Cancer remains to be one of the leading causes of death in the United States and around the world. The advent of modern drug-targeted therapies has undeniably improved cancer patients’ cares. However, advanced metastasized cancer remains untreatable. Hence, continued searching for a safer and more effective chemoprevention and treatment is clearly needed for the improvement of the efficiency and to lower the treatment cost for cancer care. Cancer chemoprevention with natural phytochemical compounds is an emerging strategy to prevent, impede, delay, or cure cancer. This review summarizes the latest research in cancer chemoprevention and treatment using the bioactive components from natural plants. Relevant molecular mechanisms involved in the pharmacological effects of these phytochemicals are discussed. Pharmaceutical developmental challenges and opportunities in bringing the phytochemicals into the market are also explored. The authors wish to expand this research area not only for their scientific soundness, but also for their potential druggability.
There is scientific evidence that herbal remedies alone can cure or treat cancer. However, some plant extracts have been found to have anti-cancer effects and have been turned into chemotherapy drugs. These include vincristine from the periwinkle plant, and taxanes from the bark of the Pacific yew tree.
Natural plants have been used to prevent and to treat various diseases for thousands of years. The ancient Chinese emperor, the Red Emperor, or Shen Nung, compiled the first medicinal herbal literature, Pentsao in 2,800 BC . In dealing with diseases, prevention is considered a superior approach. As illustrated by the Huang-Di Nei-Jing, a manuscript believed being written by the ancient Chinese emperor, the Yellow Emperor, “The Saint treats those ill-to-be rather than those being ill, and cares for those in normality rather than those in chaoses. Drug a disease after it’s developed, or quench a chaos after it’s evident, is same as dig a well when in thirsty, or casting a sword in a battle — Is that somewhat late?”
There are excellent sources of bioactive components exerting their health beneficial effects, and very often, these sources are materials for gourmet food consumptions. Certain bioactive components from the plants have been confirmed for their anti-cancer activities. There is an estimate that approximately 50-60% of cancer patients in the United States utilize agents derived from different parts of plants or nutrients (complementary and alternative medicine), exclusively or concomitantly with traditional therapeutic regimen such as chemotherapy and/or radiation therapy . These include curcumin from tumeric, genistein from soybean, tea polyphenols from green tea, resveratrol from grapes, sulforaphane from broccoli, isothiocyanates from cruciferous vegetables, silymarin from milk thistle, diallyl sulfide from garlic, lycopene from tomato, rosmarinic acid from rosemary, apigenin from parsley, and gingerol from gingers, just to name a few.
Various review articles summarized natural phytochemicals and their anti-cancer effects. In recent years, some of these reviews touched the general overview for the bioactive aspect for phytochemical compounds , or specific compounds such as Vitamin E from plant oil ], boron-rich natural compound , hydroxytyrosol from virgin olive oil , resveratrol from grapes , phytoestrogens most notably from soybean , or EGCG from green tea polyphenols , while the others are more specific for certain cancers, e.g., colorectal cancer , breast cancer], head and neck cancer , pancreatic cancer [, prostate cancer , or protein targets and pathway mechanisms, such as Nrf2 [, COX-2 , PLK1 , angiogenesis . In this review, we will provide a comprehensive summary for the current status of the research and challenges in this area .
Medieval as it sounds, scientists are testing a recipe of wormwood and iron on breast cancer cells, and so far the results are encouraging. In a new study, researchers report that artemesinin–a derivative of the wormwood plant–kills iron-enriched breast cancer cells but doesn’t harm many healthy ones. Artemesinin’s destructive properties are triggered by higher than normal levels of iron in cancer cells.
Many experiments have found that artemesinin turns deadly in the presence of iron. In Asia and Africa, artemesinin tablets are widely and, in many cases, successfully used to treat malaria, because the parasite has a high iron concentration. Cancer cells can also be rich in iron, as they often soak up the mineral to facilitate cell division. The cells bring in extra iron with the help of transferrin receptors, special receiving points that funnel the mineral into the cell. Although normal cells also have transferrin receptors, cancerous ones can have many more.
To test artemesinin’s effect on breast cancer cells, bioengineers Henry Lai and Narendra Singh of the University of Washington, Seattle, enriched segregated normal breast cells and radiation-resistant cancerous ones with holotransferrin, a compound normally found in the body that carries iron to the cells. Then the team dosed the cells with artemesinin. As the pair reports in the 16 November issue of Life Sciences, almost all the cancer cells exposed to holotransferrin and artemesinin died within 16 hours. The compounds killed only a few of the normal cells. Lai believes that because a breast cancer cell contains five to 15 more receptors than normal, it absorbs iron more readily and hence is more susceptible to artemesinin’s attack.
Phytochemicals used as cancer chemopreventive and treatment agents
Apigenin from parsley
Apigenin is a flavone present in vegetables such as parsley, celery, chamomile , and Egyptian plant Moringa peregrina . It demonstrates cytotoxic activities against breast cancer cell lines (MCF 7), colon cell line (HCT 116), and its cytotoxic activity is comparable to that of doxorubicin.. Apigenin is also being considered as a mediator for chemoprevention in the cancerous process and induces a process of autophagia but may induce resistance against chemotherapy . It induces apoptosis in human colon cancer cells ], reduces azoxymethane (AOM) induced aberrant crypt foci (ACF) formation in male Sprague-Dawley rats, and increases apoptosis which may contribute to the colon cancer prevention ]. Apigenin affects leptin/leptin receptor pathway, and induces cell apoptosis in lung adenocarcinoma cell line . It also increases melanogenesis in B16 cells by activating the p38 MAPK pathway at least partially and suggests that apigenin or its derivatives may potentially be used for treating hypopigmentation disorders . Apigenin has been shown to be one of the beneficial compounds in various stages of carcinogenesis. In a recent review by Clere et al, the preventive and therapeutic effects of Apigenin and other flavonoids was summarized to facilitate the extrapolation from animal studies to human .
Curcumin from turmeric
Curcumin (diferuloylmethane) is the major components of popular Indian spice turmeric, Curcuma longa L., a member of the ginger family. Its anti-cancer effects have been studied for colon cancer, breast cancer, lung metastases, and brain tumor .
Curcumin’s anticancer effect is attributed to its ability to induce apoptosis in cancer cells without cytotoxic effects on healthy cells, which is very attractive to cancer research scientists. Curcumin interferes with NF-κB , which connects with inflammatory diseases including cancer . Curcumin was able to dissociate raptor from mTOR, inhibit mTOR complex I and might represent a new class of mTOR inhibitor . Ravindran et al suggested that curcumin modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-x, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21), death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK) . Curcumin inhibits p65 and cell invasion by downregulation of COX-2 and MMP-2 expression ; by suppression of gene expression of EGFR and modulation of Akt/mTOR signaling, and inhibition of cell growth . It has also been reported that curcumin suppresses p38 mitogen-activated protein kinase (MAPK) activation, reduces IL-1 beta and matrix metalloproteinase-3, and enhances IL-10 in the mucosa of children and adults with inflammatory bowel disease . Epstein and co-workers had a thorough review on in vitro, animal and clinical studies . In that review, curcumin is cited as non-toxic to human subjects at a high oral dose of up to 12 g/day, and it has anti-inflammatory, antioxidant and anti-cancer properties, however, under some circumstances, its effects can be contradictory as the first clinical trial failed to show benefit, which may be due to an unexpected lack of cognitive decline in placebo group . In our lab, curcumin was studied for modulating AP-1 in human colon HT-29 cancer cell line and was found increasing AP-1-luciferase activity dose-dependently from 1 to 25 μM, and the expression of endogenous cyclin D1 protein was well correlated with those of AP-1-luciferase assay . It inhibited NF-κB stimulator lipopolysaccharide (LPS)-induced inflammation, reduced LPS-induced IκB phosphorylation, and potently inhibited cell growth in MTS assay. Caspase-3 activity was also induced by curcumin . Among our other studies, Affymetrix mouse genome 430 array (45K) was used to analyze mouse liver and intestine mRNA after oral dose of curcumin at 1,000 mg/kg. Our results showed that 822 (664 induced and 158 suppressed) and 222 (154 induced and 68 suppressed) genes in the liver and small intestine, respectively, were curcumin-regulated Nrf2 dependent, which can be classified as ubiquitination and proteolysis, electron transport, detoxification, transport, apoptosis and cell cycle control, cell adhesion, kinase and phosphatase, and transcription factor . Another study from our lab found curcumin inhibited the phosphorylation of Akt, mTOR, and their downstream substrate in human prostate cancer PC-3 cells concentration- and time-dependently. And the inhibition of Akt/mTOR signaling by curcumin resulted from calyculin A-sensitive protein phosphatase-dependent dephosphorylation . We have also investigated combination of curcumin with sulforaphane , with PUFA [, with PEITC in inhibiting the growth of human PC-3 prostate xenografts in immunodeficient mice and in inhibiting EGFR signaling in human prostate cancer PC-3 cells and these studies demonstrated various levels of synergistric effects.
Crocetin from saffron
Saffron is a spice from the flower of the Saffron crocus and a food colorant present in the dry stigmas of the plant Crocus sativus L. . In a recent review article, saffron is listed as a potential agent for a novel anti-cancer drug against hepatocellular carcinoma . Saffron and its ethanolic extracts are also reported for the studies on human lung cancer , pancreatic cancer cell line , skin carcinoma , colorectal cancer cells , and breast cancer . Its applications and mechanism of actions are reviewed by Bathaie and Mousavi , and more recently, by Gutheil and Reed . Yet, it has been concluded that the exact mechanism of action is still not clear. In general, crocetin affects the growth of cancer cells by inhibiting nucleic acid synthesis, enhancing anti-oxidative system, inducing apoptosis and hindering growth factor signaling pathways . Nam’s study has shown that crocetin is effective for the inhibition of LPS-induced nitric oxide release, for the reduction of the produced TNF-α, IL-1β, and intracellular reactive oxygen species, for the activation of NF-κB, and blockage of the effect of LPS on hippocampal cell death . Although some studies beyond those mentioned above are successfully conducted, more thorough understanding of the mechanism on crocetin and its effects are needed.
Cyanidins from grapes
Cyanidin is an extract of pigment from red berries such as grapes, blackberry, cranberry, raspberry, or apples and plums, red cabbage and red onion. It possesses antioxidant and radical-scavenging effects which may reduce the risk of cancer. It is reported to inhibit cell proliferation, and iNOS and COX-2 gene expression in colon cancer cells . Another study shows that cyanidin-3-glucoside (C3G) attenuated the benzo[a]pyrene-7,8-diol-9,10-epoxide-induced activation of AP-1 and NF-κB and phosphorylation of MEK, MKK4, Akt, and MAPKs, blocked the activation of the Fyn kinase signaling pathway, which may contributed to its chemopreventive potential . C3G blocks ethanol-induced activation of the ErbB2/cSrc/FAK pathway in breast cancer cells and may prevent/reduce ethanol-induced breast cancer metastasis. Cyanidin-3-O-glucoside, cyanidin-3-O-rutinoside, and the ethanol extract of their source of freeze-dried black raspberries selectively caused significant growth inhibition and induction of apoptosis in a highly tumorigenic rat esophagus cell line (RE-149 DHD) but not in a weakly tumorigenic line (RE-149) . Cyanidin markedly inhibited UVB-induced COX-2 expression and PGE2 secretion in the epidermal skin cell line by suppressing NF-κB and AP-1 which are regulated by MAPK. In that study, MKK-4, MEK1 and Raf-1 are targets of cyanidin for the suppression of UVB-induced COX-2 expression . Cyanidin-3-galactoside and cyanidin-3-glucoside are found to be BCRP substrates, and cyanidin, cyanidin-3,5-diglucoside, and cyanidin-3-rutinoside are potential BCRP inhibitors but their effects on MDR1 were weak . This finding may be helpful for the further development of these compounds for clinical studies and may explain their pharmacokinetic performance in vivo.
Diindolylmethane (DIM) /Indole-3-carbinol (I3C) from Brassica vegetables
Indole-3-carbinol (I3C) is found in Brassica vegetables, such as broccoli, cauliflower, collard greens. Diindolylmethane (DIM) is a digestion derivative of indole-3-carbinol via condensation formed in the acidic environment of the stomach. Both are studied for their anticarcinogenic effects
I3C has been studied for cancer prevention and therapy for years for tobacco smoke carcinogen-induced lung adenocarcinoma in A/J mice and it was found that the lung cancer preventive effects are mediated via modulation of the receptor tyrosine kinase/PI3K/Akt signaling pathway, at least partially . I3C and DIM demonstrated exceptional anti-cancer effects against hormone responsive cancers like breast, prostate and ovarian cancers . In a recent study, it is concluded that DIM rather than I3C is the active agent in cell culture studies .
DIM showed anti-cancer properties and is currently in clinical trials for various forms of cancers. DIM transduces signaling via aryl hydrocarbon (Ah) receptor, NF-κB/Wnt/Akt/mTOR pathways, impinging on cell cycle arrest, modulated key CYP enzymes, altering angiogenesis, invasion, metastasis and epigenetic behavior of cancer cells . DIM, along with I3C were found to induce Nrf2-mediated phase II drug metabolizing (GSTm2, UGT1A1, and NQO1) and antioxidant (HO-1 and SOD1) genes and also shown synergism with isothiocyanates, such phenethyl isothiocyanate (PEITC) and sulforaphane (SFN) . Lubet et al found that I3C acts as AhR agonist in mammary cancers while DIM does not, and DIM is not analogous to I3C in exerting their anticarcinogenesis effects. DIM and I3C may act more effectively at earlier stage of prostate carcinogenesis and likely through a combination of effects on steroid hormones and/or xenobiotic metabolism pathway .
Epigallocatechin gallate from green tea
EGCG is the most abundant catechin compounds in green tea. Increasing evidences show that EGCG can be beneficial in treating brain, prostate , cervical , and bladder cancers. Yang et al reviewed tea and cancer prevention on molecular mechanisms, molecular targets and human relevance of tea constituents . Among numerous mechanism studies, EGCG binds and inhibits the anti-apoptotic protein Bcl-xl , a protein involved in both cancer cell and normal cell survival . EGCG suppressed AOM-induced colonic premalignant lesions in mice, interfered with EGFR signaling , and inhibited hepatocyte growth factor-induced cell proliferation in human colon cancer cells . EGCG has shown inhibition of mitogen-activated protein kinases (MAPK), cyclin-dependent kinases, growth factor-related cell signaling, activation of activator protein 1 and NF-κB, topoisomerase I and matrix metalloproteinases. In human, the pharmacological concentration are typically at least 10 μmol/L .
Our lab studied EGCG induced stress signals in HT-29 human colon adenocarcinoma cells and found that EGCG inhibited HT-29 cell growth with an IC50 of approximately 100 μM, and the dose levels higher than that showed apparent nuclear condensation and fragmentation, and the study concluded that EGCG caused damage to mitochondria and JNK mediated EGCG-induced apoptotic cell death . EGCG was also found to increase AP-1 luciferase activity dose-dependently up to 100 μM , reduce LPS-induced IκB alpha phosphorylation . Additional study in our group demonstrated that combining sulforaphane and EGCG exerted synergistic effects in HT-29 AP-1 human colon carcinoma cells . To investigate possible Nrf2-mediation, EGCG were orally dosed to C57BL/6J and C57BL/6J/Nrf2(−/−) mice. The liver and small intestine were analyzed using Affymetrix mouse genome 430 2.0 array. Gene expression showed that 671 Nrf2-dependent and 256 Nrf2-independent genes were regulated by EGCG in liver, and 228 Nrf2-dependent and 98 Nrf2-independent genes are regulated by EGCG in intestine. This study pointed out that the EGCG chemopreventive effects may be mediated by Nrf2, at least partially .
- Medicinal Garden
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Here’s more on growing and using borage.
Fisetin from strawberries, apples
Fisetin is a flavone found in various plants such as Acacia greggii, Acacia berlandieri, Euroasian smoketree, parrot tree, strawberries, apple, persimmon, grape, onion, and cucumber . Fisetin has been found to alleviate aging effects in the yeast or fruit fly , exert anti-inflammatory effect in LPS-induced acute pulmonary inflammation and anti-carcinogenesis effects in HCT-116 human colon cancer cells . Fisetin is also a potent antioxidant and modulates protein kinase and lipid kinase pathways . Fisetin, along with other flavonoids such as luteolin, quercetin, galangin and EGCG, induced the expression of Nrf2 and the phase II gene product HO-1 in human retinal pigment epithelial (RPE) cells which could protect RPE cells from oxidative-stress-induced death with a high degree of potency and low toxicity and reduced hydrogen peroxide (H2O2)-induced cell death . A recent study by Khan et al found dual inhibition of PI3K/Akt and mTOR signaling in human non-small cell lung cancer cells by fisetin . Fisetin inhibited Wnt signaling through the modulation of beta-catenin expression, transcriptional activity and of the subsequent expression of Wnt target genes . Other studies found fisetin decreased cell viability with G1-phase arrest and disrupted Wnt/β-catenin signaling , exhibited an inhibitory effect on the abilities of adhesion, migration, and invasion, and significantly decreased the nuclear levels of nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) . Fisetin was also found to help to overcome the multidrug resistance caused by the high expression of the plasma membrane drug transporter P-glycoprotein (P-gp), which is associated with an elevated intracellular glutathione (GSH) content in various human tumors .
Genistein from soybean
Genistein is an isoflavone originates from a number of plants such as lupine, fava beans, soybeans, kudzu, and psoralea, Flemingia vestita, and coffee. Functioning as antioxidant and anthelmintic, genistein has been found to have antiangiogenic effects (blocking formation of new blood vessels), and may block the uncontrolled cell growth associated with cancer, most likely by inhibiting the enzymes that regulate cell division and cell survival (growth factors). Genistein’s activity was chiefly functioned as a tyrosine kinase inhibitor by inhibiting DNA topoisomerase II . In vitro and in vivo studies show that genistein has been found to be useful in treating leukemia [.
Estrogen receptors are over-expressed in around 70% of breast cancer cases (ER-positive). Binding of estrogen to the ER stimulates proliferation of mammary cells, with the resulting increase in cell division and DNA replication. Estrogen metabolism produces genotoxic waste, which may cause disruption of cell cycle, apoptosis, DNA repair, and forms tumor. Genistein can compete with 17β-estradiol (estrogen) to bind to estrogen receptor and shows higher affinity towards estrogen receptor β than towards estrogen receptor α , where estrogen receptor functions as a DNA-binding transcription factor that regulates gene expression. Genistein was confirmed to increase the rate of growth of some estrogen receptor in breast cancer and the rate of proliferation of estrogen-dependent breast cancer when not co-treated with an estrogen antagonist . In colon cancer, genistein is thought to contribute to reduced colonic inflammation in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis . Our lab previously investigated genistein and found that genistein possibly involved in JNK pathway in inducing AP-1 activity .
Gingerol from gingers
Gingerol is the active component of fresh ginger with distinctive spicyness. Gingerol has been studied for its anticancerous effects for the tumors in colon , breast and ovarian , and pancreas . A recent review by Oyagbemi et al summarized the mechanisms in the therapeutic effects of gingerol . In short, gingerol has demonstrated antioxidant, anti-inflammation, and antitumor promoting properties, decreases iNOS and TNF-alpha expression via suppression of IκBα phosphorylation and NF-κB nuclear translocation . Treating K562 cells and MOLT4 cells with gingerol, the ROS levels were significantly higher than control groups, inducing apoptosis of leukemia cells by mitochondrial pathway . On human hepatocarcinoma cells, gingerol, along with 6-shogaol were found to exert anti-invasive activity against hepatoma cells through regulation of MMP-9 and TIMP-1, and 6-shogaol further regulated urokinase-type plasminogen activity . Topical application of 6-shogaol, another active component from ginger is more effective than 6-gingerol and curcumin in inhibiting 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced transcription of iNOS and COX-2 mRNA expression in mouse skin, which may justify further in vitro and in vovo studies .
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Kaempferol from tea, broccoli, grapefruit
Kaempferol is a natural flavonol isolated from tea, broccoli, Witch-hazel, grapefruit, Brussels sprouts, apples, etc . Kaempferol has been studied for pancreatic cancer , and lung cancer . It has been investigated for its antiangiogenic, anticancer, and radical scavenging effects . Kaempferol, displayed moderate cytostatic activity of 24.8 – 64.7 μM in the cell lines of PC3, HeLa and K562 human cancer cells . To et al studied kaempferol as aryl hydrocarbon receptor (AhR) antagonist showing inhibition of ABCG2 upregulation, thereby reversing the ABCG2-mediated multi-drug resistance, which may be useful for esophageal cancer treatment . Luo et al found that kaempferol induces apoptosis in ovarian cancer cells through the activation of p53 in the intrinsic pathway . Yang et al reported that kaempferol inhibited quinine reductase 2 with an IC (50) value of 33.6 μM for NF-κB activity . In a study by Niestroy et al, kaempferol was studied on benzo[a]pyrene (BaP) mediated effects on Caco-2 cells on concerted effects on the expression of AhR and Nrf2 pathway components . In that study, BaP, quercetin and kaempferol activated Nrf2 pathway by induction of Nrf2, and its target genes NQO1, GSTP1, GSTA1, and GCLC. However, in spite of their own induction potential for Nrf2, both quercetin and kaempferol counteract the effects of BaP on expression of AhR, AhRR, Nrf2, GSTP1 and NQO1 .
Kaempferol showed very low bioavailability of approximately 2% in earlier study . Using Madin-Darby canine kidney (MDCK) cell monolayers, kaempferol was shown to be a breast cancer resistance protein (Bcrp, Abcg2) inhibitor and may also be a Bcrp substrate, which may represent one possible mechanism for the low bioavailability of kaempferol .
Lycopene from tomato
Lycopene is a bright red pigment and phytochemical from tomatoes, red carrots, watermelons, and red papayas. It demonstrates antioxidant activity and chemopreventive effects in many studies, especially for prostate cancer. Poorly solube in water, lycopene has high solubility in organic solvents. Its anti-cancer property is attributed to activating cancer preventive enzymes such as phase II detoxification enzymes . Lycopene was found to inhibit human cancer cell proliferation, and to suppress insulin-like growth factor-I-stimulated growth. This may open new avenues for lycopene study on the role of the prevention or treatment of endometrial cancer and other tumors . Lycopene also possesses inhibitory effects on breast and endometrial cancer cells , prostate cancer cells , and colon cancer cells . However, in a study conducted by Erdman and group using xenocraft prostate tumors into rats, it was found that the tumors grew more slowly in those given whole dried tomato powder but not in those given lycopene, which may indicate that lycopene may be an important component in tomato but not the only component in tomato that actively suppressing the growth of the prostate cancer .
Phenethyl Isothiocyanate (PEITC) from cruciferous vegetable
PEITC, along with sulforaphane from cruciferous vegetables, such as watercress, broccoli, cabbage, etc., have been studied for induction of apoptosis in cell lines. PEITC has shown very strong potency against melanoma. It has been intensively studied for chemoprevention against breast cancer cells , non-small cell lung cancer , cervical cancer, osteogenic sarcoma U-2 OS , prostate cancer, and myeloma cell lines . PEITC induces apoptosis in some cell lines that are resistant to some currently used chemotherapeutics drugs.
PEITC induced apoptosis in highly metastatic human non-small cell lung cancer L9981 cells via Caspase-3 activation , leading to cell cycle arrest at the G2/M phase by modulation of cyclin B1 expression, where MAPK/AP-1 pathway was the target . In vitro and in vivo data support that PEITC, as well as sulforaphane, induced G2/M cell cycle arrest, apoptosis of cell death of myeloma cells . In cervical cancer cells, PEITC was found to increase the expression of the death receptors (DR4 and DR5), cleaved caspase-3, induced caspase-8 and truncated BID, down-regulated the ERK1/2 and MEK phosphorylation while maintaining the expression of JNK and phospho-p38 MAPK . PEITC was also studied for cytotoxicity in a human liver hepatoma cell line (HepG2-C8) along with I3C, DIM, and sulforaphane, and it turned out that PEITC was more toxic than I3C and DIM In human prostate cancer DU 145 cells, PEITC induced apoptosis mediated by the activation of caspase-8, -9, and -3-dependent pathways . PEITC induced substential increase in the activation of caspase-3, -8, -9, cleavage and degradation of PARP, and apoptosis dose- and time-dependently, accompanied by the caspase-independent downregulation of Mcl-1, Akt inactivation, and activation of JNK . Using human osteogenic sarcoma U-2 OS cells, PEITC, along with benzyl isothiocyanates (BITC), caused growth inhibition, inhibited cell cycle regulatory proteins, promoted Chk1 and p53, induced apoptosis and poly(ADP-ribose)polymerase (PARP) cleavage . Wang et al found that cells with mutant p53 are more sensitive to cytotoxicity induced by PEITC than those with wild-type protein, which may be a novel target for cancer chemoprevention .
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