Anticancer Efficacy of Curcumin Analysis

Anticancer Efficacy of Curcumin Analysis Nuclear factor-ÃŽ ºB (NF-ÃŽ ºB) is a transcription factor that is essential in the regulation of immune and inflammatory responses. 1 It influences a diverse target of gene expressions that regulate apoptosis, facilitate cell survival, proliferation, and differentiation. 1,2 Before cell stimulation, NF-ÃŽ ºB dimers that are located in the cytoplasm are inactive. 3 Prior to activation, NF-ÃŽ ºB dimers consisting of RelA, c-REL, and p50 are held in the cytoplasm by inhibitory ÃŽ ºB (IÃŽ ºB) proteins. 3,8 The IÃŽ ºB kinase (IKK) complex is activated by various extracellular signals such as proinflammatory cytokines and viral infections. 3,4 This IKK complex phosphorylates two conserved serine residues and targets NF-ÃŽ ºB-bound IÃŽ ºBs, which results in ubiquitin-mediated dissociation of IÃŽ ºB from NF-ÃŽ ºB, thus leading to translocation of activated NF-ÃŽ ºB into the nucleus. 2,7 The activation of NF-ÃŽ ºB promotes tumor invasion, metastasis, and allows malignant cells to escap e apoptosis. Consequently, many chemotherapeutic drugs have been found to activate NF-ÃŽ ºB, thus contributing to chemoresistance and chemotherapy failure. 3 Increasing evidence suggests that, the inhibition of NF-ÃŽ ºB activation can reduce chemoresistance and improve the effectiveness of chemotherapeutic agents. 3 Among the compounds that have been reported, curcumin was found to inhibit the activation of NF-ÃŽ ºB and thus, induce apoptosis in tumor cells. 6 Unfortunately, its clinical applications remains limited due to its poor bioavailability and low potency 6 , these prompted researchers to chemically modify curcumin in order to increase its potency against NF-ÃŽ ºB and cancerous cells. 8 In this issue, Qui et al . 8 reports progress in the synthesis and identification of new 4-arylidene curcumin analogues as a potential chemotherapeutic agent. Different kinds of 4-arylidene curcumin analogues were synthesized by coupling 1, 3-diketones curcumin analogues with various aro matic aldehydes in toluene with acetic acid, using piperidine as a catalyst (figure 1). The chemotherapeutic activities of the synthesized compounds were tested on the growth of A549 lung adenocarcinoma cells with curcumin used as control. The authors reported that majority of the 4-arylidene curcumin analogues exhibited potent anticancer activities against A549 growth with GI 50 in the range of 0.23 – 0.93 ÃŽ ¼M, while very poor antiproliferation activities of curcumin was observed at 15.23 ÃŽ ¼M. This shows a 10- to 60-fold increase in the potency of 4-arylidene curcumin analogues over the parent compound, curcumin. Remarkably, the cytotoxic activities of these newly designed curcumin analogues were not limited to A549 cells. The growth of other carcinoma cells H1944, squamous cells H157, and large carcinoma cells H460, were effectively inhibited by selected 4-acrylidene curcumin analogues, with GI 50 values at micromolar concentrations low to 0.07 ÃŽ ¼M. Likewise, in a r elated study, Zambre et al. 9 reported that copper(II) conjugates of Knoevenagel condensates of curcumin analogue showed inhibitory activities against human leukemic KBM-5 cells. Taken together, these two forms of curcumin analogues offer new possibilities at both ends as potential anticancer agents. One of the key curcumin targets that is important for the survival of cancer is IÃŽ ºB kinase (IKK), which regulates NF-ÃŽ ºB activation. 6 Activated NF-ÃŽ ºB is situated in the nucleus to promote transcription that is triggered by tumor-necrosis factor (TNFÃŽ ±). 1,5 Thus, Qiu et al. 8 used nuclear translocation of NF-ÃŽ ºB in response to TNFÃŽ ± as the main indicator to examine the mode of action of curcumin in comparison to 4-arylidene curcumin analogue. A549 cells were treated in a 384-well plate format with curcumin and its new analogue respectively, before the addition of TNFÃŽ ± to trigger nuclear translocation of NF-ÃŽ ºB p65 subunit. As a result, curcumin inhibited TNFÃŽ ± -induced nuclear translocation of NF-ÃŽ ºB with a mean IC 50 of 9.5 ÃŽ ¼M, which is consistent with the work of Kasinski et al . 4 Interestingly, most of the synthesized 4-arylidene curcumin analogue showed improved inhibitory activities against NF-ÃŽ ºB translocation with mean IC 50 values in the range of 1.0 – 4.9 ÃŽ ¼ÃŽÅ". This finding proved the superiority of the newly designed curcumin analogue over curcumin in blocking nuclear translocation of NF-ÃŽ ºB. Consequently, in a related paper, Zambre et al. 9 developed novel curcumin analogues that were synthesized using Knoevenagel condensation to convert enolic diketones of curcumin into non-enolizable ones. The synthesized compounds were examined for their potential in blocking TNFÃŽ ±-induced NF-ÃŽ ºB activation. It was reported that copper(II) conjugates of Knoevenagel condensates of curcumin showed greater potentials in blocking TNFÃŽ ±-induced NF-ÃŽ ºB activation than curcumin, confirming the potency superiority of curcumin analogues over the parental curcumin.

Personal response Assignment Example | Topics and Well Written Essays - 250 words

Personal response - Assignment Example When both male members of her family showed their concern over her relationship with Hamlet, she defends her love for Hamlet but follows the counsel of his father seeing the wisdom in his argument (Act I, Scene III). During her time, women were not allowed to have discourse with men. They merely followed. Ophelia’s discourse with Laertes and her father shows a woman who fights for the man he loves but it also shows a woman who can see reason and wisdom in her father’s arguments and that is why she obeyed him. Who is Ophelia? She is a woman who knows how to love and fight for her loves. She is reasonable and recognizes wisdom. She is a woman of strength and substance. She knows her duty. During those times Honor meant more than riches. In her need to protect her family’s honor she drowned herself. She could not contain within herself the thought of her fathers’ death – he died avenging her dignity and honor-- that she killed herself. Tragic! It also aims to scorn men for looking at women as mere toys and possessions. This is the Ophelia I

Mau Mau Insurgence. Strategic Assessment of Mau Mau Research Paper

Mau Mau Insurgence. Strategic Assessment of Mau Mau - Research Paper Example Kenyans were reacting to the oppressive nature of British rule, and especially to the confining boundaries that British officials had drawn for them in the political, economic, and social spheres.† The Kikuyu tribes had begun to surface their voice back in 1924 when Kikuyu Central Association (KCA) was formed to voice public anger politically. Later on, it was KCA that provided the foundations to Kenya Land Freedom Army (KLFA) or simply known to be LFA. The British settlers were blamed to exploit the powers conferred upon them through imperial rule and land acquisition of more than 43,000 square feet land from Kikuyu peasants. Forced nationalization of live stock and breach of women rights were among the major phenomenon which historically have contributed towards the formation of LFA. John Maina Kahihu from the Mau Mau's political wing said in a post independence interview, "In 1942 we had fought for the British. But when we came home from the war they gave us nothing." (Slaughter, 1999). In the backdrop of this political trust deficit insurrection and insurgence are supposed to be natural phenomenon. Moreover, the freedom of subcontinent states from British colonial rule through a long stretched political struggle in 1948 had already set a precedent for Kenyans. In 1950 Kikuyu tribes Led by Dedan Kimathi, had begun to formulate in the forests of Nairobi to start an armed resistance to British Colonial Empire. The assassination of Senior Chief Waruhui in October 1952 further deteriorated the political efforts for a peaceful solution. Governor declared the state of emergency in the country which gave unlimited powers to British authorities to detain the insurgents and put off the rebellion. The Mau Mau gang was predominately composed of Kikuyu tribesmen who were known for their brutality. To be a part of Mau Mau gang tribesmen had to take an oath to testify that they will endeavor for the ouster of British settlers and colonial rule. The gangs begin to enlarge in early second half of the 20th century. The oath was not considered a free choice by Mau Mau gangs rather they used severe atrocities against their own tribesman who refused to favour their version of British ouster. Mau Mau gangs run door to door campaigns to gather as much power as possible to launch a barbarous insurgency against the colonial rule. Such a movement, especially in a colonial state could not be tolerated long and even a strict British response to this insurgency was solicited by the Colonial Secretary and Governor. The British government planned and executed a successful counter insurgency strategy to tackle the Mau Mau. The major stakeholders of this Kenyan insurgence include the Kikuyu tribes, Dedan Kimathi, the leader of Mau Mau, other Kenyans who joined Mau Mau, the British Colonial authorities in Kenya, British settlers and British Home Office. Kikuyu tribes were gauged to be one fifth of the Kenyan population. They were the major contributor to this insurgence because they had suffered a lot in the past and had only fewer things to lose in case of a fresh bloodshed. Kikuyu tribes were the occupant of the most fertilized land in Kenya which was later on taken over by the British settlers. The president of Kenya African Union, Jomo Kenyatta tried to mollify the