Anticancer Properties of Piper Betle Leaves Active Compounds

However, the majority of known anti-cancer drugs target normal cells as well. Methotrexate, formerly known as amethopterin, is an antimetabolite used in the treatment of some forms of cancer (Shacter and Law, 1956). It inhibits the function of dihydrofolate reductase (DHFR) by tightly binding to the enzyme. Following this slow interaction between methotrexate and DHFR, an enzyme-NADPH-inhibitor complex is formed (Stone et al., 1984). Therein, DHFR is rendered unable to catalyze the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate (Anderson, 2017). Tetrahydrofolate is an important methyl group shuttle in the de novo synthesis of purine and pyrimidine nucleotides and some amino acids (Barbara and Hiroshi, 2002). Therefore, eliminating it from cells is a good therapeutic strategy against cancer cells, as it would limit the de novo synthesis of purines and pyrimidines (Lane and Fan, 2015). Inhibiting the function of DHFR by its competitive inhibitor methotrexate is one such good therapeutic strategy, as it would disable DHFR from converting dihydrofolate into tetrahydrofolate. However, some types of cancer cells had acquired some forms of resistance against methotrexate (Hans et al., 2011). Equally important, methotrexate should be administered in well established low doses, because it affects

According to the oral cancer foundation, “Chemotherapy is the use of chemicals to destroy cancer cells. Chemotherapy works by interfering with the cancer cell's ability to grow. It is one of the three main methods utilized to treat cancer.” With cancer being a potentially fatal disease it is important to diagnose it as soon as possible. the oncologist have to study the chemicals used so that they can determine what chemicals will treat the cancer or disease the best and what chemicals can be mixed together without any major side effects. The drugs can be divided into groups based on how they work, their chemical structure, and their relationship to other drugs.

Earlier studies on mice have shown that the poison can specifically attack and destroy tumor cells.

Norcantharidin (NCTD), the demethylated analogue of cantharidin, has been used to treat human cancers in China since 1984. It was recently found to be capable of inducing apoptosis in human colon carcinoma, hepatoma and glioblastoma cells by way of an elusive mechanism.1 Norcantatharidins and their analogues are synthetic anticancer agents which have been used in various different procedures for the inducing growth arrest and apoptosis of tumour cells and also provide therapeutic and adjuvant therapeutic applications in the treatment of cancer agents.2 This report will discuss the various different NCTD that are currently being studied, highlighting the synthesis of these NCTD and their various biological pathways that are taken in order to inhibit the growth of the correspondent cancer cell. In particular NCTD induced apoptosis of the hepatoma cells will be considered and also highlighting the different views with the synthesis of the particular NCTD and also the effectiveness of the methodology and its observations in response to other NCTD and their mechanism in attacking the hepatoma cell site.

Cancer unlike other illnesses is very unique in the fact we have to accept a certain level of toxicity well above that of any other group of pharmacologic agents. It is the toxicity of these agents which is the single most important factor preventing their use in doses that could often be curative. Ultimately the utility of most chemotherapy drugs depends on their therapeutic-to-toxic ratio, comparing the good and bad effects (Alwood et al, 1997). Other variables include the severity, predictability and reversibility of side effects. Although we are learning a lot more about the predictive side effects of many individual cancer drugs, most cancer patients require multi-drug therapies. Cancer patients often have chemotherapy regimens consisting of three or four different compounds along with other supportive therapy.

In vitro: R406 (1 μM or 5 μM) treatment reduced proliferation, migration and induced apoptosis in multiple myeloma (MM) cell lines [2]. R406 specifically blocked Fc receptor signaling in human B-cells, neutrophils, and macrophages with EC50 values of 48 nM, 33 nM, and 111 nM, respectively [1].

Cancer, the uncontrolled, rapid and pathological proliferation of abnormal cells is the growing public problem whose estimated worldwide new incidence is about 6 million cases per year. It is one of the most dreaded diseases of the 20th century and spreading further with continuous and increasing incidence in 21st century. This is the second leading cause of human death after cardiovascular diseases in developing as well as advanced countries. Although there are many therapeutic strategies including chemotherapy and radiotherapy, high systemic toxicity and drug resistance limit the successful outcomes in most cases

Such drugs are known as PKC inhibitors. This includes staurosporine, a microbial alkaloid and precursor to many novel PKC inhibitors which compete at PKC's ATP binding site. Newer drugds like N-benzoyl-staurosporin and -hydroxystauro-sporin improve selectivity and demonstrated better therapeutic effect in vivo. (21) The problem for existing PKC inhibitors is that they are relatively non-selective in their actions. In the future better drugs can be developed if they target specific isozymes in order to differentially inhibit PKC functions. (21) Some other researchers study the down stream products of PKC pathway, like vimentin, as a anti-cancer therapeutic target. For example, withaferin-A increases apoptosis and vimentin cleavage in vimentin expressing tumor cells and it has been proved that this drug has pronounced anti-antiogenic effect with little adverse effect in non-proliferating endothelial cells. (22) It also significantly blocks soft tissue sarcoma growth and

[57] A study conducted in 1981 by Horton et al. in which a single-agent therapy (melphalan) was compared to two combined therapies (5-fluorouracil + methyl-CCNU) and (5-fluorouracil + methyl-CCNU + streptozocin) actually concluded with survival times being similar between the three treatment regimens. Meanwhile, toxicity for two and three-drug combinations was significantly higher than for single drug treatment using mephalan. The study concluded that further research needs to be done for suitable treatments for patients with advanced pancreatic cancer.

Chemotheraputic drugs used in cancer treatment can be administered as a single agent or in combination (combination chemotherapy). It is known that the combination works better because different drugs work by different mechanisms and thus decreasing the chance of developing of resistant cancer cells. Also, combination allows the use of each drug at its optimal dose without side effects that can’t be tolerated by the patient. Sometimes combination chemotherapy is used to reduce symptoms and increase quality of life. As many things in this life, combination is a double edged sword may lead to serous side effects and risks and which could be reversible or irreversible.

Gemcitabine (2,2-difluoro 2-deoxycytidine, dFdC) is a deoxycytdine analog; a prodrug with activity against non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), ovarian and pancreatic cancers (Hertel et al., 1990; Braakhuis et al., 1995; Boven et al.,1993; Merriman et al., 1996; Jansen et al., 1995) Pancreatic cancer tumor [1 & 2 ref]. Nowadays gemcitabine is signified as a single agent in the treatment of patients with metastatic pancreatic cancer [2], (2,2-difluoro 2-deoxycytidine, dFdC) is an analogue of cytosine arabinoside (Ara-C) from which it vary structurally due to its fluorine substituents on position 29of the furanose ring [ref 1].

The ligand library is created to a total number of hundred natural phytochemicals which were collected with respect to anticancer activity based on the literature survey on Graviola. Lipinski Rules were followed for the study. • Not more than 5 hydrogen bond donors (nitrogen or oxygen atoms with one or more hydrogen atoms). • Not more than 10 hydrogen bond acceptors (Nitrogen or Oxygen atoms).

Our previous studies have shown that pristimerin possesses ability to suppress cell growth, induce apoptosis and inhibit metastasis in different colon cancer cells, including HCT-116 cells [19, 20]. These activities were accompanied with down-regulation of the expression of various genes including cyclin D1, Bcl-2 and Bcl-xl, all of which genes are NF-κB-dependent genes [19]. Therefore, in order to further understand antineoplastic activities of pristimerin, we investigated the in vivo and in vitro effects of pristimerin on the activity of NF-ĸB signaling pathway in HCT-116 cell line and xenograft

With the aim of developing efficacious and less toxic PI3K/mTORC inhibitors, the compounds we tested on a panel of pancreatic cancer cell lines in dose dependent way demonstrated that both dual PDK1/Aurora A inhibitors SA16 and IB35 are able to impair cell growth and migration and that they are not toxic at micromolar range to normal human pancreatic cells human embryonic kidney cells. The two compounds show a very similar activity but present some different results, such as the activity on cell proliferation in BxPC3 cells and on cell migration in AsPC-1 and BxPC3 cells. This could be explained by the different inhibitory profile possessed by SA16 that, as suggested by their in vitro IC50, inhibits with higher potency Aurora A compared to PDK1 whereas IB35 inhibits PDK1 preferentially.

Jiang-Tao Li, Jiu-Liang Zhang, Hui He, Zhi-Li Ma, Zhi-Kui Nie, Zhen-Zhen Wang, and Xiao-Gen Xu are affiliated with the College of Food Science and Technology, Huazhong Agricultural University & Key Laboratory of Environment Correlative Dietology, and the Ministry of Education, all in China. Their study of corn peptide effects on liver tumors in mice was funded by a grant from China’s National Natural Science Foundation and National “863” Program. They undertook this study to examine the effects of plant-derived chemicals on cancer. Cancers can be a result of any combination of dietary insufficiency, environmental factors, and/or genetic components. However, up to 95% of cancers are thought to be the result of diet and other lifestyle factors rather than the result of genetic factors (Bhanot et al 2011). The authors recognize this fact and there is a proliferation of naturally based products to boost immune function and combat tumor growth and development. Corn proteins (CPs) are widely and readily available as they are by-products of the expansive corn products market. Because previous work with CPs had shown positive physical affects (such as lowering blood pressure and mitigating the harmful effects of alcohol on the liver), the authors chose to examine how CPs might modulate tumors and the immune systems of mice.