Below mentioned 5 Medicinal Herbs are recommended for Patients of Cancer to enable a complete and successful remission -
Along with these 5 Herbal Medicines, following documentation too shall be enclosed in the Parcel for easy reference of patient -
• Copy of Authentication Certificate of FAGONIA CRETICA issued by ARI (Govt of India)
• Diet Regimen to be followed by Patients of Cancer
• Method of Intake of all the Herbal Medicines
• Copy of Organic Certification of Products
1) Organic Fagonia (cretica) indica Tea - For Patients, daily dosage is 20 Gms per Day.
2) Organic Holy Basil Tablets - 1 tablet twice a day.
Holy Basil decreases tumorigenicity and metastasis of aggressive human cancerous cells. Its a medically proven antioxidant which fights very effectively against Cancer. Holy Basil Tablets are always included in all our medicine parcel for the ease of patients.
3) Organic Wheatgrass and Giloy Tablets - 1 tablet twice a day.
Role of Wheatgrass in Cancer : Wheatgrass helps in building a strong immune system, and the key to killing cancer cells is oxygen. To lead an aggressive fight against cancer the body needs to produce more oxygen. Wheatgrass contains Chlorophyll, which is considered the "blood of plants". The molecular structure of chlorophyll is similar to that of hemoglobin. Hemoglobin transports oxygen from the lungs to the rest of the body. Incorporating wheatgrass into the diet will help build and renew blood cells in the body and increase the oxygen available to fight the cancer cells. Chlorophyll and selenium also help build the immunity system. Furthermore, wheatgrass is one of the most alkaline foods known to mankind thus killing "cancer favoring envirnoment".
Role of Giloy in Cancer : Tinospora cordifolia has incredible immune-boosting properties, and its one of the reasons why it is so effective against cancer. A strong immune system is better able to identify any cancerous cells and eliminate them before they have a chance to grown and spread. Tinospora contain a chemical called dichloromethane, which is known to poison and kill cancerous cells.
Scientists have also found that Tinospora contain potent cancer-fighting antioxidants such as catalase, glutathione and superoxide dismutase thus enabling in the process of Remission with ease.
4) Organic Turmeric Powder - to be taken in the night as 2 Gms daily with 100 ML of Lukewarm (Almond Milk) / (Coconut Milk) / (any Fat Free Milk if both Almond and Coconut are not available).
With its cell-penetrating ability, Turmeric can cleanse the body at the most vital level to prevent cancers and protect tissues from damage imposed by cancer causing agents. It also prevents cancer cells from damaging DNA and reduces the side effects of chemotherapy.
5) Organic Spirulina Powder - It has to be taken as 2 Gms daily with Fresh 1 Glass of Water.
Spirulina is superior to plant proteins in that it is about 60% protein and is a complete protein. The fat content of Spirulina is loaded with the healthy fats like GLA , EPA, DHA and ALA, which are important Omega 3's. It is a super source of B vitamins, minerals and many beneficial pigments like beta carotene and chlorophyll.
Here is how Spirulina benefits a patient of Cancer :
a) Stimulates Natural Killer Cells and prevents cancer cells from growing.
b) It has been used in light therapy to target and kill cancerous cells
c) Greatly reduces free radicals
d) Keeps cancer cells in permanent remission
e) Suppresses tumor growth by suppressing new blood flow to the tumor
f) Enhances cellular uptake of trace minerals like selenium
g) Inhibits the growth of viruses like Epstein Barr
Although effective in killing cancerous cells, chemotherapeutic agents also induce kidney toxicity. Spirulina helped protect the kidneys from being damaged by cisplatin, in a study published in the December 2006 issue of "Cancer Chemotherapy and Pharmacology." The scientists also noted that spirulina did not decrease the effectiveness of chemo medication so its good in alleviating the side effects of chemo as well and it works in sync with Fagonia (cretica) indica Tea.
» Please do contact DR. AMIT NAKRA by sending an email - AsmiConsultancyHerbals@gmail.com or calling on +91 - 98961 - 72224 for all details regarding dispatching the Parcel of Fagonia (cretica) indica Tea, Indian Organic Turmeric Powder, Organic Wheatgrass + Giloy Tablet, Organic Spirulina Powder and Holy Basil Tablets at your address anywhere in world through DHL Express Cargo Service. Its received within 2-5 working days and email updates are sent every 12 hours with regard to the movement of Parcel. You can also track the movement of Parcel through waybill (issued by DHL) on www. DHL.com.
Fagonia (cretica) indica Tea is being widely known as a Herbal Treatment for Cancer. For more details on the same please do read as follows -
According to traditional knowledge Fagonia (cretica) indica has medicinal potential especially against cancer and tumors. An aqueous decantation (A.D) of the plant is a popular remedy for cancer in indigenous system of medicine and similar research was carried out in Aston University along with Rusell Hall Hospital in UK. Now the patients who went through chemotherapy during their treatment of Cancer, in some patients there was a huge drop in Hb levels. When the A.D. of Fagonia (Cretica) indica was given for a couple of days before the next course of chemotherapy it was quite impressive to observe that there was no change in the blood count (no myelo-suppression or reduction in the blood count or the Hemoglobin level) so there was no need of blood transfusion. Patient continued A.D of Fagonia (Cretica) indica during the rest of her treatment and showed excellent improvement. Her hair started growing back, skin color became normal and there was no need of blood transfusion over and above showed impressive improvement and regression of the Tumor.
In Western medicine, the focus is the eradication of the cancers cells once they have been diagnosed. Ayurveda is not a replacement for Western medicine. Once cancer has been diagnosed, all avenues of treatment, including conservative (allopathic) and complimentary approaches should be thoroughly investigated. Ayurveda will address prevention and underlying causative factors, while Western medicine will deal with the symptoms, which in some cases can be life-threatening. Through this Mail, we will discuss the cause, treatment, and prevention of Cancer exclusively from the Ayurvedic perspective.
In Ayurveda, cancers are not treated solely as a physical condition. The relationship between mental, emotional, physical, and spiritual factors are all identified when treating cancer. The general definition of cancer in Ayurveda is when the cells have forgotten their memory of normal and proper function. They have lost the smirti value (cellular memory). Without the memory of proper function the cells have no rules.
In Ayurveda, the cause of all disease is termed pragya pradh which, when translated, means the mistake of the intellect: the intellect decides to see itself as separate from the underlying field of consciousness from which we all come. Quantum physics recognizes the existence of such a unifying field and Ayurveda recognizes that field as our own consciousness. It is the goal of Ayurveda to re-establish the experience of consciousness or silence in every cell in the body. Stress, pollution, lifestyle, chemotoxins, and fear are major factors that strip the silence of consciousness from our experience. When the silence is lost on a cellular level the cells become disconnected from their roots in consciousness. They lose their memory and begin to function at random in a survival fashion just to stay alive.
With a cancer diagnosis, a common treatment approach response is to attack the cancer as the enemy, visualizing cancer cells exploding, or killing them with radiation or chemotherapy. This approach does have its place and certainly should be investigated. But in Ayurveda the approach works on the basis of peace, not war. History has proven that for every war that has ever been fought, there comes a time to make peace and shake hands. The cancer cells are a part of the body that have lost their memory. They are not necessarily bad cells that must be destroyed, they are cells that have lost their way and need to be reconnected to their roots of consciousness. Overuse of antibiotics in the past 40 years is proof of what happens to cells when you try to kill them. Bacteria, in the name of survival, have become resistant to the once very lethal antibiotics. Cancer cells that are relentlessly sought after to be destroyed will also find ways to resist the attackers, and in many cases become stronger and more committed to their cause of survival. This is not to say there is never a need for chemotherapies.
The next expression of the mistake of the intellect is triggered by emotional constrictions that separate the mind and body in the name of survival. Fear is the first emotion we feel when we lose the experience of consciousness on a physical level. Consciousness, which of course is lively in every cell, is stored in the heart as a substance calledÂ ojas.Â OjasÂ is considered to be the physical expression of consciousness. This experience of consciousness is the only source of true happiness. When we lose it because of fear of getting hurt, the body employs the sympathetic nervous system's fight-or-flight response to protect the delicate feelings of the heart. These emotional constrictions manifest in the body physically by separating the consciousness (ojas) in the heart from the memory (smirti) of the cells. Again the cells begin to function at random. Depending on the kinds of stress, chemical exposure, and/or genetic susceptibility,Â BreastÂ cancer or other related cancers can be the result.
Stress is probably the biggest factor in the loss of cellular memory. Stress has a powerful effect on physical and mental responses in the body and has recently been traced to be the cause of 80% of all disease, including cancer. Stress triggers stress-fighting hormones that can be produced 24 hours a day depending on the severity and duration of the stress. These stress-fighting hormones are degenerative and produce free radicals as waste products, which are believed to be the leading cause of aging, disease, cancer, and death. Stress also creates mental and muscular tension, a compromised blood supply, and an increase in waste production. All these factors curtail circulation and communication on a cellular level. If cells cannot get blood in and waste out effectively, then the communication to and from cells breaks down. Soon, the cells will lose their memory of normal function and will have to alter their programming in the name of survival. If gross cellular circulation is decreased, cells will begin to reproduce in an alternative method. If the genetic predisposition is cancer, or if exposure to environmental pollutants has been excessive, then cancer can be how an individual breaks down. In Ayurveda, this same cause can trigger a variety of symptoms, depending on individual genetic susceptibility.
Cause of Cancer in Ayurveda Definition
In Caraka Samhita, Chapter XIII in Chikitsasthanam, eight types of abdominal disease or udara-roga are described. Typically Cancer are caused by the accumulation of doshas (either vata, pitta, or kapha), or by intestinal obstruction (which is how four of the eight are described). It is clearly stated that Cancer arises from a weak digestive agni (power of digestion) and a resultant increase of malas (waste products). If food is unwholesome, as are processed, frozen, rancid, or improperly cooked foods, doshas accumulate, affecting prana (life force), apana (downward force), and agni (digestive force). Waste products build up, energy becomes depleted, and the passages of prana going up and malas (waste) going down and out becomes obstructed.
Excerpts from the Research:
Researchers from Aston University, Birmingham, and Russells Hall Hospital, Dudley, found that Fagonia (cretica) indica / Dhanvyas contains potent anti-cancer agents that act singly or in combination against the proliferation of cancer cells.
Laboratory tests showed they arrested the growth of cells within five hours of application and caused them to die within 24 hours and we are hereby providing the conclusion of Reasearch for your reference -
WHAT RESEARCH SAYS -
"Researchers have discovered the extracts found in Fagonia cretica have not only halted the spread of Cancer Cells but also caused a limiting action on them thereby enabling the remission of Cancer among the Folk women of asian countries"
Researchers at Aston University and Russells Hall Hospital in the United Kingdom have discovered an extract in a common herbal tea that may halt the spread of cancer.
The ingredient comes from a plant, fagonia cretica, also known as Virgon's mantlem. The plant has traditionally been used in parts of rural India and Pakistan to help people fight cancer. What had been dismissed as a folkloric remedy now seems to be true. What's more, men and women who drink the tea do not report the same side effects associated with other, more aggressive remedies advocated by modern medicine, like chemotherapy or radiation. Many people who choose to treat their cancers with those methods suffer from difficult, uncomfortable side effects, like hair and weight loss as well as a drop in blood count.
Helen Griffith and Armutul R. Carmichael led the study. They tested the plant extract and found that it killed cancerous cells in tissue without damaging the other, healthy cells.
Researchers hope to discover in the future what particular compound or element in the plant is responsible for its cancer-fighting success. Dr. Caitlin Palframann, a policy manager at the Breakthrough Cancer, "Some of the most important cancer-fighting drugs are originally derived from plants."
Following genotoxic stress, an intact DNA damage response (DDR) is necessary to eliminate lethal and tumorigenic mutations. The DDR is a network of molecular signalling events that control and coordinate DNA repair, cell cycle arrest and apoptosis. An impairment in the DNA damage response represents a double-edged sword, where on one side loss of repair mechanisms can drive tumorigenesis and on the other, can affect sensitivity to genotoxic chemotherapy.
The tumour suppressor protein, p53, plays a pivotal role in regulating the cellular response to stress and damage signals. Several of the cell signalling pathways involved in the DDR and cell differentiation converge with p53Â and loss of p53 functionality is common in more than 50% of cancers. In response to stress signals, post-translational modifications of p53 such as phosphorylation, drive its nuclear translocation and subsequent target gene transcription. Normally, upon DNA damage, p53 is rapidly stabilised by the DNA damage sensor, ATM, via phosphorylation of serine-15 within the p53 N-terminus activation domain. Consequently, dissociation of the MDM2-p53 repressor complex, prevents monoubiquitination of p53 and its degradation. This in turn increases p53 half-life and activates its transcriptional program.
Important p53 transcriptional targets include cell cycle control genes such as p21 (WAF1/CIP1), 14-3-3Ïƒ and cyclin G, and pro-apoptotic genes such as BAX. The cyclin dependent kinase inhibitor, p21, is a direct regulator of the cell cycle, inducing growth arrest in G1-phase of the cell cycle by binding to and inhibiting the activity of cyclinD-CDK2/4 complexes. Increased transcription and translation of p21 prevents cyclinD-CDK2/4 mediated phosphorylation of retinoblastoma protein (pRb), thus, inhibiting E2F transcriptional activity and cell cycle progression to S-phase.
However, p53-independent growth arrest and cell death has also been observed following ionizing radiation and DNA damage (the cell death machinery governed by p53. Recently, it has been shown that in response to DNA damage, the transcription factor FOXO3a is vital to initiating growth arrest. Moreover, induction of DNA damage by ionizing radiation, activates FOXO3a and increases its nuclear translocation. The FOXO3a-dependent activation of Bim and Fas ligand expression is associated with induction of apoptosis, and is observed independently of p53, highlighting a potential FOXO3a-mediated response to DNA damage. As well as this, FOXO3a is a regulator of metabolic homeostasis, via its interaction with Akt and AMPk signaling pathways. Pharmacological modulation of these pathways has been shown to induce cell death in cancer cells via FOXO3a-dependent mechanisms.
Targeting the cell cycle to induce arrest pharmacologically is known to be effective in restricting tumour growth in vitro and in vivo, particularly in transformed cells that have an aberrant response to genotoxic and cellular damage. We have investigated the potential forÂ Fagonia creticaÂ to inhibit the growth of cancer cells via a DNA damage driven response.Â Fagonia creticaÂ is a herbaceous plant found in arid, desert regions of Pakistan, India, Africa and parts of Europe. It is a common plant used in local medicine as a herbal tea to remedy cancer. However, mechanism(s) of action forÂ Fagonia creticaÂ extracts on cancer cells have not been investigated. Herein, we show that an aqueous extract ofÂ Fagonia creticaÂ induces growth arrest and apoptosis in human cancer cells by inducing DNA damage and activation of p53 and FOXO3a.
In this study we report mechanisms of Fagonia cretica aqueous extract-induced cytotoxicity in cancer cells. Local medical practitioners use Fagonia cretica for treating a wide variety of ailments, including cancer. This substance is well tolerated and does not exhibit adverse effects like vomiting, diarrhea or alopecia, which are common side effects of standard cytotoxic therapy. To the authors' best knowledge, this study is the first time that cytotoxic activity towards human cancer cell lines has been described. Herein, we have shown that an aqueous extract of Fagonia cretica is able to induce cell cycle arrest and apoptosis in wild type p53 MCF-7 and mutant p53 MDA-MB-231 cells, while only exerting a limited effect on primary HMEpC at high concentrations and extended treatment time. We have also demonstrated that cell cycle arrest may be associated with induction of DNA damage and in MCF-7 cells, via activation of the ATM/p53-mediated DNA damage response. Interestingly, the requirement of p53 activation is not essential for cytotoxicity, as we have shown with siRNA p53 knockdown in extract-treated MCF-7 cells, and the significant treatment effects on mutant-p53 MDA-MB-231 cells. In contrast, extract-induced cytotoxicity is shown to be dependent on induction of FOXO3a expression, in both cell types.
Induction of cell cycle arrest occurs in response to various stresses including DNA damage. Stabilisation and activation of p53 can occur as a result of serine-15 phosphorylation by ATM/ATR in the presence of DNA damage. This in turn allows for p53 nuclear translocation and activation of transcriptional targets such as p21 and BAX to regulate cell cycle control and apoptosis. According to our results, extract treatment of MCF-7 cells induced arrest in G1-phase of the cell cycle and triggered apoptosis, which may be controlled by p53-mediated transcription of the CDK-inhibitor p21 and pro-apoptotic BAX. This result is consistent with the literature on tamoxifen which describes G1-arrest induced by DNA damage in cancer cells. Blockade of extract-induced p53 expression using a phamacological inhibitor of ATM/ATR, caffeine, attenuated loss of cell viability in MCF-7 cells. This suggests activation of the DNA damage response is driving p53-mediated effects in extract-treated MCF-7 cells. Indeed, it was further shown that extract treatment may induce double strand breaks in MCF-7 cells, detectable by comet assay and by the presence of γ-H2AX, however, other forms of DNA damage can increase comet assay results and γ-H2AX expression. This DNA damage response pathway is well characterised and provides a potential mechanism by which extract treatment induces cell cycle arrest and apoptosis in MCF-7 cells. Mutations in p53 that generate a non-functional phenotype are common in tumours, and although frequency is lower in breast tumours than in other tumour types, mutant status is associated with a more aggressive disease and mediates tumour cell survival.
It is therefore important that drugs are developed that can specifically target cancer cells independent of their p53 status. We used siRNA against TP53 to knockdown p53 expression in p53 wild-type MCF-7 cells and then treated the cells with aqueous extract. Inhibition of p53 expression did reduce the cytotoxic effect of treatment but did not fully abrogate the loss of cell viability due to extract treatment. This suggests that p53 mediated cytotoxicity is an additional effect seen in cells that carry a functional form of p53 but is not vital to the treatment effect. We confirmed this effect in MDA-MB-231 breast cancer cells, which carry a mutant, non-functional form of p53. Indeed, we demonstrated that extract-induced cytotoxicity in MDA-MB-231 cells is less than in MCF-7 cells but remains significant at 24h. It has been shown previously that cells can arrest in the G1-phase of the cell cycle independent of the p53-p21 axis, and also that apoptosis can be initiated without p53 activation. Extract-treated MDA-MB-231 cells also underwent G0/G1 arrest but induction was delayed until 24 hours providing further support for the notion that p53 expression in MCF-7 cells drives extract-induced growth arrest. It has been shown previously that p53 functionality governs kinetics of cell cycle arrest in response to DNA damage thus providing a mechanism by which absence of p53 could delay onset of cell cycle arrest. It was evident that double strand breaks were induced in both MCF-7 and MDA-MB-231 cells upon extract treatment suggesting a shared mechanism driving cell death. Indeed, it has been shown recently that in response to DNA damage, p53-mutant cells undergo p53-independent cell cycle arrest and apoptosis, offering a significant therapeutic strategy for p53-mutant cancers.
Members of the forkhead class ‘O’ (FOXO) family of transcription factors have been implicated in tumorigenesis. In particular FOXO3a has been shown to function as a tumour suppressor in ERα-positive and negative breast cancers. It has also been reported recently that nuclear localisation of FOXO3a and subsequent transcriptional activity is a marker of good prognosis among breast cancer patients. As well as this, FOXO3a has been show to regulate cell cycle arrest and apoptosis in response to DNA damage, via activation of transcriptional targets such as Bim, p27 and Fas-L . We report here that FOXO3a expression is increased in both MCF-7 and MDA-MB-231 cells in response to extract treatment. Furthermore, suppression of extract-induced FOXO3a expression using FOXO3 siRNA, attenuated cytotoxicity in MCF-7 cells and completely abrogated cytotoxicity in MDA-MB-231 cells. Interestingly, levels of FOXO3a protein expression correlate with time points where significant DNA damage is exhibited, suggesting FOXO3a expression may be directly linked to DNA damage. This provides evidence for FOXO3a-dependent cell cycle arrest and death in breast cancer cells that works independently of p53 following extract treatment. Although FOXO3a involvement in oxidative stress and survival signal withdrawal-induced transcriptional activity is well documented, the role of FOXO3a in response to DNA damage, is relatively unclear. FOXO3a is activated as a survival response to energy depletion and can drive autophagy and apoptosis. Indeed, treatment with Fagonia cretica reduced ATP levels significantly in MDA-MB-231cells within 3 hours (data not shown). Energy depletion can occur as a result of excessive PARP activation due to DNA damage. Therefore, it is possible that DNA damage may induce a metabolic stress, which directly activates FOXO3a. Furthermore, FOXO3a driven transcription of DNA repair genes, including PARP, may further deplete cellular NAD+ and ATP and lead to cell death.
Why do HMEpC remain viable following extract treatment compared to MCF-7 or MDA-MB-231 cells? Cytotoxic agents are known to induce DNA damage in normal cells as well as cancer cells. However, fast growing cells are more susceptible to DNA damaging agents due to the greater probability of more sites being exposed on DNA within replicative cycles and, in addition, cancer cells frequently have defective repair pathways resulting in DNA damage being sustained. While normal cells may also up-regulate FOXO3a in response to energy depletion and DNA damage, they are less dependent on glycolytic metabolism than cancer cells. They may be less energetically challenged in the presence of Fagonia cretica because of the potential to use oxidative phosphorylation as an additional energy source.
Its been displayed above for the first time that an extract of Fagonia cretica induces cell cycle arrest and apoptosis in two phenotypically distinct cancer cell lines. Extract activity involves DNA damage and p53-induction but is not fully dependent on p53 functionality. In addition, extract treatment induces FOXO3a expression which may be attributed to DNA damage directly or induction of DNA repair pathways. We also demonstrated that FOXO3a expression is required for extract activity in the absence of functional p53. This provides a novel mechanism by which an aqueous extract of Fagonia cretica, used extensively in India and Pakistan, can kill cancer cells.
Citation: Lam M, Carmichael AR, Griffiths HR (2012) An Aqueous Extract of Fagonia cretica Induces DNA Damage, Cell Cycle Arrest and Apoptosis in Breast Cancer Cells via FOXO3a and p53 Expression. PLoS ONE 7(6): e40152. doi:10.1371/journal.pone.0040152
Editor: Pranela Rameshwar, University of Medicine and Dentistry of New Jersey, United States of America
Received: April 6, 2012; Accepted: June 1, 2012; Published: June 27, 2012
The authors would like to thank Mohammed Shuwaikan, Birmingham University and Dr Marcus Cooke, Leicester University, for advice on the comet assay.
Conceived and designed the experiments: ML HRG. Performed the experiments: ML. Analyzed the data: ML HRG. Contributed reagents/materials/analysis tools: HRG ARC. Wrote the paper: ML HRG.
- Zhou BBS, Elledge SJ (2000) The DNA damage response: putting checkpoints in perspective. Nature 408: 433â€“439.
- Helleday T, Petermann E, Lundin C, Hodgson B, Sharma RA (2008) DNA repair pathways as targets for cancer therapy. Nature Reviews Cancer 8: 193â€“204.
- Helleday T, Lo J, van Gent DC, Engelward BP (2007) DNA double-strand break repair: From mechanistic understanding to cancer treatment. DNA Repair 6: 923â€“935. doi:
- Sionov RV, Haupt Y (1999) The cellular response to p53: the decision between life and death. Oncogene 18: 6145â€“6157. doi:
- Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) P53 mutations in human cancers. Science 253: 49â€“53. doi:
- Lakin ND, Jackson SP (1999) Regulation of p53 in response to DNA damage. Oncogene 18: 7644â€“7655. doi:
- Appella E, Anderson CW (2001) Post-translational modifications and activation of p53 by genotoxic stresses. European Journal of Biochemistry 268: 2764â€“2772. doi:
- Banin S, Moyal L, Shieh SY, Taya Y, Anderson CW, et al. (1998) Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 281: 1674â€“1677. doi:
- Haupt Y, Maya R, Kazaz A, Oren M (1997) Mdm2 promotes the rapid degradation of p53. Nature 387: 296â€“299. doi:
- Moll UM, Petrenko O (2003) The MDM2-p53 interaction. Molecular Cancer Research 1: 1001â€“1008. doi:
- McVean M, Xiao HY, Isobe K, Pelling JC (2000) Increase in wild-type p53 stability and transactivational activity by the chemopreventive agent apigenin in keratinocytes. Carcinogenesis 21: 633â€“639. doi:
- Tokino T, Nakamura Y (2000) The role of p53-target genes in human cancer. Critical Reviews in Oncology Hematology 33: 1â€“6. doi:
- Cheng W-L, Lin T-Y, Tseng Y-H, Chu F-H, Chueh P-J, et al. (2011) Inhibitory Effect of Human Breast Cancer Cell Proliferation via p21-Mediated G(1) Cell Cycle Arrest by Araliadiol Isolated from Aralia cordata Thunb. Planta Medica 77: 164â€“168.
- Broude EV, Swift ME, Vivo C, Chang BD, Davis BM, et al. (2007) p21(Waf1/Cip1/Sdi1) mediates retinoblastoma protein degradation. Oncogene 26: 6954â€“6958.
- Yoshida K, Miki Y (2010) The cell death machinery governed by the p53 tumor suppressor in response to DNA damage. Cancer Science 101: 831â€“835. doi:
- Lei H, Quelle FW (2009) FOXO Transcription Factors Enforce Cell Cycle Checkpoints and Promote Survival of Hematopoietic Cells after DNA Damage. Molecular Cancer Research 7: 1294â€“1303. doi
- Yang J-Y, Xia W, Hu MCT (2006) Ionizing radiation activates expression of FOXO3a, Fas ligand, and Bim, and induces cell apoptosis. International Journal of Oncology 29: 643â€“648.
- Gross DN, Wan M, Birnbaum MJ (2009) The role of FOXO in the regulation of metabolism. Current Diabetes Reports 9: 208â€“214.
- Burgering BMT, Medema RH (2003) Decisions on life and death: FOXO Forkhead transcription factors are in command when PKB/Akt is off duty. Journal of Leukocyte Biology 73: 689â€“701. doi:
- Chiacchiera F, Simone C (2010) The AMPK-FoxO3A axis as a target for cancer treatment. Cell Cycle 9: 1091â€“1096. doi:
- Ben Sahra I, Laurent K, Loubat A, Giorgetti-Peraldi S, Colosetti P, et al. (2008) The anti-diabetic drug metformin exerts an anti-tumoral effect in vitro and in vivo through a decrease in cyclin D1 level. International Journal of Obesity 32: S17â€“S17.
- Shah MA, Schwartz GK (2003) Cyclin-dependent kinases as targets for cancer therapy. Cancer chemotherapy and biological response modifiers 21: 145â€“170.
- Shapiro GI, Harper JW (1999) Anticancer drug targets: cell cycle and checkpoint control. Journal of Clinical Investigation 104: 1645â€“1653. doi:
- Blasina A, Price BD, Turenne GA, McGowan CH (1999) Caffeine inhibits the checkpoint kinase ATM. Current Biology 9: 1135â€“1138. doi:
- Said HM (1969) Hamdard Pharmacopoeia of Eastern Medicine: Sri Satguru Publications. 558 p.
- Pellegata NS, Antoniono RJ, Redpath JL, Stanbridge EJ (1996) DNA damage and p53-mediated cell cycle arrest: A reevaluation. Proceedings of the National Academy of Sciences of the United States of America 93: 15209â€“15214. doi:
- Boehme KA, Kulikov R, Blattner C (2008) P53 stabilization in response to DNA damage requires Akt/PKB and DNA-PK. Proceedings of the National Academy of Sciences of the United States of America 105: 7785â€“7790. doi:
- Liontas A, Yeger H (2004) Curcumin and resveratrol induce apoptosis and nuclear translocation and activation of p53 in human neuroblastoma. Anticancer Research 24: 987â€“998.
- Ichikawa A, Ando J, Suda K (2008) G1 arrest and expression of cyclin-dependent kinase inhibitors in tamoxifen-treated MCF-7 human breast cancer cells. Human Cell 21: 28â€“37. doi:
- Fragkos M, Jurvansuu J, Beard P (2009) H2AX Is Required for Cell Cycle Arrest via the p53/p21 Pathway. Molecular and Cellular Biology 29: 2828â€“2840. doi:
- Kastan MB, Bartek J (2004) Cell-cycle checkpoints and cancer. Nature 432: 316â€“323. doi:
- Gasco M, Shami S, Crook T (2002) The p53 pathway in breast cancer. Breast Cancer Research 4: 70â€“76.
- Lim LY, Vidnovic N, Ellisen LW, Leong CO (2009) Mutant p53 mediates survival of breast cancer cells. British Journal of Cancer 101: 1606â€“1612. doi:
- Thompson T, Danilenko M, Vassilev L, Studzinski GP (2010) Tumor suppressor p53 status does not determine the differentiation-associated G(1) cell cycle arrest induced in leukemia cells by 1,25-dihydroxyvitamin D(3) and antioxidants. Cancer Biology & Therapy 10: 344â€“350.
- Kim S-H, Singh SV (2010) p53-Independent Apoptosis by Benzyl Isothiocyanate in Human Breast Cancer Cells Is Mediated by Suppression of XIAP Expression. Cancer Prevention Research 3: 718â€“726. doi:
- Al-Mohanna MA, Al-Khodairy FM, Krezolek Z, Bertilsson PA, Al-Houssein KA, et al. (2001) p53 is dispensable for UV-induced cell cycle arrest at late G(1) in mammalian cells. Carcinogenesis 22: 573â€“578.
- McNamee LM, Brodsky MH (2009) p53-Independent Apoptosis Limits DNA Damage-Induced Aneuploidy. Genetics 182: 423â€“435. doi:
- Yang JY, Zong CS, Xia WY, Yamaguchi H, Ding QQ, et al. (2008) ERK promotes tumorigenesis by inhibiting FOXO3a via MCM2-mediated degradation (vol 10, pg 138, 2008). Nature Cell Biology 10: 370â€“370.
- Zou Y, Tsai W-B, Cheng C-J, Hsu C, Chung YM, et al. (2008) Forkhead box transcription factor FOXO3a suppresses estrogen-dependent breast cancer cell proliferation and tumorigenesis. Breast Cancer Research 10.
- Accili D, Arden KC (2004) FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell 117: 421â€“426. doi:
- Habashy HO, Rakha EA, Aleskandarany M, Ahmed MAH, Green AR, et al. (2011) FOXO3a nuclear localisation is associated with good prognosis in luminal-like breast cancer. Breast Cancer Research and Treatment 129: 11â€“21. doi:
- Tran H, Brunet A, Grenier JM, Datta SR, Fornace AJ, et al. (2002) DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein. Science 296: 530â€“534. doi:
- Essers MAG, Weijzen S, de Vries-Smits AMM, Saarloos I, de Ruiter ND, et al. (2004) FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK. Embo Journal 23: 4802â€“4812. doi:
- Yin L, Kharbanda S, Kufe D (2009) MUC1 oncoprotein promotes autophagy in a survival response to glucose deprivation. International Journal of Oncology 34: 1691â€“1699.
- Herceg Z, Wang ZQ (2001) Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 477: 97â€“110. doi
- Gao J, Yang X, Yin P, Hu W, Liao H, et al. (2012) The involvement of FoxO in cell survival and chemosensitivity mediated. International Journal of Oncology 40: 1203â€“1209. doi: