nsc-4347 and Neoplasms

Cancer has become the primary cause of death worldwide, and anticancer drugs are used to combat this disease. Synthesis of anticancer drugs has limited success due to adverse side effects has made compounds from natural products with minimal toxicity gain much popularity. Piper species are known to have a biological effect on human health. The biological activity is due to Piper species rich with active secondary metabolites that can combat most diseases, including cancer. This review will discuss the phytochemistry of Piper species and their anticancer activity. The identification and characterization of ten active metabolites isolated from Piper species were discussed in detail and their anticancer mechanism. These metabolites were mainly found could inhibit anticancer through caspase and P38/JNK pathways. The findings discussed in this review support the therapeutic potential of Piper species against cancer due to their rich source of active metabolites with demonstrated anticancer activity.

Topics: Antineoplastic Agents; Caspases; Humans; Neoplasms; Piper; Plant Extracts

Recently many studies showed anticancer activities of piperine, a pungent alkaloid found in black pepper and some other Piper species. We attempted to summarize acquired data that support anticancer potential of this natural agent. Piperine has been reported to possess effective chemopreventive activity. It has been studied to affect via several mechanisms of action, in brief enhancing antioxidant system, increasing level and activity of detoxifying enzymes and suppressing stem cell self-renewal. Moreover, piperine has been found to inhibit proliferation and survival of various cancerous cell lines via modulating cell cycle progression and exhibiting anti-apoptotic activity, respectively. This compound has been shown to modify activity of various enzymes and transcription factors to inhibit invasion, metastasis and angiogenesis. Interestingly, piperine has exhibited antimutagenic activity and also inhibited activity and expression of multidrug resistance transporters such as P-gp and MRP-1. Besides, about all reviewed studies have reported selective cytotoxic activity of piperine on cancerous cells in compared with normal cells. Altogether, the studies completely underline promising candidacy of piperine for further development. The collected preclinical data we provided in this article can be useful in the design of future researches especially clinical trials with piperine.

Topics: Alkaloids; Animals; Anticarcinogenic Agents; Antimutagenic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Benzodioxoles; Biological Availability; Cell Proliferation; Cell Survival; Drug Evaluation, Preclinical; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Inactivation, Metabolic; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Piper; Piperidines; Polyunsaturated Alkamides; Stem Cells

Piperlongumine, also known as piplartine, is an amide alkaloid of Piper longum L. (long piper), a medical plant known from Ayurvedic medicine. Although was discovered well over fifty years ago, its pharmacological properties have been uncovered in the past decade. In particular, piperlongumine has been most extensively studied as a potential anticancer agent. Piperlongumine has exhibited cytotoxicity against a broad spectrum of human cancer cell lines, as well as demonstrated antitumor activity in rodents. Piperlongumine has also been found to be a proapoptotic, anti-invasive, antiangiogenic agent and synergize with modern chemotherapeutic agents. Because of its clinical potential, several studies were undertaken to obtain piperlongumine analogues, which have exhibited more potent activity or more appropriate drug-like parameters. In this review, the synthesis of piperlongumine analogues and piperlongumine-based hybrid compounds, as well as their anticancer properties and the molecular basis for their activity are explored. General structure-activity relationship conclusions are drawn and directions for the future research are indicated.

Topics: Animals; Antineoplastic Agents, Phytogenic; Chemistry Techniques, Synthetic; Dioxolanes; Drug Discovery; Humans; Neoplasms; Piper; Piperidones; Structure-Activity Relationship

The oxidative pentose phosphate pathway (PPP) contributes to tumour growth, but the precise contribution of 6-phosphogluconate dehydrogenase (6PGD), the third enzyme in this pathway, to tumorigenesis remains unclear. We found that suppression of 6PGD decreased lipogenesis and RNA biosynthesis and elevated ROS levels in cancer cells, attenuating cell proliferation and tumour growth. 6PGD-mediated production of ribulose-5-phosphate (Ru-5-P) inhibits AMPK activation by disrupting the active LKB1 complex, thereby activating acetyl-CoA carboxylase 1 and lipogenesis. Ru-5-P and NADPH are thought to be precursors in RNA biosynthesis and lipogenesis, respectively; thus, our findings provide an additional link between the oxidative PPP and lipogenesis through Ru-5-P-dependent inhibition of LKB1-AMPK signalling. Moreover, we identified and developed 6PGD inhibitors, physcion and its derivative S3, that effectively inhibited 6PGD, cancer cell proliferation and tumour growth in nude mice xenografts without obvious toxicity, suggesting that 6PGD could be an anticancer target.

Topics: AMP-Activated Protein Kinase Kinases; AMP-Activated Protein Kinases; Humans; Lipogenesis; Neoplasms; Oxidative Stress; Pentose Phosphate Pathway; Phosphogluconate Dehydrogenase; Protein Serine-Threonine Kinases; Ribulosephosphates; Signal Transduction

Piplartine (piperlongumine, 5,6-dihydro-1-[(2E)-1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-2(1H)-pyridinone) is a biologically active alkaloid/amide from peppers, as from long pepper (Piper longum L. - Piperaceae). Long pepper is one of the most widely used in Ayurvedic medicine, which is used to treat many diseases, including tumors. The purpose of the current paper is to address to the chemical structure establishment and to systematically survey the published articles and highlight recent advances in the knowledge of the therapeutic potential of piplartine, establishing new goals for future research. The reported pharmacological activities of piplartine include cytotoxic, genotoxic, antitumor, antiangiogenic, antimetastatic, antiplatelet aggregation, antinociceptive, anxiolytic, antidepressant, anti-atherosclerotic, antidiabetic, antibacterial, antifungal, leishmanicidal, trypanocidal, and schistosomicidal activities. Among the multiple pharmacological effects of piplartine, its anticancer property is the most promising. Therefore, the preclinical anticancer potential of piplartine has been extensively investigated, which recently resulted in one patent. This compound is selectively cytotoxic against cancer cells by induction of oxidative stress, induces genotoxicity, as an alternative strategy to killing tumor cells, has excellent oral bioavailability in mice, inhibits tumor growth in mice, and presents only weak systemic toxicity. In summary, we conclude that piplartine is effective for use in cancer therapy and its safety using chronic toxicological studies should be addressed to support the viability of clinical trials.

Topics: Animals; Antineoplastic Agents, Phytogenic; Biological Availability; Drugs, Investigational; Fruit; Humans; Medicine, Ayurvedic; Neoplasms; Patents as Topic; Piper; Piperidones

Piper has been used for long timelike condiment and food, but also in traditional medicine around of the world. This work resumes the available and up to date work done on members of the Piperaceae family and their uses for therapeutic purposes.. Information on Piper genus was gathered via internet using scientific databases such as Scirus, Google Scholar, CAB-abstracts, MedlinePlus, Pubmed, SciFinder, Scopus and Web of Science.. The largeleafed perennial plant Piper is used for its spicy aromatic scent and flavor. It has an important presence in the cuisine of different cultures. Another quality of these plants is their known medicinal properties. It has been used as emollient, antirheumatic, diuretic, stimulant, abortifacient, anti-inflammatory, antibacterial, antifungal and antidermatophytic. A survey of the literature shows that the genus Piper is mainly known for its alkaloids with cytotoxic, chemopreventive, antimetastatic and antitumor properties in several types of cancer. Studies of its alkaloids highlight the existence of various potential leads to develop new anti-cancer agents. Modern pharmacology studies have demonstrated that its crude extracts and active compounds possess wide pharmacological activities, especially asantioxidant, anti-depressive, hepatoprotective, antimicrobial, anti-obesity, neuropharmacological, to treat cognitive disorders, anti-hyperlipidemic, anti-feedant, cardioactive, immuno-enhancing, and anti-inflamatory. All this evidence supporting its traditional uses.. This review summarizes the up-to-date and comprehensive information concerning the botany, traditional use, phytochemistry and pharmacology of Piper together with its toxicology, and discusses the possible trend and scope for further research on Piper in the future.

Topics: Alkaloids; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-Obesity Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Cardiovascular Agents; Cardiovascular Diseases; Central Nervous System Agents; Cognition Disorders; Humans; Neoplasms; Obesity; Piper; Plant Extracts; Platelet Aggregation Inhibitors

Topics: Adult; Aged; Aged, 80 and over; Air Pollutants; Air Pollution; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Antigens, Surface; Antineoplastic Agents; Antioxidants; Antiviral Agents; Aporphines; Atherosclerosis; Benzoyl Peroxide; beta Catenin; Biofilms; Biomarkers; Brain; Cannabis; Carcinoma, Squamous Cell; Case-Control Studies; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Child; China; Chlorides; Chlorophyll; Cholesterol, LDL; Coinfection; Corylus; Cross-Sectional Studies; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Developmental Disabilities; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Screening Assays, Antitumor; Electroencephalography; Environmental Exposure; Enzyme Inhibitors; Epilepsy, Generalized; Ethnicity; Female; Fertilization in Vitro; Fluorescent Dyes; Follow-Up Studies; Forecasting; Glutamate Carboxypeptidase II; Glycine; Half-Life; Head and Neck Neoplasms; Health Communication; Heart Ventricles; Hepacivirus; Hepatitis C; Heterosexuality; HIV Infections; Humans; Hypercholesterolemia; Immunoassay; Inhalation Exposure; Isocitrate Dehydrogenase; Laryngeal Neoplasms; Ligands; Light; Lipopolysaccharide Receptors; Liver Cirrhosis; Lung; Lung Neoplasms; Magnetic Resonance Imaging, Cine; Male; Maternal Age; Mechanical Phenomena; Mice; Mice, Nude; Mice, SCID; Microglia; MicroRNAs; Microscopy, Fluorescence; Microsomes, Liver; Middle Aged; Minority Groups; Mitochondrial Membrane Transport Proteins; Models, Biological; Molecular Structure; Molecular Weight; Monte Carlo Method; Muscle Hypotonia; Mutagenesis, Site-Directed; Mutation, Missense; Natriuretic Peptide, Brain; Neoplasms; Nickel; Nitric Oxide; Optical Imaging; Oxides; Particle Size; Particulate Matter; PCSK9 Inhibitors; Peptide Fragments; Phenotype; Photochemotherapy; Photosensitizing Agents; Phytochemicals; Piper; Placenta Growth Factor; Plant Extracts; Plant Leaves; Plant Stems; Platinum; Point-of-Care Testing; Population Surveillance; Postpartum Period; Pregnancy; Pregnancy, Twin; Prevalence; Prospective Studies; Prostatic Neoplasms; Pseudomonas aeruginosa; Pyridines; Pyridones; Racial Groups; Rats; Respiratory Physiological Phenomena; Retrospective Studies; Risk Factors; RNA, Long Noncoding; Semiconductors; Sexual and Gender Minorities; Sexual Behavior; Social Media; Sodium; Solubility; Stereoisomerism; Stochastic Processes; Structure-Activity Relationship; Substance-Related Disorders; Sustained Virologic Response; Sweat; Temperature; Time Factors; Tissue Distribution; Titanium; Transplantation, Heterologous; Tumor Cells, Cultured; Tungsten; Tyramine; United States; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Function, Left; Veterans; Xenograft Model Antitumor Assays; Young Adult

Chronic inflammation provides a favorable microenvironment for tumorigenesis, which opens opportunities for targeting cancer development and progression. Piplartine (PL) is a biologically active alkaloid from long peppers that exhibits anti-inflammatory and antitumor activity. In the present study, we investigated the physical and chemical interactions of PL with anti-inflammatory compounds and their effects on cell proliferation and migration and on the gene expression of inflammatory mediators. Molecular docking data and physicochemical analysis suggested that PL shows potential interactions with a peptide of annexin A1 (ANXA1), an endogenous anti-inflammatory mediator with therapeutic potential in cancer. Treatment of neoplastic cells with PL alone or with annexin A1 mimic peptide reduced cell proliferation and viability and modulated the expression of MCP-1 chemokine, IL-8 cytokine and genes involved in inflammatory processes. The results also suggested an inhibitory effect of PL on tubulin expression. In addition, PL apparently had no influence on cell migration and invasion at the concentration tested. Considering the role of inflammation in the context of promoting tumor initiation, the present study shows the potential of piplartine as a therapeutic immunomodulator for cancer prevention and progression.

Topics: Alkaloids; Annexin A1; Anti-Inflammatory Agents; Antineoplastic Agents; Carcinogenesis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chemokine CCL2; Gene Expression Regulation, Neoplastic; Humans; Inflammation; Neoplasm Invasiveness; Neoplasms; Piper; Piperidones; Tumor Microenvironment

(-)-Cubebin, isolated from the seeds of Piper cubeba, and its five different types of derivatives (a total of 17), with varying functionalities, were tested for their in vitro anticancer activity against six human cancer cell lines (A549, K562, SiHa, KB, HCT116 and HT29) using MTT assay. Cubebin as well as its derivatives containing lactone and amide groups showed significant anticancer activity. In some of the tested cell lines, the amide derivatives showed higher activity. Morphological analysis indicated that these compounds act through apoptosis mediated pathway of cell death and we expect that these results will pave new paths in the development of novel anticancer agents by the derivatization of (-)-cubebin.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Humans; Lignans; Models, Molecular; Neoplasms; Piper; Seeds

To assess the benefits of regular exercise in reducing harms associated with betel quid (BQ) chewing.. The study cohort, 419,378 individuals, participated in a medical screening program between 1994 and 2008, with 38,324 male and 1,495 female chewers, who consumed 5-15 quids of BQ a day. Physical activity of each individual, based on "MET-hour/week", was classified as "inactive" or "active", where activity started from a daily 15 minutes/day or more of brisk walking (≥3.75 MET-hour/week). Hazard ratios for mortality and remaining years in life expectancy were calculated.. Nearly one fifth (18.7%) of men, but only 0.7% of women were chewers. Chewers had a 10-fold increase in oral cancer risk; and a 2-3-fold increase in mortality from lung, esophagus and liver cancer, cardiovascular disease, and diabetes, with doubling of all-cause mortality. More than half of chewers were physically inactive (59%). Physical activity was beneficial for chewers, with a reduction of all-cause mortality by 19%. Inactive chewers had their lifespan shortened by 6.3 years, compared to non-chewers, but being active, chewers improved their health by gaining 2.5 years. The improvement, however, fell short of offsetting the harms from chewing.. Chewers had serious health consequences, but being physically active, chewers could mitigate some of these adverse effects, and extend life expectancy by 2.5 years and reduce mortality by one fifth. Encouraging exercise, in addition to quitting chewing, remains the best advice for 1.5 million chewers in Taiwan.

Topics: Adult; Areca; Diabetes Mellitus; Female; Humans; Male; Mastication; Middle Aged; Motor Activity; Neoplasms; Piper; Prospective Studies; Risk-Taking; Taiwan

Currently chemotherapy is limited mostly to genotoxic drugs that are associated with severe side effects due to non-selective targeting of normal tissue. Natural products play a significant role in the development of most chemotherapeutic agents, with 74.8% of all available chemotherapy being derived from natural products.. To scientifically assess and validate the anticancer potential of an ethanolic extract of the fruit of the Long pepper (PLX), a plant of the piperaceae family that has been used in traditional medicine, especially Ayurveda and investigate the anticancer mechanism of action of PLX against cancer cells.. Following treatment with ethanolic long pepper extract, cell viability was assessed using a water-soluble tetrazolium salt; apoptosis induction was observed following nuclear staining by Hoechst, binding of annexin V to the externalized phosphatidyl serine and phase contrast microscopy. Image-based cytometry was used to detect the effect of long pepper extract on the production of reactive oxygen species and the dissipation of the mitochondrial membrane potential following Tetramethylrhodamine or 5,5,6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine chloride staining (JC-1). Assessment of PLX in-vivo was carried out using Balb/C mice (toxicity) and CD-1 nu/nu immunocompromised mice (efficacy). HPLC analysis enabled detection of some primary compounds present within our long pepper extract.. Our results indicated that an ethanolic long pepper extract selectively induces caspase-independent apoptosis in cancer cells, without affecting non-cancerous cells, by targeting the mitochondria, leading to dissipation of the mitochondrial membrane potential and increase in ROS production. Release of the AIF and endonuclease G from isolated mitochondria confirms the mitochondria as a potential target of long pepper. The efficacy of PLX in in-vivo studies indicates that oral administration is able to halt the growth of colon cancer tumors in immunocompromised mice, with no associated toxicity. These results demonstrate the potentially safe and non-toxic alternative that is long pepper extract for cancer therapy.

Topics: Animals; Apoptosis; Blotting, Western; Cell Cycle; Cell Proliferation; Humans; Immunoenzyme Techniques; In Vitro Techniques; Male; Membrane Potential, Mitochondrial; Mice; Mice, Inbred BALB C; Mice, Nude; Mitochondria; Neoplasms; Piper; Plant Extracts; Reactive Oxygen Species; Tumor Cells, Cultured; Xenograft Model Antitumor Assays