Anti-Cancer

Flubendazole is a benzimidazole compound that is used as an antiparasitic and anti-cancer agent. It has been shown to be an effective anthelminthic chemical by inhibiting tubulin synthesis and disrupting cytoskeleton formation. Flubendazole has also been shown in vivo to be a strong anti-cancer compound by the same mechanism and is potent toward vinblastine resistant cell lines.

Tubulin is vital protein component that provides the structural shape of cells as well as being integral to replication. Halting tubulin formation ruins the structural integrity and dysregulates cytosolic equilibrium. Tubulin inhibition also effects the subfamilies α-tubulin and β-tubulin which facilitate chromosomal migration during cellular replication.

Formononetin is an isoflavonoid phytoestrogen that is used in microbiology and oncology research as a vasodilator, anti-viral, anti-inflammatory and anti-cancer agent. It has also been used as an anti-parasitic compound against Giardia lamblia trophozoites however, the mechanism of action is not well understood.

Gefitinib is an anti-cancer agent similar to erlotinib. It functions through inhibiting the overexpressed or mutated epidermal growth factor receptor (EGFR) by binding its ATP binding site. Overexpression and mutation of EGFR are common in cancer cell lines and may lead to uncontrolled proliferation through the Ras signaling cascade. Gefitinib has been shown to induce tumor cell apoptosis in HaCaT cells, KG-1 cells, P39 cells, and CD34+ myeloblasts. Additionally, it has been shown to promote keratinocyte apoptosis.

Germacrone is an essential oil extracted from Rhizoma curcuma and has been used as an anti-cancer and anti-viral agent. It has been shown to eliminate hepatic and breast cancer cell lines by inhibiting cyclin dependent kinase 2 (CDK2) activity. It has also been shown to upregulate apoptotic protein expression.

Inhibition of viral replication by germacrone occurs early in the virus cycle. When used against influenza, germacrone inhibited in vivo and in vitro viral replication by inhibiting viral RNA and protein synthesis. This prevents viral replication after splicing DNA by removing the needed materials for proliferation.

Hydroxyurea is a compound used in anti-cancer research to inhibit DNA synthesis and in sickle cell research for ways to alleviate symptoms. It has been shown to be a potent inhibitor of ribonucleotide reductase which reduces ribonucleotides to deoxyribonucleotides.

In vivo research has shown hydroxyurea converting into a free radical nitric oxide which binds the active site of ribonucleotide reductase, ceasing further DNA synthesis. The mechanism of nitric oxide release from hydroxyurea is not well understood.

Hydroxyurea has also been shown to alleviate sickle cell anemia through its conversion to nitric oxide in vivo. Nitric oxide alleviates endogenous nitric oxide loss, caused by hemolysis, and stimulates soluble guanylate cyclase (sGC) activity which will signal fetal hemoglobin production.

Icariin is a prenylflavonoid with anti-cancer properties and is studied for its diverse signaling effects observed in vivo. It has been documented to stimulate pathways that induce osteogenesis, decrease inflammation and promote angiogenesis.

Icariin has been shown in vivo to induce mice bone formation through upregulating runt-related transcription factor 2 (Runx2) genes and increasing bone morphogenic protein expression. These prompt osteogenic differentiation and bone development. Also, icariin invokes marrow stromal cell proliferation via increased alkaline phosphatase activity.

In vitro, icariin has been used to induce apoptosis by generating reactive oxygen species (ROS) and stimulating c-Jun N-terminal kinase (JNK) activity. Both of these apoptosis inducing processes compromise mitochondrial membranes to release cytochrome c. The generation of ROS causes direct damage to the membrane while JNK prompts downstream molecules to form pores in mitochondrial membranes.

Icariin has also been shown to inhibit nuclear factor-κB (NF-κB) expression, decreasing cytokine production. Additionally, icariin innervates phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) cell cycle pathways. The PI3K/AKT pathway has been demonstrated in vitro to induce angiogenesis, following the addition of icariin.

Icaritin is a prenylflavonoid derivative of icariin (Goldbio # I-215) and has been used for oncology research, to influence bone formation and displays neuroprotective effects. Applications in oncology and neurology research have been related to the activity of icaritin on estrogen receptors.

Within the field of cancer research, icaritin has been shown to act as an agonist and antagonist on estrogen receptors in vivo which was based upon concentration in different cancer lines. Icaritin was shown in vitro to sustain extracellular signal–regulated kinase (ERK) activity through stimulating estrogen receptors. Prolonged ERK activation arrested the cell cycle in the G2 stage and subsequently triggered apoptosis. Anti-cancer activity of icaritin has also been observed to occur in estrogen receptor negative cancer cells, showing an estrogen receptor independent pathway.

For Alzheimer’s research, icaritin has been investigated for attenuating cytotoxic effects caused by β-Amyloid proteins. While the mechanism for neuroprotection has not been elucidated, icaritin was shown to possibly exert these effects through mitogen-protein kinase (MAPK)/ERK cell signaling pathways.

Icaritin exerts an osteogenic effect in vivo by forming a bioactive scaffold that promotes bone growth while also increasing alkaline phosphatase (ALP) activity. It is also used to inhibit osteoclast differentiation and activity through suppression of receptor activator of nuclear factor kappa-B ligand (RANKL).

Icotinib hydrochloride or icotinib HCl, is a first generation inhibitor of tyrosine kinase epidermal growth factor receptor (EGFR-TK). It has been used in measuring the efficacy of novel anti-cancer compounds in vivo against non-small-cell lung cancers that formed advanced solid tumors. Icotinib reversibly inhibits EGFR-TK competitively by blocking the ATP-binding site on tyrosine kinase.

Ingenol mebutate (Ingenol-3-mebutate) is a hydrophobic diterpene ester extracted from the plant Euphorbia peplus. This compound is used in oncology research as an activator of the protein kinase C (PKC) family. Ingenol mebutate has been effective against basal cell carcinomas, squamous cell carcinomas and actinic keratosis.

Research on stimulation of PKC pathways by ingenol mebutate were shown to promote apoptosis, arrest cell growth and increase neutrophilic infiltration. Halting cell growth subsequently leads to apoptosis due to intracellular signals triggered from a lack of progression in the cell cycle. Ingenol mebutate diminished relapse rates of mice tumors in vivo and in vitro by inducing neutrophil recruiting and activating pathways. These pathways include releasing inflammatory cytokines interleukin 8 (IL8), interleukin 1 (IL1) as well as tumor necrosis factor alpha (TNF-α) which attract neutrophils to the inflammatory site.

Isoxanthohumol is a prenylflavonoid compound extracted from Humulus lupulus L., the common hop plant. It has displayed strong estrogenic effects and has been used for anti-cancer research. Isoxanthohumol has also been shown to form the potent phytoestrogen 8-prenylnaringenin (8PN), which forms by cleaving off an ether group.

Oncology research on Isoxanthohumol activity has shown a significant degree of efficacy against breast, prostate and colon cancer cell lines. It has also been to shown to attenuate transforming growth factor-β (TGF-1 β) expression and disrupt Janus kinase/ signal transducer and activator of transcription (JAK/STAT) pathways which activate oncogenic genes.

Ixazomib citrate is a citrate salt that is a second generation proteasome inhibitor used for anti-cancer research. In vivo research has shown ixazomib citrate to hydrolyze into its active ixazomib form which reversibly inhibits 20S proteasomes in multiple myeloma cancer cells. Ceasing this enzyme’s activity has been shown to decrease angiogenesis, induce apoptotic pathways and upregulate tumor suppressor genes.

Methotrexate sodium salt is an anti-cancer agent that works by inhibiting folic acid metabolism. Methotrexate is an allosteric dihydrofolate reductase (DHFR) inhibitor. DHFR is is an essential enzyme in folic acid metabolism. Folic acid is necessary for production of thymidine and purine; therefore, methotrexate is a nucleic acid synthesis inhibitor. It is freely soluble in aqueous solution.

Mitomycin C is an antineoplastic antibiotic isolated from Streptomyces caespitosus. It is effective against gram-negative and gram-positive bacteria and a variety of cancer cells, including Ehrlich ascites tumor cells. Mitomycin C has been used to produce mitotically inactivated feeder cells and has been shown to increase recombination during fruit fly meiosis. It is capable of killing mutant strains of Arabidopsis that are defective for recombination during meiosis.

Mitomycin C functions as a DNA crosslinking agent, inhibiting DNA synthesis.

Mitoxantrone HCl is an anthracenedione anti-cancer agent. It functions by intercalating between DNA and causing double-stranded breaks. This inhibits T-cell, B-cell, and macrophage division and prevents DNA repair and synthesis. It has been shown to be effective against breast cancers, leukemias, and non-Hodgkin’s lymphoma. It also exhibits immunosuppressive activity by inducing apoptosis in antigen-presenting T-cells and is an immune system regulator in multiple sclerosis.

Nicotinamide is a metabolized amide form of vitamin B3. It is an anti-cancer agent and inhibitor of PARP-1, which is responsible for repairing DNA damage caused by chemotherapy. Nicotinamide is converted to nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) for use in biological redox reactions. Additionally, nicotinamide is a nicotinamide phosphoribosyltransferase (NAMPT) substrate and anti-inflammatory agent.

Paclitaxel is an anti-cancer taxane drug. It stabilizes microtubules arresting the cell cycle. This induces apoptosis through a JNK-dependent and JNK-independent pathway. It is used as a component of dechlorination buffer and as an internal standard for chromatographic docetaxel studies.

Rapamycin is a macrolide antibiotic isolated from Streptomyces hygroscopicus. It has been shown to display anticancer activity such as induction of apoptosis and inhibition of angiogenesis and proliferation in tumor cell lines. Rapamycin is also an immunosuppressant and FRAP inhibitor and inhibits lymphokine-induced cell proliferation.

Streptozocin is an anti-tumor agent reserved as a last resort against metastatic pancreatic islet cells. Streptozocin functions by adding methyl and alkyl groups to DNA and interfering with normal base pairing. This damages the DNA and causes a decrease in tumor size. Streptozocin enters cells via the glucose transport protein, GLUT2. It is capable of causing vasorelaxation, NCOAT inhibition, and donating nitric oxide (NO).

Tamoxifen citrate is an anti-cancer agent and protein kinase C inhibitor. It has been shown to induce apoptosis in human malignant glioma cells and to block VEGF production in breast cancer cells. Additionally, tamoxifen’s effects on radiation sensitivity have been studied. It has been used to analyze steroid receptors on human breast cancer cells and to study triacylglycerol accumulation in the liver. Tamoxifen is an estrogen receptor activator.

Thiostrepton is a cyclic peptide antibiotic isolated from Streptomyces azureus. It targets a wide variety of gram-negative and gram-positive bacteria, especially those causing skin infections. It has been used as a marker for selection of recombinant Streptomyces cultures. Additionally, thiostrepton has been shown to inhibit FOXM1, a gene commonly overexpressed in cancer cell lines, thus inhibiting cancer cell growth.

Thiostrepton functions by binding elongation factor G (EF-G) and interfering with ribosomal GTPase activity, ultimately inhibiting protein synthesis.