Norcantharidin and Analogs: Anticancer Agents - Essay Example

? Norcantharidin and analogues: Anticancer Agents Norcantharidin and analogues: Anticancer Agents Cancer is aleading killer in the world, since it has no cure. Many of the therapies used in the past only serve as short term cures. They, however, have many side effects on the patients. The chemotherapy is the most common control of cancer and side effects are quite severe. Patients complain of nausea after undergoing the process. Most of these anti-cancer agents are also not as effective as they should be, if the battle against cancer is to be successful. This has led researchers to create anti-cancer agents that take the structure of cancer, which will manage to structurally match the cancer agents and kill them in the process (Wang, et al, 2010). This paper reviews Norcantharidin and analogues: Anticancer Agents. Origin of Norcantharidin Concept The origin and development of Norcantharidin as an anticancer agent is from traditional medicine “Cantharididn”. In herbal medicine it is one of the forms of the medicines the people used in the past to treat warts and other diseases. This medicine was popular in China and Vietnam. Canthariding inhibits protein phosphates 1 and 2A (PP1 and PP2A). It is a scedaretion of the blister beetle, which many refer to as ‘Spanish fly’, commonly used in traditional medicine to treat Molluscum contagiosum virus (MCV) and warts. It is believed that this medicine also helped control the effects of cancer. Researchers used a combination of genomic and post genomic methods to identify genes affecting resistance and sensitivity of Cantharidin. Their findings made them want to explore their study further since the drug was not found to have any multidrug resistance phenotype. This made it a possible drug to use in treating refractory tumour This marked the beginning of the synthesis of the drug and its biological development to make an anticancer agent from it. The major reason for the study and development of Cantharidin was the need to eliminate the side effects of cancer chemotherapy. It is difficult to kill all cancer cells using chemotherapy as it affects the normal body cells, which increases drug resistance. This is because by the time the patient goes for another chemotherapy the cells have already adjusted to the treatment and tend to resist it. Cantharidin as an herbal medicine that did not show any signs of possible drug resistance was the best shot for health specialists in the fight against cancer. Like many herbal medicines it does not have any serious side effects on its users. Through molecular biology the drug has been enhanced to form what is now referred to as “Norcantharidin”. Structure In an attempt to treat cancer doctors have combined a series of proteins and phosphates and formed what they refer to as Norcantharidin called analogues. Analogues refer to proteins and other things with a structure almost similar to cancer. Several studies have been carried out to develop this in the recent years, and there have been reports of possible success. A study has found out that there exist several norcantharidin analogues that limit the functions of protein phospahatase 1 and 2A (Hill, et al, 2008). As a sort of anticancer agent, norcantharidin has been used to treat human cancers in China and other places since 1984 (Hill, et al, 2008; Thaqi, et al., 2010). In an attempt to increase the anticancer activity, a series of norcantharidin analogues has been synthesized and evaluated in anticancer activities recently (Thaqi, et al., 2010). The protein phosphatases are the ubiquitous enzymes that regulate many crucial biological functions. Of the serine-threonine phosphatases, two of the most prevalent are PP1 and PP2A (Wang, et al, 2010). So as to develop potential anticancer agents and investigate the anticancer mechanism of these compounds, the inhibitory activities of PP1 and PP2A of norcantharidin analogues have been studied as well (Liu & Chen, 2009). Interestingly, the ability of norcantharidin analogues to inhibit PP1 and PP2A correlates well with their anticancer activity against cancer cell lines (Liu & Chen, 2009; Wang, et al, 2010). Below are figures Fig1: Norcanthari Fig 2: Norcantharidin analogue Quantitative Structure-Activity relationships that relate to biological activities with structures of compounds have been used in the studies of the potential use of Norcantharidin and analogue as anticancer agents. Some researchers have reported that some of the Norcantharidin analogue contains inhibitory properties of PP1 and PP2A (Wang, et al, 2010). Functioning The notion behind the development of Norcantharidin analogue and their synthesis and biological use as potential anticancer agents is because some proteins are known to alter disease structures including cancer and even HIV/AIDS. The fundamental roles of Protein Phosphates in the synthesis of Norcantharidin analogue is to signal the pathways of eukaryotic cells and allow possible exploitation of these pathways. Cancer is one of the diseases that originate from irregular cellular signalling and altering the signals can help reduce the effects of cancer on humans. Cancer is the indisputable human’s most dreaded disease. Approximately one out of every five people die from cancer and the trend is a big concern to many people and research organizations. Treating cancer is complex as it includes a number of diseases with various initiating causes, several co-factors and various initiators. To add to the complicated nature of cancer it also has various results and effects on people’s bodies that are difficult to predict. Nevertheless, health practitioners and medical specialists know that cancer does not adhere to the normal cell division. Cancer cells grow and continue to proliferate in an uncontrolled way, which characterizes malignancy (Thaqi, et al., 2010). In healthy non-malignant cells, the cell cycle is a highly regulated process allowing the reproduction of cells by duplication of their contents, followed by division into two identical cells. In eukaryotic cells, division occupies only a small part of the cell cycle, during the rest of the time cells are in interface (Liu, et al. 2009). It is during interphase that DNA replication and other processes fundamental to cell cycle progression, including cell differentiation, gene expression and protein synthesis occur. For a cell to proceed successfully through the cell cycle it is important that each stage of the cell cycle be completed prior to entry into the next. This is regulated through a series of checkpoints. When a cell enters G1, normal cellular activity returns, including gene expression and protein synthesis. Many of the new cells formed now differentiate, and do not undergo further division. In the continuing cells, DNA replication occurs during the S phase, during which DNA content doubles and the chromosomes are replicated (Liu & Chen, 2009). These cells then enter the G2 phase before progressing to mitosis. During the M phase, the replicated chromosomes condense and the sister chromatids separate, which is easily seen under a microscope. It is here that division occurs and mitosis is complete when two daughter cells have formed (Hill, et al, 2008). Phosphate proteins help control the cell division of cancer cells, as a result serving as cancer anti agents. In conclusion, traditionally doctors used therapeutic techniques as anti-cancer agents. With time. However, they have come to learn that these techniques only serve to relieve the body of the pain that comes along with cancer. This is because cancer originates from abnormal cell division that causes various diseases and abnormalities in the body. To cure and stop disease the best option is always to reach at the source and cut it loose. This has made it essential for health practitioners and medics to develop and synthesis proteins for biological use as anticancer agents. The development of these chemical compounds using Protein phosphates has resulted in the concept of Norcantharidin and analogue. Various researches show that there is great potential of these protein phosphate compounds altering the cell division and growth of cancer and inhibit or reduce the cell division. This means that there is the possibility of success in cancer control through the use of Norcantharidins and analogues. References Hill, T. A., Stewart, S. G., Gordon, C. P., Ackland, S. P., Gilbert, J., Sauer, B., ... & McCluskey, A. (2008). Norcantharidin analogues: synthesis, anticancer activity and protein phosphatase 1 and 2A inhibition. ChemMedChem, 3(12), 1878-1892. Liu, D., & Chen, Z. (2009). The effects of cantharidin and cantharidin derivates on tumour cells. Anti-Cancer Agents in Medicinal Chemistry-Anti-Cancer Agents), 9(4), 392-396. Liu, F. Y., Li, Y., Peng, Y. M., Ye, K., Li, J., Liu, Y. H., ... & Zhou, L. T. (2008). Norcantharidin ameliorates proteinuria, associated tubulointerstitial inflammation and fibrosis in protein overload nephropathy. American journal of nephrology, 28(3), 465-477. Thaqi, A., Scott, J. L., Gilbert, J., Sakoff, J. A., & McCluskey, A. (2010). Synthesis and biological activity of ?-5, 6-norcantharimides: importance of the 5, 6-bridge. European journal of medicinal chemistry, 45(5), 1717-1723. Wang, Q., Zhang, L., Hu, W., Hu, Z. H., Bei, Y. Y., Xu, J. Y., ... & Zhang, Q. (2010). Norcantharidin-associated galactosylated chitosan nanoparticles for hepatocyte-targeted delivery. Nanomedicine: Nanotechnology, Biology and Medicine, 6(2), 371-381. Read More