) compounds which can have immune system enhancement properties.
  • Several different polysaccharides anti tumor agents have been developed from the fruiting body, mycelia, and culture medium of various medicinal mushrooms.
  • They are currently used as adjuncts to cancer treatments in Japan, Russia, China, and the U.S.A.

The main advantage of using mushroom products with respect to safety (when compared to herbal preparations) is:

  • Medicinal mushrooms that are cultivated commercially (not gathered from the wild). These guarantees proper identification and relatively pure, unadulterated products.
  • Mushrooms are easily propagated vegetatively and, thus, kept to one clone. The mycelium can be stored for a long time and the genetic and biochemical consistency may be checked over time.
  • The ability to grow most medicinal mushrooms as mycelium in fomenters under controlled conditions with consequent improved product purity.

Supplementary Note:

Mushrooms as anti-cancer therapeutics

Mushrooms have been regarded as gourmet cuisine across the globe since antiquity for their unique taste and subtle flavour. Recently, it has been discovered that many mushroom species are miniature pharmaceutical factories producing hundreds of novel constituents with miraculous biological properties.

They have a long history of use in Oriental medicine, but their legendary effects in promotion of good health and vitality are being supported by contemporary studies only. Of late, mushrooms have emerged as wonderful source of nutraceuticals, antioxidants, anticancer, prebiotic, immunomodulating, anti-inflammatory, cardiovascular, antimicrobial, and anti-diabetic (Barros et al. 2007; Sarikurkcu et al. 2008; Wang et al. 2004; Kim et al. 2007; Synytsya et al. 2009). The ongoing research projects are aimed to promote mushrooms as new generation ‘‘biotherapeutics’’.

Numerous clinical trials have been conducted to assess the benefits of using commercial preparations containing medicinal mushroom extracts in cancer therapy. Their potential uses individually and as adjuncts to cancer therapy have emerged. Mushrooms are known to complement chemotherapy and radiation therapy by countering the side-effects of cancer, such as nausea, bone marrow suppression, anemia, and lowered resistance.

Recently, a number of bioactive molecules, including anti-tumor agents, have been identified from various mushrooms. The bioactive compounds of mushrooms include polysaccharides, proteins, fats, ash, glycosides, alkaloids, volatile oils, tocopherols, phenolics, flavonoids, carotenoids, folates, ascorbic acid enzymes, and organic acids. The active components in mushrooms responsible for conferring anti-cancer potential are lentinan, krestin, hispolon, lectin, calcaelin, illudin S, psilocybin, Hericium polysaccharide A and B (HPA and HPB), ganoderic acid, schizophyllan, laccase, etc.

Polysaccharides are the best known and most potent mushroom-derived substances with anti-tumor and immunomodulating properties. The polysaccharide, b-glucan is the most versatile metabolite due to its broad spectrum biological activity. These bglucans consist of a backbone of glucose residues linked by b-(1 ? 3)-glycosidic bonds, often with attached side-chain glucose residues joined by b-(1 ? 6) linkages (Chen and Seviour 2007).

Their mechanisms of action involve their being recognized as non-self molecules, so the immune system is stimulated by their presence. Hispolon, an active polyphenol compound, is known to possess potent anti-neoplastic properties and potentiate the cytotoxicity of chemotherapeutic agents. The scientific investigations to back the claims have gained momentum in recent years. Findings suggest that some mushrooms in combination with commercial anti-cancer drugs work in synergy as an effective tool for treating drug-resistant cancers.

Antrodia Camphorata:

A Rare Fungus A potent chemopreventive agent Antrodia camphorata also called “the king of LingZhi” is a rare fungus found growing naturally only in Taiwan, on the inner cavity of the endangered species of the tree trunk of the plant Camphorata Kanehirai. Antrodia camphorata is a unique mushroom of Taiwan, which has been used as a traditional medicine for protection of diverse health-related conditions.

The list of bioactivities of crude extracts is huge, ranging from anti-cancer to vasorelaxation and others. Over 78 compounds consisting of terpenoids, benzenoids, lignans, benzoquinone derivatives, succinic and maleic derivatives, in addition to polysaccharides have been identified. Many of these compounds were evaluated for biological activity.

The bitter components of A. camphorata are Triterpenoids and have known pharmacological activities. Triterpenes are considered to be potential anti-cancer agents due to activity against growing tumors; they have direct cytotoxicity against tumor cells rather than to normal cells. To date it is concluded that A. camphorata can be considered as an efficient alternative phytotherapeutic agent or a synergizer in the treatment of cancer and other immunerelated diseases.

 

Reference: Review of Pharmacological Effects of Antrodia camphorata and its Bioactive Compounds; eCAM 2009 Special Supplementary Note: Common Chinese Medicine that have Anticancer Effects Chinese medicine is a unique medical system, have been used in main stream medical health care in China for years of thousands and have been accepted by many countries as complemental and alternative medicine. As one of the major traditional medicines and Ethno medicines in the world, following represent some common Chinese medicines that currently found to have anti-cancer effects:

Rhizoma coptidis (Huanglian 黃連 in Chinese)

Coptis Rhizome (CR) is the dried rhizome of Coptis chinensis Franch (Ranunculaceae). Its Chinese name is huanglian, Berberine is the main component and is credited as criteria for quality control of CR in China Pharmacopeia (Edition 2005). Recently, the most attractive pharmacological effect of CR and berberine is its anticancer activities (Tang et al., 2009). CR and berberine were used for prevention and treatment of human cancers, such as nasopharyngeal carcinoma (NPC), cholangecarsinoma with complication of liver cancer, and phase I study of CR (Chinese Herb) in patients with advanced solid tumors (Tian et al., 2000; Feng et al., 2008; http://cancer.gov/clinicaltrials/MSKCC-00061). Berberine is the principal active compound of anticancer effect in CR (Hara et al., 2005).

There are many reports showing that berberine could inhibit proliferation of cancer cells in gastric cancer, leukemia, melanoma, liver cancer, colorectal cancer, pancreas cancer, oral cancer, breast cancer, cervical cancer, lung cancer, NPC and prostate cancer cell line models and may have potential chemotherapeutic properties against human cancers (Lin et al., 2006; Jantova et al., 2003; Serafim et al., 2008; Piyanuch et al., 2007; Katiyar et al., 2009; Lin et al., 2004; Lee et al., 2006; Liu et al., 2005; Kim et al., 2004). Radix stephaniae tetrandrae (Han Fangji 漢防己 in Chinese) Radix stephaniae tetrandrae is the dried root of Stephania tetrandra S. Moore (Menispermaceae). With its Chinese name as Han Fangji.

A recent report that a Stephania tetrandra-containing Chinese Herb Formula, SENL, could reduce the expression of mutildrug resistanceassociated protein and increase the intracellular accumulation of chemotherapeutic agent, Adriamycin, in human lung cancer cell line SW1573/2R120 (Xu et al., 2010), indicating Stephania tetrandra could be used as a complementary agent in chemotherapy to enhancing cancer cell sensitivity to chemotherapeutic agents.

In contrast, as the major compound isolated from Stephania tetrandra, tetrandrine is extensively reported for its anti-tumor activity in various human cancers. (Chen et al., 2008). Tetrandrine was also reported to be capable of inducing cell apoptosis in various kinds of human cancers, including lung carcinoma (Lee, et al., 2002), leukemia (Jang et al., 2004), hepatoma (Ng et al., 2006), nasopharyngeal carcinoma (Sun et al., 2006) and colon cancer (Chen et al., 2008). Tetrandrine selectively inhibits the proliferation of Human lung carcinoma cellA549 (Cho et al., 2009). These studies indicate the multiple targets of tetrandrine in treating human cancers. Radix scutellariae (Huangqin黃苓 in Chinese) Radix scutellariae with the Chinese name of Huangqin, is the root of Scutellaria baicalensis Georgi (Labiatae). Modern studies denoted that Radix scutellaria has anti-cancer effect in various kinds of cancer cell lines including breast cancer cell (Zhou et al., 2009; Wang et al., 2010), lung cancer (Gao et al., 2010), leukemia (Kumagai et al., 2007), prostate cancer (Miocinovic et al., 2005) and so on.

Radix Ginseng (Renshen 人参 in Chinese)

Radix Ginseng, the dried root of Panax ginseng C.A. Meyer (Araliaceae), has been widely used as a tonic agent in traditional Chinese medicine for improvement in physical and mental capacities.
There is an increasing interest in radix ginseng regarding the human cancers. It is believed that the lifeprolonging effect of radix ginseng may be because of the protective effect against various cancers such as prostate cancer, ovarian cancer and lung adenocarcinoma [Kim et al., 2004; Liu et al., 2000; Nakata et al., 1989]. Ginsenosides are the major anti tumor constituents in radix ginseng.

Radix notoginseng (Sanqi/Tienchi 三七 in Chinese)

Radix notoginseng is the dried root of Panax notogiseng (Burk.) F. H. Chen (Araliaceae). Recently, several studies have demonstrated the inhibitory effects of Radix Notoginseng extract against a variety of human cancers, such as skin tumours, cervical cancer, prostate cancer, gastric cancer, colorectal cancer, sarcoma and breast cancer [Ng, 2006]. Laboratory studies on colorectal cancer suggested that Radix Notoginseng could be used alone or as adjuncts to existing chemotherapy to improve the outcomes of the chemotherapeutic treatment and reduce the adverse effects of chemotherapy [Wang et al., 2007; Wang et al., 2009; Sadeghi and Yazdanparast, 2005; Zhang et al., 2007].

Radix Salvia miltiorrhizae (Red Sage Root, Danshen 丹参 in Chinese)

Danshen is the root and rhizome of Salvia miltiorrhiza Bge. (Labiatae), The aqueous extract of Danshen can inhibit the proliferation of HepG2 cells (Jiang et al.,2005). Salvinal, a compound identified from aqueous extract, inhibiting tubulin polymerization, arresting the cell cycle at mitosis, and inducing apoptosis in multidrug sensitive and -resistant human tumor cells (Chang et al., 2004).

Another hydrophilic component Salvianolic acid B inhibits growth of head and neck squamous cell carcinoma in vitro and in vivo via inhibiting cyclooxygenase-2 expression (Hao et al., 2009). The chishen extract (CSE) from the water-soluble compounds of Salvia miltiorrhiza and Paeoniae radix shows anticancer effects (Hu et al., 2007). Tanshinone IIA can induce apoptosis in HL60, CNE1, SPC-A-1, NB4, K562 and HepG2 cell lines, (Yoon et al., 1999; Yuan et al., 2003; Lee et al., 2008; Zhou et al., 2008 ).

Tanshinone IIA can inhibite the proliferation of non-small cell lung cancer A549 cells (Chiu and Su 2010). Tanshinone I induces apoptosis, suppresses growth and invasion in MCF-7 and MDA-MB-231 breast cancer cell line, Tanshinone I also exerts anticancer effect in highly invasive human lung adenocarcinoma cell line, CL1-5 and CL1-5-bearing severe combined immunodeficient mice (Lee et al., 2008). Extract from: Molecular and Cellular Mechanism Studies on Anticancer Effects of Chinese Medicine; Biomedical Engineering, Trends, Research and Technologies; ISBN 978-953-307-514-3