Anti-Cancer

10-Deacetyl baccatin III is an intermediate in the synthesis of the chemotherapeutic drug, paclitaxel (taxol). It is produced by and isolated from Taxus baccata. 10-Deacetyl baccatin III is an immiscible organic compound.

5-Fluorouracil (5-FU) is a uracil analog that has a fluorine atom on the fifth carbon position. It acts as a strong anti-cancer agent where its metabolization disrupts both RNA and DNA synthesis. 5-FU metabolites, Fluorodeoxyuridine triphosphate (FdUTP) and fluorouridine triphosphate (FUTP), imitate uracil and are incorporated into RNA strands which effectively inhibits further synthesis.

Inhibition of DNA synthesis by 5-FU occurs through thymidylate synthase inhibition. A metabolite produced by 5-FU metabolism, fluorodeoxyuridine triphosphate (FdUTP), bind to the nucleotide binding site of thymidylate synthase. Halting this enzyme’s activity significantly diminishes deoxythymidine monophosphate (dTMP) production which consequently depletes dTMP within an organism.

8-Hydroxyquinoline is an organic compound that is used as a RNA inhibitor, anti-cancer agent and bidentate chelating agent. In vitro studies against Escherichia coli had shown 8-hydroxyquinoline inhibiting RNA polymerase activity. The enzyme’s activity was inhibited by chelating manganese, magnesium or zinc cofactors. Activity of 8-hydroxyquinoline toward RNA polymerase is broad and inhibits the synthesis of vertebrate RNA as well as proteins.

8-Hydroxyquinoline has also been used as an immobile chelating agent to remove transition metals, alkali and alkaline cations from solutions or within organisms. Its capability to bind the positively charged metals has been shown in vivo to inhibit proteasome activity in tumor cells by transporting copper ions into malignant cells. Halting proteasome activity was observed in vitro and in vivo with decreased cancer growth due to apoptosis.

Acalabrutinib (ACP-196) is an irreversible inhibitor of Bruton’s tyrosine kinase (BTK), which is responsible for the maturation of B-cells. Its high selectivity to bind the residue Cys481 in the active site of BTK is a sought after feature for oncology research. Studies on mice and human cells demonstrate the high affinity of ACP-196 and its low affinity toward similar proteins in T-cell maturation.

Acriflavine HCl is a compound predominantly used in cellular biology for fluorescence staining. It intercalates between the base pairs of DNA and RNA. Among the acridine dyes, acriflavine has the highest affinity for DNA. Acriflavine stains eukaryotic cells exceptionally well in humic substance environments. It provides a robust experimental consistency and reduces the effect of minor experimental errors. The binding of acriflavine to DNA can be observed from a characteristic red shift in an absorption spectrum. While having a high affinity for DNA, acriflavine is limited to euchromatin for both DNA and RNA.

Acriflavine has also been found to inhibit heterodimeric transcription factors, specifically called hypoxia-inducible factors (HIFs). Studying the hyperactivity of HIFs has become a popular in oncology research, where chemicals like acriflavine are used to disrupt HIF activity of malignant cells. HIFs are activated in hypoxic conditions and promote angiogenesis to alleviate stress. They are normally regulated through proline and asparagine hydroxylation. Acriflavine halts HIF activity, specifically by binding to a subdomain of HIF-1α and HIF-2α.

Actinomycin D is an antineoplastic antibiotic from Streptomyces species that inhibits cell proliferation by acting as a cytotoxic inducer of apoptosis against tumor cells, binding to DNA and inhibiting RNA polymerase activity. Actinomycin is also used in plant tissue culture to inhibit plant growth through tissue deformation where it also acts as an RNA-synthesis inhibitor. Along with its fluorescent derivative, 7aminoactinomycinD (7-AAD), Actinomycin is used to stain GC-rich regions of DNA for microscopy and flow cytometry applications.

Albendazole is a benzimidazole derivative typically used as a comprehensive antiparasitic belonging to the anthelminthic group and works by disrupting microtubule formation. Microtubule disruption diminishes glucose transport which increases glycogen catabolism. Eventually, this net loss of energy results in tissue death.

The resulting tissue death caused by microtubule formation is a sought after mechanism in oncology research. In vitro research of albendazole on HNSCC (head and neck squamous cancer cells) had shown cell cycle arrest in G2/M stage, resulting in apoptosis. Disruption of microtubule formation also prevented malignant cell migration.

Amygdalin is a glucoside derived from almonds and apricot kernels. While it was originally suggested that amygdalin is an anticancer agent, it is avoided due to its cyanogenic properties. Upon being metabolized by β-glucosidase enzymes, amygdalin produces hydrogen cyanide, which is cytotoxic on tumor cells. Amygdalin is freely soluble in aqueous solution and is used to study cytotoxic effects of cyanide on cancer cells and can be useful in identification and analysis of maltases, emulsins, and β-glucosidases.

Artesunate is a synthetic compound that is highly employed for its anti-malarial capabilities and is currently studied for its applications in oncology research and surgical procedures. In anti-malarial studies, it has been shown to disrupt EXP1 activity, which is a glutathione transferase responsible for cell detoxification in Plasmodium falciparum. Artesunate activity has been shown to be enhanced when co-administered with amodiaquine HCl.

In oncology research, Artesunate is used to arrest cancer growth in the G2/M phase and upregulate proteins p21 and Beclin1. These proteins are mainly related to apoptosis with p21 being a regulator of the process and Beclin1 playing a role in cell death by autophagy. Artesunate has also been shown to form an endoperoxide bridge which generates carbon radicals that dismantle the cell. However, the observed radical formation is dose and time dependent.

Artesunate has been shown to provide organ damage reduction in rats exposed to hemorrhagic shock. Administration of ART occurred after resuscitation and did not function as a preventative. Artesunate operates by decreasing cell apoptosis through protein kinase B (PKB) stimulation and glycogen synthase kinase inhibition. Cell survival is also enhanced by nuclear factor kappa B (NfkB) suppression, diminishing proinflammatory cytokine synthesis.

Baicalin is a flavone glycoside formed from the glucuronidation of baicalein. It has an array of properties which include promoting cell survival and bolstering the immune system. One of the effects that baicalin produced with in vitro studies of pathogens and in vivo studies on rats and mice was an elevation in cell survival, which implied the prevention of cell death due to induced apoptosis or the accumulation of oxidative species. Apoptotic repression occurred in rats due to a decreased expression of proteins within the CHOP (C/EBP homologous protein) pathway. Stimulating the synthesis of endothelial nitrogen oxides (eNOS) and other nitrogen oxides quell oxidative stress with the termination of free radicals.

Additionally, protective effects of baicalin have specifically diminished injury in the hippocampal area. Baicalin has been shown to stimulate the expression of Bcl-2 (B-cell lymphoma-2) which regulates apoptosis. It has also been shown to decrease miR-497 expression and cleave caspase-3 protein synthesis. These play roles in regulating gene expression and nervous system cell apoptosis respectively.

Enhancing the immune response with baicalin has proven effective in two ways. One observed effect was the induction of IFN-γ cytokine production in mice, a cytokine which activates macrophages and MHC II (major histocompatibility complex II) expression. Lysozyme bacteriostatic duration was shown to increase when exposed to increasing concentrations of baicalin.

Bakuchiol is a terpenophenolic compound extracted from the plant Psoralea corylifolia. Bakuchiol has been used as an oral antibiotic, anti-tumor agent and for the protection of liver and bone tissue. It has also been used as an insulin enhancer to counter hyperglycemia and hyperlipidemia for in vivo research on mice and rats. Within these studies, bakuchiol inhibited phospho-tyrosine protein phosphatase type 1B (PTP1B), DNA polymerase and topoisomerase II. Inactivity of these three enzymes greatly reduced PTPB1 activity, which has been found to suppress insulin signaling.

Antibiotic and anti-tumor uses of bakuchiol have been shown to be correlated to suppression of DNA synthesis. As a bactericidal agent, bakuchiol has been proven to be robust in vitro and is functional at many pH values as well as in the presence of organic acids. Bakuchiol terminates bacteria and malignant cells by generating intracellular reactive oxygen species (ROS), dismantling bacterial cells and compromising tumor cell mitochondria. Conversely, bakuchiol has also been shown to preserve liver function by inhibiting ROS that cause lipid peroxidation and the use of glutathione, an antioxidant.

The bone preserving effects of bakuchiol are related to its high binding affinity for estrogen receptor alpha (ERα). It has been shown that bakuchiol stimulates ERα to promote bone protective pathways.The pathways controlled by ERα increase alkaline phosphatase, calcium concentration, estradiol concentration and a decrease in inorganic phosphate level.

Bithionol is an anti-parasitic compound used for oncology research and molecular biology research. It induces apoptosis in cancerous cells occurs through activating proteolytic caspases. These caspases inactivate PARP-1(Poly [ADP-ribose] polymerase 1) which triggers an intrinsic pathway for apoptosis. Intrinsic apoptotic pathways result in compromising mitochondria and in this case by decreasing transmembrane potential. Reactive oxygen species then accumulate and rupture the mitochondria, releasing cytochrome c an apoptotic inducer.

Bithionol has been used to better understand enzyme allosteric regulation and the mechanism of soluble adenylyl cyclase inhibition, a bicarbonate sensor. Bithionol has been shown to occupy the bicarbonate binding site on soluble adenylyl cyclase. It has also been utilized in research to elucidate the role of mitochondrial potassium channels in preventing ischemia reperfusion injuries in mice.

Bleomycin A5 hydrochloride is a compound part of the glycopeptide antibiotic family. It is currently used in oncology research for its strong stimulatory and inhibitory effects. Bleomycin A5 greatly reduces telomerase activity, hindering the proliferation of malignant cells. It has also been shown to induce in vivo fibrosis and inflammation by generating peroxynitrites, a strong oxidizing agent.

Bleomycin A5 stimulates downstream apoptosis by increasing cysteine-aspartic acid protease-3 (caspase-3) activity, tumor protein 53 (p53) production and transforming growth factor beta 1 (TGF-beta 1) formation. These proteins induce apoptosis directly or indirectly by halting cell growth.

Bleomycin Sulfate is an anti-cancer agent isolated from Streptomyces verticillus. Bleomycin is a mixture of bleomycin A2 and bleomycin B2, in an approximately 2:1 ratio, respectively. However, the ratio varies by lot number.

Bleomycin is used against Hodgkin’s lymphoma. Its mechanism is not well understood; however, it is though that bleomycin chelates metallic ions causing a decrease in enzyme stability. The enzymes react with oxygen and produce free radicals, ultimately causing single-stranded breaks in deoxyribose sugars of DNA.

Brefeldin A is an antibiotic derived from Penicillium brefeldianum. It is an anti-cancer agent which disrupts protein transport and causes apoptosis of tumor cells. Brefeldin A disrupts the function of the Golgi apparatus and blocks Golgi-COPI activity. ER vesicles are prevented from fusion with the Golgi and are secretion is inhibited. Additionally, Brefeldin A is an ARF inhibitor, sphingomyelin cycle activator, and caspase-3 activator. It has been shown to induce apoptosis in leukemia cells and colon cancer cells.

Camptothecin is an alkaloid compound used as an anti-cancer agent. It is a topoisomerase I inhibitor in DNA synthesis. Camptothecin has been shown to bind and stabilize a topoisomerase I-DNA complex in vitro, preventing the enzyme from reannealing DNA strands. This inhibition specifically effects the S-phase of cell development and ultimately results in apoptosis due to damaged DNA.

Camptothecin is produced by endosymbiotic fungi, from the division Ascomycota (Phycomycete), that are present in the tree Camptotheca acuminata which is native to southern China. Camptothecin (Mappia foetida), (GoldBio Catalog # C-565) has also been isolated from fungi on Mappia foetida (Nothapodytes foetida), a plant common to India.

Camptothecin is an alkaloid compound used as an anti-cancer agent. It is a topoisomerase I inhibitor in DNA synthesis. Camptothecin has been shown to bind and stabilize a topoisomerase I-DNA complex in vitro, preventing the enzyme from reannealing DNA strands. This inhibition specifically effects the S-phase of cell development and ultimately results in apoptosis due to damaged DNA.

Camptothecin is found in Mappia foetida (Nothapodytes foetida), a plant native to eastern India. The compound itself is produced by an endosymbiotic Ascomycota (Phycomycete) fungi. Camptothecin (Camptotheca acuminata), (GoldBio Catalog # C-705) has also been produced by endosymbiotic fungi present in Camptotheca acuminata, which is a tree predominantly found in southern China.

Camptothecin sodium is sodium salt of an alkaloid compound camptothecin, which is used for cancer research. Camptothecin is produced from endosymbiotic Ascomycota (Phycomycete) fungi present in the tree Camptotheca acuminata or the plant Mappia foetida.

Camptothecin sodium is a topoisomerase I inhibitor in DNA synthesis. It has been shown to bind and stabilize a topoisomerase I-DNA complex in vitro, preventing the enzyme from reannealing DNA strands. This inhibition specifically effects the S-phase of cell development and ultimately results in apoptosis due to damaged DNA.

Carboplatin is an alkylating agent that is used as a chelating agent as well as a chemotherapeutic compound for its antineoplastic effects. While the exact mechanism of antineoplastic activity is still not well understood, it is believed to behave similarly to cisplatin which binds DNA and prevents its transcription and replication.

Carboplatin is also believed to generate free radicals from the attached platinum atom. Despite the uncertainty with carboplatin’s mechanism, it has shown to be highly effective antineoplastic compound when paired with paclitaxel (GoldBio Catalog # P-925) and bevacizumab.

Carfilzomib is a second generation proteasome inhibitor that has been used in oncology research.Being a derivative of epoxomicin, carfilzomib has a tetrapeptide epoxyketone structure.

The anti-cancer activity of carfilzomib on proteasomes is attributed to irreversibly binding to a 20S subunit on proteasomes. Affinity of carfilzomib for the subunit has been shown to be fairly significant, allowing carfilzomib to be effective at targeting multiple myeloma and lymphoma.

Proteasomes degrade excess or damaged proteins in both the nucleus and cytosol by cleaving hydrophobic residue peptide bonds. When proteasomes are inhibited by carfilzomib, polyubiquinated proteins accumulate. Polyubiquinated proteins will upregulate p21 synthesis, which activates cell cycle arrest and eventually apoptosis.

Carfilzomib has also been shown to have poor solubility in aqueous solutions, but greater solubility in organic solvents such as DMSO. Aqueous solubility can be enhanced by diluting carfilzomib-organic solvent solution in aqueous buffers. Using aqueous carfilzomib in biological settings should be done in dilute concentrations to limit organic solvent presence. Because carfilzomib organic-aqueous solutions only have a shelf life of approximately 24 hours, it is recommended to make small portions for immediate use.