acacetin and Neoplasms

Due to the promising features of the ancient herbal plant Artemisia, its biologic activity has been investigated for use in modern medicine. In this regard, Artemisia and its active phytochemicals have been introduced as having antimalarial, antioxidant, cytotoxic, antispasmodic, anthelmintic, neuroprotective, anti-inflammatory, and antimicrobial agents. In the case of cancer treatment, the plant species and its bioactive compounds target multiple pathways. Here we reviewed the scientific literature published up until 2018, which have explained the cytotoxic activity of the Artemisia species and their constituents. This review summarizes the published data found in PubMed, Science Direct and Scopus. Here, studies about the cytotoxicity and antitumor action on cancer cells and tumor bearing animals are discussed. Also, detailed molecular pathways affected by the plant and the phytochemistry of the cytotoxic active components are presented. Among all species and chemical constituents, the active ones have been selected and discussed in detail. The cytotoxic comparison made here may open a window for future works and selection of agents for cancer chemotherapy.

Topics: Animals; Antineoplastic Agents, Phytogenic; Artemisia; Cell Proliferation; Humans; Molecular Structure; Neoplasms; Neoplasms, Experimental; Plant Extracts; Plants, Medicinal

Acacetin is a di-hydroxy and mono-methoxy flavone present in various plants, including black locust, Damiana, Silver birch. Literature information revealed that acacetin exhibits an array of pharmacological potential including chemopreventive and cytotoxic properties in cancer cell lines, prevents ischemia/reperfusion/myocardial infarction-induced cardiac injury, lipopolysaccharide (LPS), 1-methyl-4-phenyl pyridinium ion (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced neuroinflammation, LPS and sepsis-induced lung injury, rheumatoid and collagen-induced arthritis, inhibit the microbial growth, obesity, viral-mediated infections as well as hepatic protection.. This review highlights the therapeutic potential of acacetin, with updated and comprehensive information on the biological sources, chemistry, and pharmacological properties along with the possible mechanism of action, safety aspects, and future research opportunities.. The information was retrieved from various search engines, including Pubmed, SciFinder, Science direct, Inxight:drugs, Google scholar, and Meta cyc.. The first section of this review focuses on the detailed biological source of acacetin, chromatographic techniques used for isolation, chemical characteristics, the method for the synthesis of acacetin, and the available natural and synthetic derivatives. Subsequently, the pharmacological activities, including anti-cancer, anti-inflammatory, anti-viral, anti-microbial, anti-obesity, have been discussed. The pharmacokinetics data and toxicity profile of acacetin are also discussed.. Acacetin is a potent molecule reported for its strong anti-inflammatory and anti-cancer activity, however further scientific evidence is essential to validate its potency in disease models associated with inflammation and cancer. There is limited information available for toxicity profiling of acacetin; therefore, further studies would aid in establishing this natural flavone as a potent candidate for research studies at clinical setup.

Topics: Animals; Anti-Inflammatory Agents; Antimetabolites; Antineoplastic Agents; Flavones; Humans; Inflammation; Metabolic Diseases; Neoplasms

Phytoestrogens are class of natural compounds that shares structural similarity with estrogen and has the capacity to alter the fertilization in mammals. Till early 1990s, the natural phytoestrogens as well as their synthetic analogues were explored for their fertility modulating activity. During late 1990s, two findings renewed the interest on phytoestrogens as means to control hormone induced cancer: (i) revelation of overexpression of CYP1B1 in breast & ovarian cancer and (ii) protection offered by alphanapthoflavone (ANF) against hormone induced cancer. The objective of the review is to summarize the CYP1B1 inhibitory activity of phytoestrogens and their synthetic analogues reported till date. This review is an attempt to classify phytoestrogens and their synthetic analogues on their chemical architecture rather than simply by their chemical class (flavones, stilbenes etc.). This provides a broader sense to cluster many chemical classes under a particular chemical architecture/framework. Accordingly, we divided the phytoestrogen into three different classes based on two aryl groups (Ar) separated by linker (X), which may be either cyclic (c) or linear (l). The number in subscript to X denotes number of atoms: (i) Ar-cX

Topics: Animals; Antineoplastic Agents, Phytogenic; Classification; Cluster Analysis; Cytochrome P-450 CYP1B1; Enzyme Inhibitors; Humans; Molecular Mimicry; Neoplasms; Phytoestrogens

Cytochrome P450s (CYPs) represent a large class of heme-containing enzymes that catalyze the metabolism of multitudes of substrates both endogenous and exogenous. Until recently, however, CYPs have been largely overlooked in cancer drug development, acknowledged only for their role in phase I metabolism of chemotherapeutics. The first successful strategy targeting CYP enzymes in cancer therapy was the development of potent inhibitors of CYP19 (aromatase) for the treatment of breast cancer. Aromatase inhibitors ushered in a new era in hormone ablation therapy for estrogen dependent cancers, and have paved the way for similar strategies (i.e., inhibition of CYP17) that combat androgen dependent prostate cancer. Identification of CYPs involved in the inactivation of anti-cancer metabolites of vitamin D(3) and vitamin A has triggered development of agents that target these enzymes as well. The discovery of the over-expression of exogenous metabolizing CYPs, such as CYP1B1, in cancer cells has roused interest in the development of inhibitors for chemoprevention and of prodrugs designed to be activated by CYPs only in cancer cells. Finally, the expression of CYPs within tumors has been utilized in the development of bioreductive molecules that are activated by CYPs only under hypoxic conditions. This review offers the first comprehensive analysis of strategies in drug development that either inhibit or exploit CYP enzymes for the treatment of cancer.

Topics: Antineoplastic Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Neoplasms

Protein kinases associated with cancer genes play vital role in angiogenesis, invasion, motility, proliferation, and survival. Therefore, cancer prevention/treatment, targeting kinases with phytochemicals could be a promising approach. Given potential of phytochemicals in modulating cancer-associated kinases, present study aims to find inhibitory prospects of selected flavonoids for cancer-chemoprevention/treatment. The molecular docking interaction analysis was done by exploring binding potential of flavonoids with kinases (PI3K, Akt, mTOR, EGFR, MAPK, MKK4, Fyn, ZAP-70, B-Raf, JAK-2, STAT-1, STAT-3, STAT-4, STAT-5, and VEGF) involved in various carcinogenesis phases. Among flavonoids acacetin showed highest binding-energy against JAK-2 following Fyn > VEGF > PI3K > MKK4 > MAPK > BRaf > STAT-5 > STAT-1 > STAT-4 whereas pinostrobin depicts higher binding-energy with JAK-2 followed by B-Raf > MKK4 > VEGF > PI3K > MAPK > STAT-1 > STAT-4 > STAT-5. Further, molecular-dynamic simulation revealed that pinostrobin interacted with JAK-2 protein with binding-energy of -25.068 ± 1.08 kJ/mol whereas acacetin interacted with both JAK-2 and Fyn with binding-energies of -23.466 ± 0.9508 kJ/mol and-8.935 ± 1.3108 kJ/mol respectively. High binding-energy, low inhibition-constant, and drug-likeness of acacetin and pinostrobin provide a clue for their usage as a JAK-2 inhibitor which could be useful for molecular/cell-target based in-vitro and in-vivo investigations.

Topics: Adaptor Proteins, Signal Transducing; Cytochrome P-450 CYP2D6; Disaccharides; Flavanones; Flavones; Flavonoids; Humans; Hydrogen Bonding; Molecular Docking Simulation; Molecular Dynamics Simulation; Neoplasms; Protein Kinases; Thermodynamics