The anti-carcinogenic benefits of selected foods have been discussed below along with the available scientific evidences:
1. Saffron (Crocus Sativus):
One of the most promising strategies for cancer prevention today is chemo- prevention using readily available natural substances from vegetables, fruits, herbs and spices. Among the spices, saffron (Crocus sativus, L) a member of the large family Iridaceae, in the in vitro colony-forming test system, displayed a dose-dependent inhibitory effect only against human malignant cells.
All isolated carotenoid ingredients of saffron demonstrated cytotoxic activity against in vitro tumor cells. Saffron crocin derivatives possessed a stronger inhibitory effect on tumor cell colony formation. Overall, these results suggest that saffron itself, as well as its carotenoid components, might be used as potential cancer chemo-preventive agents.
Significant reduction in papilloma formation was found with saffron application in the pre-initiation and post-initiation periods, and particularly when the agent was given both pre- and post-initiation. The inhibition appeared to be at least partly due on modulatory effects of saffron on some phase II detoxifying enzymes like glutathione-S-transferase (GST) and glutathione peroxidase (GPx), as well as catalase (CAT) and superoxide dismutase (SOD).
Das et al (2010) also found saffron to inhibit DMBA-induced skin carcinoma in mice when treated early which according to them may be due at least in part, to the induction of cellular defense systems. Amin et al (2011) provided evidence that saffron exerts a significant chemo- preventive effect against liver cancer through inhibition of cell proliferation and induction of apoptosis and also protects rat liver from cancer via modulating oxidative damage and suppressing inflammatory response.
Doses inducing 50 per cent cell growth inhibition (LD50) on HeLa cells were 2.3 mg/ml for an ethanolic extract of saffron dry stigmas, 3 mM for crocin, 0.8 mM for safranal and 3 mM for picrocrocin. Crocetin did not show cytotoxic effect. Cells treated with crocin exhibited wide cytoplasmic vacuole-like areas, reduced cytoplasm, cell shrinkage and pyknotic nuclei, suggesting apoptosis induction. Considering its water-solubility and high inhibitory growth effect, crocin is the more promising saffron compound to be assayed as a cancer therapeutic agent.
Crocin isolated from Kashmiri saffron decreased cell viability in Dalton’s lymphoma cells, in a concentration and time-dependent manner. Significant increase in the lifespan of Dalton’s lymphoma bearing animals was noted by 37 per cent and 44 per cent, in vitro and in vivo respectively.
Animals given treatment with crocin prior to induction of cancer showed 58 per cent increase in lifespan and 95.6 per cent reduction of solid tumor on the 31st day after tumor inoculation. Crocin also showed significant impact on hematological parameters, like the hemoglobin count and numbers of lymphocytes thus proving that crocin from Crocus sativus has significant anti-tumor activity.
2. Cumin Seeds (Cuminum Cyminum):
Medicinal plants are considered as potential sources of new chemotherapeutic drugs because of their diverse phytochemicals and little or no toxic effect. Among the nine plant products tested, cumin seeds significantly decreased the incidence of both B[a]P-induced neoplasia and 3’MeDAB-induced hepatomas.
They observed that cumin seed significantly decreased the incidence of both benzo [a] pyrene P-induced neoplasia and 3′-methyl-4-dimethyl- aminoazobenzene -induced hepatomas in mice and suggested that it could be attributed to its ability to modulate carcinogen metabolism and thus may prove to be valuable anti-carcinogenic agent.
Cumin seeds increased the carcinogen-detoxifying enzyme, glutathione-S- transferase activity by more than 78 per cent in the stomach, liver and oesophagus, high enough to be considered as protective agents against carcinogenesis. Also it significantly suppressed (in vivo) the chromosome aberrations (CA) caused by benzo (a) pyrene in mouse bone marrow cells to be considered as protective agents against carcinogenesis. Glutathione levels were also significantly elevated in all the three tissues thus proving its anti-cancer benefit.
Colon cancer is the second most common cancer among men and women worldwide. Cumin and black pepper may protect the colon by decreasing the activity of beta-glucuronidase and mucinase. Histo-pathological studies also showed lesser infiltration into the submucosa, fewer papillae and lesser changes in the cytoplasm of the cells in the colon in cumin and black pepper treated animals. Nalini et al. (2006) confirmed that cumin suppresses colon carcinogenesis in the presence of a colon-specific carcinogen, 1, 2-dimethyl hydrazine (DMH) and significantly lowers the number of tumors in the colon.
According to Gagandeep et al. (2003) reduction in tumor burden and significant elevation of the specific activities of superoxide dismutase (p < 0.01) and catalase (p< 0.05) and other related observations strongly suggest the chemo-preventive potentials of cumin seed and its ability to modulate carcinogen metabolism.
3. Kalaumji or Kaljeera (Nigella Sativum):
Constituents of the Nigella sativa seed are reported to possess potent anti-oxidant effects. Treatment with anti-cancer drugs such as cyclo-phosphamide (CTX) is associated with significant toxicity due to over-production of reactive oxygen species, resulting in increased levels of oxidative stress. Alenzi et al. (2010) found that the administration of NSO or TQ can lower CTX-induced toxicity as shown by an up- regulation of anti-oxidant mechanisms, indicating a potential clinical application for these agents to minimize the toxic effects of treatment with anti-cancer drugs.
Salim and Fukushima (2003) demonstrated that the volatile oil of N. sativa has the ability to inhibit colon carcinogenesis of rats in the post-initiation stage, with no evident adverse side effects, and that the inhibition may be associated, in part, with suppression of cell proliferation in the colonic mucosa.
4. Black Pepper (Piper Nigrum) and Hot Pepper:
Black pepper (Piper nigrum) and hot pepper (Capsicum spp.) are widely used in traditional medicines. Hot Capsicum spp. extracts and its active principles, capsaicinoids, have been linked with anti-cancer and anti-inflammatory activities. The alkyl amides and piperine from black pepper suppressed TNF-induced NF-kappa B activation. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is an ingredient of chilli peppers with inhibitory effects against cancer cells of different origin.
Capsaicin induces cellular apoptosis through a caspase-independent pathway in MCF-7 cells, and that reactive oxygen species and intracellular calcium ion fluctuation has a minimal role in the process. The human cancer cell proliferation inhibitory activities of piperine and alklyl amides in capsicum and black pepper were dose dependant suggesting that black pepper and its constituents like hot pepper, exhibit anti-inflammatory, antioxidant and anti-cancer activities.
According to Thoennissen et al. (2010) capsaicin is a novel modulator of the epidermal growth factor receptor (EGFR/HER-2) pathway in both ER positive and negative breast cancer cells with a potential role in the treatment and prevention of human breast cancer. The anti-inflammatory potential of capsaicin is attributed to its inhibitory effect on inducible COX-2 mRNA expression.
Cytochrome P4502E1 mediates the activation of xenobiotic such as vinyl carbamate and dimethyl nitrosamine to their toxic metabolites. This metabolic activation of xenobiotic by Cytochrome P4502E1 has been shown to be inhibited by capsaicin. Capsaicin also generates reactive oxygen species in cells with resultant induction of apoptosis and cell cycle arrest, which is beneficial for cancer chemo-prevention.
The inhibitory effects of capsaicin on cancer development in multiple organs, such as stomach, lung, and liver have been extensively documented. These inhibitory effects of capsaicin on promoter through the inactivation of two defined eukaryotic transcription factors – Nuclear Factor-kappaB (NF-kB), and activator protein 1 (AP-1) have been reported. Therefore, capsaicin suppresses TPA-stimulated activation of NF-kB through inhibition of IkBa degradation and blockade of the subsequent nuclear translocation of p65 in human pro-myelocytic leukemia HL-60 cells.
Majdalawieh and Carr (2010) confirmed that black pepper and cardamom exert immuno-modulatory roles and anti-tumor activities, and hence they manifest themselves as natural agents that can promote the maintenance of a healthy immune system. It is possible that black pepper and cardamom constituents can be used as potential therapeutic tools to regulate inflammatory responses and prevent/attenuate carcinogenesis.
5. Tea:
Tea is one of the most widely consumed beverages, second only to water. Many experimental researches in laboratory animals demonstrated that tea components had an inhibitory effect on carcinogenesis at a number of organ sites. The anti- carcinogenic effects of tea have been attributed to the modulation of mitotic signal transduction by the polyphenol fraction of tea.
Tea consumption has also been shown to afford protection against chemical carcinogen-induced stomach, lung, esophagus, duodenum, pancreas, liver, breast, and colon carcinogenesis in specific bioassay models. Several epicatechin derivatives (polyphenols) present in green tea have been shown to possess anti-carcinogenic activity; the most active is (-)-epigallocatechin-3-gallate (EGCG), which is also the major constituent of Green Tea Polyphenols (GTP).
Several theories have been put forward, including inhibition of UV and tumor promoter-induced ornithine decarboxylase, cyclo-oxygenase, and lipoxygenase activities, antioxidant and free radical scavenging activity; enhancement of antioxidant (glutathione peroxidase, catalase, and quinone reductase) and phase II (glutathione-S-transferase) enzyme activities; inhibition of lipid peroxidation, and anti-inflammatory activity. These properties of tea polyphenols make them effective chemo-preventive agents against the initiation, promotion, and progression stages of multistage carcinogenesis.
A growing number of studies document EGCG-mediated induction of apoptotic pathways and inhibition of pro-survival factors when combined with chemotherapy or radiation. Ferrario et ah (2011) demonstrated the efficacy of EGCG in modulating photofrin (PH)-mediated photodynamic therapy responses by increasing tumor apoptosis and decreasing expression of pro-survival and angiogenic molecules within the tumor micro-environment.
6. Cloves (Syzygium Aromaticum):
Banerjee and Das (2005) have shown that oral administration of aqueous infusions of clove at a dose of 100 microl/mouse/day not delayed the formation of papilloma but also reduced the incidence of papilloma as well as the cumulative number papillomas per papilloma bearing mouse. Aqueous infusion of clove effectively reduced Incidence of hyperplasia, dysplasia and carcinoma in mice. Significant reduction in the number of proliferating cells and an increased number of apoptotic cells was also noted in these benzo (a) pyrene induced lung lesions following clove treatment.
Western blotting analysis revealed that clove infusion up-regulates the expression of pro-apoptotic proteins p53 and Bax, and down-regulates the expression of anti-apoptotic protein Bcl-2 in the pre-cancerous stages. Expression of caspase 3 and its activation by clove infusion were evident from a very early stage of carcinogenesis (eighth week). Clove infusion was also found to down-regulate the expression of some growth-promoting proteins, viz, COX-2, cMyc, Hras.
The water, ethanol and oil extracts of cloves tested against HeLa (cervical cancer), MCF-7 (ER + ve) and MDA-MB-231 (ER – ve) (breast cancer), DU-145 (prostate cancer) and TE-13 (esophageal cancer) cell lines in vitro, showed different patterns of cell growth inhibition activity, with the oil extract having maximal cyto-toxic activity.
Maximum cell death and apoptotic cell demise occurred in TE-13 cells within 24 hours by clove oil at 300 µl/ml with 80 per cent cell death whereas DU-145 cells showed minimal cell death. At the same time, no significant cyto-toxicity was found in human PBMC’s at the same dose.
7. Oils, Butter and Ghee:
Dietary fat intake is also associated with incidence of cancer. A strong positive correlation between fat intake and age adjusted incidence and mortality due to breast cancer is evident among women. Vegetable oils have been reported to enhance 7,12-dimethylbenz (a) anthracene (DMBA) induced mammary adenocarcinomas more than butter and some other saturated fats in rodents. High intake of unsaturated fatty acids enhances tumour development due to increased synthesis of prostaglandins. Conjugated linoleic acid (CLA) is considered anti-carcinogenic.
The CLA content of cow and buffalo ghee prepared by using (a) desi method, (b) direct cream method without starter, (c) direct cream method with starter, was analyzed. Ghee prepared with desi method was found to contain highest CLA levels and it was higher in buffalo than cow ghee. Ghee contains conjugated linoleic acid (CLA) which has been shown unequivocally to inhibit mammary carcinogenesis.
PPARγ are the key components in regulation of growth and progression of mammary cancer. The expression of PPARγ was significantly more on cow ghee than on soybean oil. In the genesis of breast cancer, evidence suggests that induction of COX-2 and down regulation of PPARγ can be the key components.
Histological analysis showed rapid progression of cancer in soybean oil fed rats than rats fed cow ghee. The expression of cyclooxygenase-2(COX-2) was significantly less in cow ghee fed rats compared to those on soybean oil and was associated with decreased tumour incidence. Over expression of COX-2 in rats induces mammary tumours.
Rani and Kansal (2011) investigated the effect of feeding cow ghee versus soybean oil on DMBA induced mammary cancer and expression of cyclooxygenase-2 and perisome proliferators activated receptor-γ (PPARγ) in mammary gland in 21 day old female rats. Animals fed soybean oil had higher tumour incidence (65.4 per cent), tumour weight (6.18g) and tumour volume (6285mm3) compared to those fed cow ghee (26 per cent, 1.67g, 1925 mm3 respectively). However, further research is essential to understand the regulation of COX-2 and PPARγ apoptotic signaling, cell proliferation and prostaglandin synthesis in response to dietary fat.
Ghee has protective effects against side effects of radiation or chemotherapy. The common side effects of radiation or chemotherapy are loss of appetite, pain, nausea, vomiting, diarrhoea and mucositis which makes eating difficult. Loss of appetite is a cause of concern it results in undesirable weight loss, loss of muscle mass and decreased immunity.
Yashtimadhu (Glycyrrhiza glabra) Ghrita, a herbal preparation was administered to patients receiving chemotherapy for neck or head malignancies. Application of Yashtinadhu powder with honey and consumption of ghee was effective in prevention and treatment of oral mucositis post radiations.
Whey Protein Concentrate:
Animal experiments showed that the concentrates of whey proteins exhibit anti- carcinogenesis and anticancer activity by increasing glutathione (GSH) concentration in relevant tissues, and may have anti-tumor effect on low volume of tumor via stimulation of immunity through the GSH pathway.
8. Honey:
Honey was found to be a suitable alternative for wound healing, burns and various skin conditions, and to potentially have a role in cancer care. Bardy et al. (2008) opine that in the cancer setting, honey may be used for radiation-induced mucositis, radiotherapy-induced skin reactions, hand and foot skin reactions in chemotherapy patients and for oral cavity and external surgical wounds.
Honey applied topically to the oral mucosa of patients undergoing radiation therapy appears to provide a distinct benefit by limiting the severity of mucositis. Rashad et al. (2009) confirmed the prophylactic use of pure natural honey as effective in reducing mucositis resulting from radio-chemotherapy in patients with head and neck cancer. In the case of oral squamous cell carcinomas (OSCC) and human osteosarcoma (HOS) the treatment includes surgery and /or radiotherapy which often lead to reduced quality of life.
Ghashm et al. (2010) proved that Tualang honey has anti-proliferative effect on OSCC and HOS cell lines by inducing early apoptosis. Tomasin and Gomes-Marcondes (2011) also confirmed that honey can modulate tumour growth by reducing cell proliferation and increasing apoptosis susceptibility.
Honey may also cause cell death in the human renal cancer cell lines (ACHN), in which apoptosis plays an important role. Most of the drugs used in the cancer treatment are apoptotic inducers, hence apoptotic nature of honey is considered vital. Samarghandian et al. (2011) prepared cell cultures in Dulbecco’s modified Eagle’s medium with 10 per cent fetal bovine serum treated with different concentrations of honey for 3 consecutive days.
Cell viability was quantified by the 3-(4, 5- Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Apoptotic cells were determined using Annexin-V-fluorescein isothiocyanate (FITC) by flow cytometry. They found a decrease in the cell viability in the malignant cells with honey in a concentration and time-dependent manner.
Ehrlich ascites carcinoma is a spontaneous murine mammary adeno-carcinoma adapted to ascites form and carried in outbred mice by serial intra-peritoneal (i/p) passages. Jagannathan’s team (2010) showed that honey containing higher phenolic content significantly inhibited the growth of Ehrlich ascites carcinoma suggesting honey and eugenol (one of the phenolic constituents of honey) to be promising remedies in cancer chemo-prevention. Again, Jagannathan et al. (2011) demonstrated molecular mechanism of eugenol-induced apoptosis in human colon cancer cells and thus, reinforce eugenol as a potential chemo-preventive agent against colon cancer.
Jagannathan (2011) promulgates honey with common flavonoids like chrysin, genistein, biochanin, quercetin, kaempferol, and naringenin as potential components for reversing multi drug resistance (MDR). He foresees that honey, a novel chemo- sensitizer, can reduce the huge amount invested in developing new chemo-sensitizers to overcome the burden of chemo-resistance. Moreover, honey is readily available, affordable and well accepted by patients. Hence, it is useful for improving the quality of life in cancer patients undergoing radiation therapy.
Shoma et al. (2010) demonstrated a striking regression of the mean projected coetaneous surface area of lesions among breast cancer patients undergoing radiotherapy. A shorter duration of treatment and complete recovery after 12 weeks was observed among a group of patients who were treated with honey along with standard burn treatment and pentoxifylline (PTX). Moreover, the addition of honey was associated with marked relief of pain and rescue of proper motion. Thus it is proved that combination of PTX and honey is an ideal measure for treatment of radiation-induced burn following breast conservative surgery.
One of the major stumbling blocks for cancer chemotherapy is multidrug resistance (MDR) developed by cancer cells. Since ancient times, honey has been used successfully for the treatment of a broad spectrum of infections with no risk of resistance development. MDR in nosocomial pathogens is a continually evolving and alarming problem in health care units.
Majtan et al. (2011) proved that Honeydew honey with strong anti-bacterial activity could be used as a potential agent to eradicate multidrug resistant clinical isolates as Slovak Honeydew honey showed exceptional antibacterial activity against multi-drug resistant S. maltophilia isolates and was more efficient than Manuka honey.
Fauzi et al. (2011) showed that Tualang honey (TH) has significant anti-cancer activity against human breast and cervical cancer cells as there was an increase in lactate dehydrogenase leakage from the cell membranes indicating that TH is cytotoxic to all the cancer cells with effective concentrations of 2.4 – 2.8 per cent.
But when the effect of active Manuka honey was assessed on radiation-induced mucositis in 131 patients (diagnosed with head and neck cancer and undergoing radiotherapy), by Bardy et al. (2012) it was not found to improve mucositis. But both the honey and the syrup seemed to be associated with a reduction in bacterial infections. But, it was presumed by the authors that poor compliance after the onset of mucositis, may have affected the findings.
Honey may also cause cell death in the human renal cancer cell lines, in which apoptosis plays an important role. Most of the drugs used in the cancer treatment are apoptotic inducers, hence apoptotic nature of honey is considered vital. Samarghandian et al. (2011) found a decrease in the cell viability in the malignant cells with honey in a concentration and time-dependent manner.
Tomasin and Gomes-Marcondes (2011) verified the influence of Aloe vera and honey on tumour growth and in the apoptosis process by assessing tumour size, the cell proliferation rate (Ki67-LI) and Bax/Bcl-2 expression at 7,14 and 20 days after Walker 256 carcinoma implant in Wistar rats.
A decrease in relative weight (per cent) and Ki67-LI in tumours from the Aloe vera and honey group was observed as compared to those from the control group. The Bax/Bcl-2 ratio increased in tumours of the experimental group at all tested time points. These data suggest Aloe vera and honey can modulate tumor growth by reducing cell proliferation and increasing apoptosis susceptibility.