Overview of Applications to Flavonoids to Cancer

Overview of Applications to Flavonoids to Cancer Flavonoids and its effect on the proliferation of the cells: Published date suggested that flavonoids have capability to inhibit phosphate protein kinases on their specific sites. Flavonoids interact with Akt/PKB (protein-kinase B), tyrosine kinase P1KC (protein-1 kinase C), PI3-kinase (phosphoinositide 3-kinase), and MAP (mitogen-activated protein) kinase signaling pathways. Flavonoids have been reported to activate and inhibit the effects on these signaling pathways by modulating of their gene expressions (Williams et al., 2004). Flavonoids inhibitory mechanism has been proved by altering their receptor phosphorylations or blocking growth factor receptor binding. Flavonoids also inhibit Fyn and Lck protein kinases, involved in T cell signaling transport (Calic et al., 2005). PI3K catalyze productions of PIP1 and PIP2. PIP3 may activate the PDK1 which stimulates the Akt/PKB. Of these effects PDK1 is essential for regulator of cell growth, proliferation, differentiation, migration and apoptosis. Bad, Bcl-2, and caspases proteins are responsible for apoptosis, these can be inhbitied by Akt pathway. Several data have been suggested that flavonoids directly inhibit the PI3K pathway by their interacting their ATP binding sites. MAPK pathway ((ERK2, JNK1 and p38) are responsible for releasing of many survival genes (c-Fos, c-Jun) and those genes which are involved in the antioxidant activity (detoxification enzymes, glutathione S-transferase, glutathione-reductase) have also been activated by low level of quercetin. Anti-cancerous properties of the flavonoids: Flavonoids also have anticancer activities by blocking their cellular mechanism. Flavonoids targets the cell cycle regulator proteins (cycline-dependent kinases and their inhibitors, protein p53 and Rb, E2Fs, ATM/ATR and surviving transition-controlling points G1/S and G2/M) (Sing et al., 2006). Flavopiridol properly inhibits the CDK1-and CDK2 cell regulating pathways (Vermeulen et al., 2003). Cell proliferation and cell viability ratio of the prostate cancer decreased with treatment of quercetin. Quercetin induced apoptosis with down-regulating mechanism of Hsp90 expression of proteins, resulting in the death of cancer cells by inhibiting the cellular growth. (Aalinkeel et al., 2008). Inhibiting cellular growth and DNA synthesis and blockage of cell cycle at S-phase in squamta cells have been reported with quercetin (Haghiac et al., 2005). Querecetin also prevents growth of nasopharyngeal cancer cells via arrest of cell cycle at G1/S phase (Ong et al., 2004). ERK (extracellular signal-regulated kinase) pathway stimulates the lung cancer which is derived from the A549 cell proliferation have been reported combine inhibitory effects of querecetin and kaempferol (Hung et al., 2007). Quercetin stimulates the protein expressions of p21 and p22 which inhibited the cell cycle in H epG2 cells (Mu C et al., 2007). Quercetin at the concentration of (248uM) down-regulates the mutantp53 expressions which is almost untraceable in the cell lines of the breast cancer. Negative control was too lower as compare to normal gene p53. Quercetin at the dose of 70 uM, having inhibiting activity on cell division, and trysine kinase activity, is an enzyme placed on the cell membrane and is involved in growth factors and signaling transduction in nucleus (Lamson et al., 2000). Scientific data have been reported that flavonoids especially the quercetin having oral anticancer properties. Quercetin inhibits the cellular growth and DNA synthesis depending the dose and timing of the administration. Quercetin induced apoptosis with treatment of caspase-3 proteins after 72 hours, and cell necrosis after 24-48 hours in SCC-9 cells. Flow cytometer studies confirmed cell cycle blockage at S-phase with the treatment of quercetin (Haghiac et al., 2005). Quercetin induced cell proliferation of B16-BL6 after 72 hours and also caused apoptosis in B16-BL6 cells and reduced the expressions of Bcl-2 and anti-apoptotic proteins (Zhang et al., 2000). Anti-apoptotic properties of the flavonoids: Flavonoids have been reported to induce apoptosis process by activating and modulating cellular signaling pathways resulting in death of pre-cancerous and maligne cells, which terminates cancer development or progression. Human prostate cancer cell line LNCaP, treated with different concentrations of quercetin shown to inhibited cell death after 24 hours. Inhibition of Akt survival signals have been activated in the treated cells. Rapid decrease in Ser 136 phosphorylation in Bad that is a Akt target have been reported with treatment of LNCaP and 100 uM of quercetin. Quercetin have been shown to reduce the Bcl-XL, Bx ratio and enhances translocation and multimeriation of Bax in the mitochondrial membrane; cytochrome-c released by translocation, and the caspase 3, 5, 9 proteins and PARB (poli(ADP-ribose)polymerase). Remarkably, quercetin does not induce cellular viability or apoptosis at same concentrations in normal prostatic epithelial cells (Zhanget al., 2000). Exposure of cells for longer time on quercetin induced apoptosis intervened by reduction of thymidylate synthase (Ong et al., 2004). Quercetin induced apoptosis in CNE2 and HK1 cells after 24 hours of treatment and treatment was continued when necrosis was observed. HeLa cells have been exposed on non-toxic flavonoid concentrations which slightly susceptible to TRAIL induced cell death. TRAIL mediated cytotoxicity in HeLa cells was increased by apigenin and ginstein but no effect have been documented with kaempfeol and quercetin (Leeet al., 2008). Luteoline induced cell cytotoxicity by suppressing PI3K/Akt (phosphattidylinositol 3-kinase), NF-kB (nuclear factor kappa B) and XIAP (X-linked inhibitor of apoptosis protein) and activates of apoptotic pathways, such as p53 protein (Lin et al., 2008 and Lopez-Lazaro., 2009). At high doses majority of the flavonoids suppressors AP-1 activity (activator protein 1) by MAPK (mitogen – activated protein kinase) pathway (Gopalakrishnan et al., 2006). Activation of cellular signaling pathways in cancer and flavonoids: Figures-9. Sources of inflammatory mediators and their origin Figure-7. Some diseases and cancers associated with reactive oxygen species (ROS) Conclusion: Oxidative stress brings the changes into the cells resulting in gene mutation which leads to the carcinogenesis. It brings direct or indirect intra and inter-cellular and intercellular transduction and transcription changes by antioxidants. The role of oxidative stress in carcinogenesis and tumor bearing conditions is complex and various mechanisms and substances are involved. Clinical evidence suggests that oxidative stress and inflammation linked to free radicles over generation may be the key factor in development of chronic diseases, insulin resistance, diabetes, cardiovascular and other diseases. Excessive nutrition, stress in combination with sedentary lifestyle, can independently result in overburden of glucose and fatty acid accumulation with musle, adipose tissue and pancreatic cells. All these factors lead to chronic inflammation resulting in chronic diseases. Published data suggested that the key role of polyphenolic compounds such as flavonoids as therapeutics agents in the inflammatory diseases including obesity, T2DM, cardiovascular diseases, neurodegenerative diseases cancer and aging. Flavonoids are the key modulators of inflammatory molecules. Flavonoids inhibits the AMPK one of the major pathway of inflammation and cancer. Activation of AMPK by flavonoids causes to increase the cancer cell apoptosis, inhibit cell proliferation and some studies suggested that it a neoplastic agent Furthermore, inflammation stimulates various inflammatory mediators, chemokine’s, cytokines, signaling transductions and transcriptional factors; overproduction for long periods may lead to chronic inflammation which in turn to chronic diseases such as neurological diseases and cancer. Better clarification of these mechanisms will be beneficial to the development of efficacious prevention and therapies of inflammation associated cancers. Moreover, effects of flavonoids at molecular mechanism and study also should be carried out on modulatory action; effects on transcription levels of the flavonoids should be studied. Fig-4. Anti-inflammatory activities of the flavonoids SOD- Superoxide dismutase 2- CAT- Catalase 3- GPx- Glutathione peroxidase 4- GR- Glutathione reductase 5- GST- Glutathione S-transferase. 6- ÃŽ ³GCS- ÃŽ ³-glutamylcysteine synthetase 7- NADPH:NQO1- quinone oxidoreductase-1. 8- HSP70- heat shock proteins. 9- MPO- myeloperoxidase 10- iNOS- inducible nitric oxidase synthase. 11- OH Hydroxyl radical. 12- O2 -superoxide radical. 12- MDA- Malondialdehyde 13- IL-2 interlukins-2 14- FMLP- Formyl-Methionyl-Leucyl-Phenylalanine. 15- TNF-ÃŽ ±- Tumor necrosis factor ÃŽ ±. 16- LTB4- Leukotriene B4. 17- LTC4- Leukotriene C4. 18- TXB2- Thomboxane B2 19. PGE2- Prostaglandins e2. 20- NF-ÃŽ ºB- Nuclear Factor Kappa Beta 21- ICAM-1- Intercellular Adhesion Molecule 22- VCAM-1- vascular cell adhesion molecule-1

A Boy’s Own Story -Book Review

Running head: Book Review Thomas Meyer SOCWK 330 Book Review Brief Summary A Boy’s Own Story is the story of the author’s, Edmund White, own self discover of his homosexuality in the 1940’s and 1950’s in America. A Boy’s Own Story is the first autobiographies in a three book series spanning the author’s late childhood throughout his adulthood. Edmund experiences a brief sexual relationship with Kevin, a slightly younger friend. Kevin and Edmund’s intimacy is presented as natural and untroubled, untouched by the internalized homophobia that will later plague young Edmund’s life. I was aware of the treacherous air vents above us, conducting the sounds we were making upstairs. Maybe dad was listening. Or maybe, just like Kevin, he was unaware of anything but the pleasure spurting up out of his body and into mine. † (White, 1982, pg. 17) Edmund’s father does not serve as a good role model. Edmund’s father was an adulterer, who later abandons Edmund’s mother for another woman. Edmund’s father abandons his responsibilities leaving the family without his financial support. Edmund acts on his desires and has sex with Mr. Beattie, an older school teacher of Edmund.After society pushes the ideals of homophobia on Edmund he decides to turn in Mr. Beattie, thus turning his back on someone who has shown him affection just like his father did to him and his family. A Boy’s Own Story ends with Edmund still unable to achieve a positive gay identity. His struggle to come to terms with his homosexuality is not over. Character’s Behavior Edmund’s evolution from adolescence evolved his understanding and acceptance of his homosexuality. He starts his first noted homosexual experiences with a younger male whose family was living with them.He does not seem conflicted with the guilt and internalized & externalized homophobia that latter plagues him. Book Review â€Å"I suffe red now. I felt isolated to the point of craziness, but with a faint recourse to melodrama, to a potential audience and attendant end to loneliness, for if I imagined complete despair I pictured it as an emptying of the theater, a feeling that the stalls and boxes would never be peopled again†¦Ã¢â‚¬  (White, 1982, pg. 136) Edmund desire to fit into his perceived norms of societies forges into him a conflict of character.He begins to seek out others for sex and affection. He hides his desires from everyone that knows him including a good friend of his because he fears rejection. In the end of the book Edmund is questioning the morality and position of religion and society on the issue of homosexuality. Theoretical Analysis One of the best known and accepted theories of homosexual identity development is by Cass. Cass developed a six stage identity development model. Edmund progresses through the stages in this first volume of his autobiography to the third stage.At the end of t he book Edmund seems to be still struggling with his homosexuality but has come to the realization that he is not the only one that has homosexual tendencies. (Cass, 1984) A psychoanalytic view of Edmund’s homosexuality would focus on his relationship with his father and mother. This approach may question if Edmund suffered from gender identity issues. Edmund calls himself a sissy and girly. Edmund compares himself to his sister who he sees as the athlete in the family that wins his father’s approval. Furthermore, Edmund states that when he was younger he had romantic feelings and desires for his father.Edmund tries to gain the affection of his father and later approval of his father. In conjunction to having an emotionally distant father he also had a mother who seemed more interested in being a socialite over being a mother. These issues can be looked at using classical Freudian techniques. Book Review I personally do not like the Freudian psychoanalytical perspectiv e because I feel the theories are not properly tested. I am also interested to see how Edmund’s childhood being raised in an affluent family may have had an impact on how he developed as an individual. I will need time and further study to get a better gripe of this issue.It was suggested in a Sociology class that there is a socioeconomic factor difference between the new rich and old money when it comes to the issue of homosexuality. According to the professor new rich like Edmund’s family where less tolerate because they do not feel as secure in their economic status and feel a need to seek approval from society whereas old money may just see homosexuality as a form of eccentricness and they do not need the approval of society. I am still seeking a theory to support her statement. Summary Edmund story is an interesting look into his mind. The book has the flow of a common thought processes.The story changes focus and direction at times to explore the story deeper. It is difficult not to be drawn into the story as I am sure was the intent of the author. I am interested in how Edmund further developed his personal identity and came to terms with his homosexuality. I will be continuing to read the next book of the series as I am sure it will be just as fascinating. I have grown in my understanding of the psychosis of guilt and homophobia. I feel a bit more at ease with myself and feel for others who have suffered from society’s concept of normal behavior. In many ways I saw myself in Edmund’s story.Book Review Reference: Cass, V. (1984, May). Homosexual Identity Formation: Testing a Theoretical Model. The Journal of Sex Research, 20, 143-167. Elizur, Y. , & Ziv, M. (2001, Summer). Family Support and Acceptance, Gay Male Identity Formation, and Psychological Adjustment: A Path Model. Family Process, 40, 125-144. Linda, G. , & Kimmel, D. (1993). Psychological Perspectives on Lesbian and Gay Male Experiences.. New York, NY: Columbia Uni versity Press. Troiden, R. (1979). Becoming Homosexual: A Model of Gay Identity. Psychiatry, 42, 362-373. White, E. (1982). A boy's own story. New York: Penguin Books.

The Horror Genre in Stories of Stevenson and Greene Essay

The Horror Genre in Stories of Stevenson and Greene R.L Stevensons The Body-Snatcher and Graham Greenes The End Of The party are both short stories that are a part of the horror genre, despite differing in many ways. Throughout this essay, I am going to compare the differences and the similarities between the two horror stories. I will assess the way the writers use certain aspects that are part of the horror genre to make their story have an impact on the reader and have the ability to captivate their reader and keep them engrossed in the story. I will be focusing on specific areas within each story including, setting, structure, atmosphere, suspense, endings and also the different types†¦show more content†¦The use of isolated areas can be associated with sinister goings on and can add again to the readers uneasiness and fear. Also innocent victims can make the reader feel scared and more vulnerable, as it demonstrates that bad things can happen to anyone. Twists in horror stories are very common and both these horror stori es contain different twists that can shock the reader. The Body-Snatcher is a more typical horror story containing many of these things that I have mentioned. On the other hand, The End Of The Party differs to The Body-Snatcher, with it being more to do with the mind and appearing quite everyday, and not containing as many of the typical horror components. But both The Body-Snatcher and The End Of The Party can be placed in the horror genre as they contain the vital components that make a good horror story. The Body-Snatcher is quite self-explanatory in the title and is about body snatching. It begins in the small parlour of the George at Debenham where we meet the main character, Fettes. Fettes has an encounter with someone from his past - Macfarlane, who he is obviously not pleased to see for reasons unknown to the reader at this stage. At the mention of Macfarlanes name Fettes became instantly sober, this immediately tells the reader of something that has gone on in the past that may have been unpleasant toShow MoreRelated Horror Stories by Stevenson and Greene Essay2672 Words   |  11 PagesHorror Stories by Stevenson and Greene Horror stories are an excellent traditional genre. This genre has been around for almost as long as stories have been told. In this generation there is not much that can really scare us, but what does actually make a good horror story? Horror stories need to have a good and intimidating storyline, it needs to play on peoples fears, it also needs to give its audience a real thrill and send chills down their spines. The horror story may be based

Discuss the Relationship Between the Principles of...

Discuss the relationship between the principles of training, physiological adaptations and improved performance The relationship between the principles of training and physiological adaptations has a significant impact on performance. Many factors need to be addressed in a training program to make it a successful one for a particular athlete and thus improve their performance. The first principles are warm up and cool down. The purpose of any warm up and cool down is to reduce the risk of injury and soreness. For this to be applicable, a warm up must be sustained for no less than 10min and for elite athletes, at least 30min. Included in this warm up must be stretching to loosen up the muscles. There are no physiological adaptations that†¦show more content†¦These adaptations are relevant because the body is being stressed which leads to more blood being needed by the working muscles. With this increase in stroke volume and cardiac output, it also increases the heart rate. Heart rate is the amount of times the heart beats per minute. This means that the heart is working hard and being progressively overloaded increases the efficiency and will improve the performance of the athlete. Another adaptation is oxygen uptake. When the body is being progressively overloaded oxygen uptake is really important because it is the amount of oxygen being delivered to working muscles. This amount increases when exercise begins but decreases as adaptations occur. This is very similar to lung capacity as lung capacity is the amount of air that the lungs can hold. Another physiological adaptation in relation to progressive overload is haemoglobin levels. Haemoglobin is the substance in the blood that binds to oxygen and transports it around the body. These levels are important because it’s telling us how much oxygen and blood is being used and directly relates to stroke volume and oxygen uptake. Muscle hypertrophy is a term that refers to muscle growth together with an increase in the size of muscle cells. For a sprinter this adaptation is very important because it indicates that the muscles have been stimulated and grown and anShow MoreRelatedAdl 01 - Principles and Practices of Management Study Material.Pdf Uploaded Successfully30836 Words   |  124 Pagesqwertyuiopasdfghjklzxcvbnmqwertyui Principles and Practices of Management ADL 01 opasdfghjklzxcvbnmqwertyuiopasdfgh jklzxcvbnmqwertyuiopasdfghjklzxcvb nmqwertyuiopasdfghjklzxcvbnmqwer tyuiopasdfghjklzxcvbnmqwertyuiopas Principles and Practices of Management dfghjklzxcvbnmqwertyuiopasdfghjklzx Amity Center for eLearning cvbnmqwertyuiopasdfghjklzxcvbnmq wertyuiopasdfghjklzxcvbnmqwertyuio pasdfghjklzxcvbnmqwertyuiopasdfghj klzxcvbnmqwertyuiopasdfghjklzxcvbn mqwertyuiopasdfghjklzxcvbnmqwerty uiopasdfghjklzxcvbnmqwertyuiopasdfRead MoreApplication of Observational Learning6241 Words   |  25 Pageshyperlink. 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