piperine and Lung-Neoplasms

G-quadruplex (G4) structures are considered a promising therapeutic target in cancer. Since Ayurveda, Piperine has been known for its medicinal properties. Piperine shows anticancer properties by stabilizing the G4 motif present upstream of the c-myc gene. This gene belongs to a group of proto-oncogenes, and its aberrant transcription drives tumorigenesis. The transcriptional regulation of the c-myc gene is an interesting approach for anticancer drug design. The present study employed a chemical similarity approach to identify Piperine similar compounds and analyzed their interaction with cancer-associated G-quadruplex motifs. Among all Piperine analogs, PIP-2 exhibited strong selectivity, specificity, and affinity towards c-myc G4 DNA as elaborated through biophysical studies such as fluorescence emission, isothermal calorimetry, and circular dichroism. Moreover, our biophysical observations are supported by molecular dynamics analysis and cellular-based studies. Our study showed that PIP-2 showed higher toxicity against the A549 lung cancer cell line but lower toxicity towards normal HEK 293 cells, indicating increased efficacy of the drug at the cellular level. Biological evaluation assays such as TFP reporter assay, quantitative real-time PCR (qRT- PCR), and western blotting suggest that the Piperine analog-2 (PIP-2) stabilizes the G-quadruplex motif located at the promoter site of c-myc oncogene and downregulates its expression. In conclusion, Piperine analog PIP-2 may be used as anticancer therapeutics as it affects the c-myc oncogene expression via G-quadruplex mediated mechanism.

Topics: A549 Cells; Alkaloids; Antineoplastic Agents; Apoptosis; Benzodioxoles; Down-Regulation; G-Quadruplexes; Gene Expression Regulation, Neoplastic; HEK293 Cells; HeLa Cells; Humans; Lung Neoplasms; MCF-7 Cells; Molecular Dynamics Simulation; Molecular Structure; Molecular Targeted Therapy; Piperidines; Polyunsaturated Alkamides; Promoter Regions, Genetic; Proto-Oncogene Proteins c-myc; Structure-Activity Relationship; Transcription, Genetic

Benjakul, a Thai traditional herbal preparation, comnprises five plants: Piper chaba, Piper sarmentosum, Piper interruptum, Plumbago indica, and Zingiber officinale. It has widely been used to treat cancer patients in folk medicine in Thailand. Benjakul extract, and its isolated compounds should be investigated for cytotoxic activity and analysis isolated compounds from chemical fingerprinting.. To study cytotoxicity ofBenjakul extract and its isolatedpure compounds against human small cell lung cancer cell line (NCI-HI 688) and in normal human lungfibroblast cell line (MRC-5) and analysis the content ofisolated compounds for quality control of Benjakul extract.. Bioassay-guided fractionation was used for isolated active compounds from ethanolic extract of Benjakul. Cytotoxic activity was carried using the SRB assay. HPLC method was applied to analyze six isolated compound contentfrom Benjakul extract.. The ethanolic extract ofBenjakul showed cytotoxicity against NCI-H1688 with IC50 value = 36.15±4.35 μg/ml. Hexane fraction as semi-separation by VLC showed the best cytotoxic activity (21.1 7±7.42 μg/ml). Six isolated compounds were identified as myristicin, plumbagin, methyl piperate, 6-shogaol, 6-gingerol and piperine. Plumbagin exhibited the highest cytotoxic activity and 6-shogaol was the second most effective cytotoxic constituent (IC50 values = 1.41±0.01 and 6.45±0.19 μg/ml, respectively). Piperine showed the highest content in both ofHPLC analysis and column chromatography separation.. Benjakul extract exhibited cytotoxicity against NCI-HI 688. Plumbagin and 6-shogaol are bioactive markers for cytotoxicity against this small cell lung cancer cell line. Chromatographic fingerprinting can be used to analyze six cytotoxic compounds isolatedfrom the ethanolic extract ofBenjakul.

Topics: Alkaloids; Benzodioxoles; Catechols; Cell Line, Tumor; Chromatography, High Pressure Liquid; Drug Screening Assays, Antitumor; Ethanol; Fatty Alcohols; Humans; Lung Neoplasms; Medicine, Traditional; Naphthoquinones; Piper; Piperidines; Plant Extracts; Plumbaginaceae; Polyunsaturated Alkamides; Small Cell Lung Carcinoma; Thailand; Zingiber officinale

Benjakul [BEN], a Thai Traditional medicine preparation, is composed of five plants: Piper chaba fruit [PC], Piper sarmentosum root [PS], Piper interruptum stem [PI], Plumbago indica root [PL] and Zingiber officinale rhizome [ZO]. From selective interviews of folk doctors in Southern Thailand, it was found that Benjakul has been used for cancer patients.. To investigate cytotoxicity activity of Benjakul preparation [BEN] and its ingredients against three human cancer cell lines, large lung carcinoma cell line (COR-L23), cervical cancer cell line (Hela) liver cancer cell line (HepG2) as compared with normal lungfibroblast cell (MRC-5) by using SRB assay.. The extraction as imitated the method used by folk doctors was done by maceration in ethanol and boiling in water Bioassay guided isolation was used isolated cytotoxic compound.. The ethanolic extracts of PL, ZO, PC, PS, BEN and PS showed specific activity against lung cancer cell (IC50 = 3.4, 7.9, 15.8, 18.4, 19.8 and 32.91 microg/ml) but all the water extracts had no cytotoxic activity. Three active ingredients [6-gingerol, plumbagin and piperine as 0.54, 4.18 and 7.48% w/w yield of crude extract respectively] were isolated from the ethanolic extract of BEN and they also showed cytotoxic activity with plumbagin showing the highest cytotoxic activity against COR-L23, HepG2, Hela and MRC-5 (IC50 = 2.55, 2.61, 4.16 and 11.54 microM respectively).. These data results may support the Thai traditional doctors who are using Benjakul to treat cancer patients and three of its constituents (6-gingerol, plumbagin and piperine) are suggested to be used as biomarkers for standardization of this preparation.

Topics: Alkaloids; Benzodioxoles; Catechols; Cell Line, Tumor; Fatty Alcohols; Female; Humans; Liver Neoplasms; Lung Neoplasms; Medicine, East Asian Traditional; Naphthoquinones; Phytotherapy; Piper; Piperidines; Plant Extracts; Plants, Medicinal; Plumbaginaceae; Polyunsaturated Alkamides; Thailand; Uterine Cervical Neoplasms; Zingiber officinale

In recent years, considerable emphasis has been focused on identifying new cancer chemopreventive agents, which could be useful for the human population. Piperine is a pure, pungent alkaloid constituent of black and long peppers (Piper nigrum and Piper longum), that acts as an antioxidant and anticancer agent by its numerous macromolecules associated with them. In the present study, piperine was found to suppress benzo(a)pyrene (B(a)p) induced lung cancer in Swiss albino mice. In lung cancer bearing mice, altered levels of total protein and protein bound carbohydrate components (hexose, hexosamine and sialic acid) were observed in serum, lung and liver tissues. Dietary supplementation of piperine (50 mg/kg body weight) to B(a)p administered animals decreased the total protein and protein bound carbohydrate levels of lung cancer bearing animals in during initiation and post-initiation phases. Our data suggest that piperine may extend its chemopreventive effect through modulating the protein bound carbohydrate levels, as they are one of the indicators of tumorigenesis.

Topics: Alkaloids; Animals; Antineoplastic Agents; Antioxidants; Benzo(a)pyrene; Benzodioxoles; Glycoproteins; Liver; Lung; Lung Neoplasms; Male; Mice; Piperidines; Polyunsaturated Alkamides

In recent years, considerable emphasis has been focused on identifying new chemopreventive agents, which could be useful for the human population. Piperine is a pure, pungent alkaloid constituent of black and long peppers (piper nigrum and piper longum), which is a most common spice used throughout the world. In the present study, we examined the protective role of piperine during experimental lung carcinogenesis with reference to its effect on DNA damage and detoxification enzyme system. The activities of detoxifying enzymes such as glutathione transferase (GST), quinone reductase (QR) and UDP-glucuronosyl transferase (UDP-GT) were found to be decreased while the hydrogen peroxide level was increased in the lung cancer bearing animals. Supplementation of piperine (50 mg/kg bwt) enhanced the detoxification enzymes and reduced DNA damage as determined by single cell electrophoresis. Furthermore, the DNA-Protein cross links which was found to be high in lung cancer bearing animals was also modulated upon supplementation with piperine. Our present results explain the understanding of unique association between anti-peroxidative effect of piperine and ultimately the capability of piperine to prevent cancer.

Topics: Administration, Oral; Alkaloids; Animals; Benzo(a)pyrene; Benzodioxoles; DNA; DNA Damage; Down-Regulation; Glucuronosyltransferase; Glutathione Transferase; Hydrogen Peroxide; Lung Neoplasms; Male; Mice; NAD(P)H Dehydrogenase (Quinone); Piperidines; Polyunsaturated Alkamides

Piperine is a major component of black (Piper nigrum Linn) and long pepper (Piper longum Linn) used widely in various systems of traditional medicine. We have evaluated the effect of piperine on mitochondrial tricarboxylic acid cycle and phase I and glutathione-metabolizing enzymes in Benzo(a)pyrene induced experimental lung carcinogenesis in swiss albino mice. Lung cancer bearing mice showed a significant decrease in the activities of mitochondrial enzymes-isocitrate dehydrogenase (ICDH), -ketoglutarate dehydrogenase (KDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and significantly increased NADPH-Cytochorome reductase (NADPH-C reductase), cytochrome P450 (cyt-p450) and cytochrome b5(cyt-b5). The activities of glutathione-metabolizing enzymes glutathione peroxidase(GPx), glutathione reductase (GR) and glucose-6-phospho dehydrogenase(G6PDH) were significantly lowered in lung-cancer bearing mice when compared with control mice. Piperine supplementation to tumour-induced animals significantly lowered the phase-I enzymes (NADPH-C reductase, cyt-p450 and cyt-b5)) and there was a rise in glutathione-metabolizing enzymes (GPx, GR and G6PDH), which indicated an antitumour and anti-cancer effect. Comparison of normal control mice and mice administered piperine only as drug control showed no significant variations in enzyme activities. Piprine administration to benzo(a)pyrene induced animals significantly increased the activities of mitochondrial enzymes, thereby suggesting its role in mitochondrial energy production.

Topics: Alkaloids; Animals; Anticarcinogenic Agents; Benzo(a)pyrene; Benzodioxoles; Citric Acid Cycle; Cytochrome P-450 Enzyme Inhibitors; Enzymes; Glutathione; Liver; Lung Neoplasms; Male; Mice; Mitochondria; Piperidines; Polyunsaturated Alkamides

Chemoprevention has emerged as a very effective preventive measure against carcinogenesis. Many bioactive compounds present in edible as well in herbal plants have revealed their cancer chemopreventive potential. In the present study, our goal was to investigate the impact of piperine, a principle ingredient of pepper, on alterations of mitochondrial antioxidant system and lipid peroxidation in Benzo(a)pyrene (B(a)P) induced experimental lung carcinogenesis. Oral supplementation of piperine (50 mg/kg body weight) effectively suppressed lung carcinogenesis in B(a)p induced mice as revealed by the decrease in the extent of mitochondrial lipid peroxidation and concomitant increase in the activities of enzymatic antioxidants (superoxide dismutase, catalase and glutathione peroxidase) and non enzymatic antioxidant (reduced glutathione, vitamin E and vitamin C) levels when compared to lung carcinogenesis bearing animals. Our data suggests that piperine may extent its chemopreventive effect by modulating lipid peroxidation and augmenting antioxidant defense system.

Topics: Alkaloids; Animals; Antineoplastic Agents; Antioxidants; Benzo(a)pyrene; Benzodioxoles; Disease Models, Animal; Lipid Peroxidation; Lung Neoplasms; Male; Mice; Mitochondria; Phytotherapy; Piperidines; Plants, Medicinal; Polyunsaturated Alkamides

The current study was designed to evaluate the effects of oral supplementation of the piperine on lung tumour initiation by orally applied benzo(a)pyrene (B(a)p). To evaluate the effects of orally supplemented piperine on lung tumour initiation by B(a)p, its effects on ATPase enzymes were first evaluated. Lung cancer bearing mice showed an increase in erythrocyte membrane and tissues ATPase enzymes (Na(+)/K(+)-ATPases, Mg(2+)-ATPases and Ca(2+)-ATPases). Na(+) K-ATPase and Mg-ATPase enzyme activities were decreased and calcium ATPase increased (P < 0.05) in erythrocyte membrane and tissues of lung cancer bearing animals compared with control groups. The elevation of these enzyme activities in membrane and tissues were indicative of the persistent deteriorating effect of B(a)p in cancer bearing animals. These enzyme activities were reversed to near normal control values in animals treated with piperine (50 mg/kg body weight). It is apparent that the beneficial effect of piperine is primarily exerted on the during initiation phase and post-initiation stage of B(a)p induced lung carcinogenesis. Overall, these data indicative that piperine has chemopreventive effects when administered orally on lung cancer bearing animals.

Topics: Alkaloids; Animals; Anticarcinogenic Agents; Benzo(a)pyrene; Benzodioxoles; Ca(2+) Mg(2+)-ATPase; Calcium-Transporting ATPases; Carcinogens; Enzyme Inhibitors; Erythrocyte Membrane; Lipid Peroxidation; Lung Neoplasms; Male; Mice; Piperidines; Polyunsaturated Alkamides; Sodium-Potassium-Exchanging ATPase

The cytoprotective effect of piperine on benzo[a]pyrene (B[a]P) induced experimental lung cancer was investigated in male Swiss albino mice. Oral administration of piperine (100 mg/kg body wt.) effectively suppressed lung cancer initiated with B[a]P as revealed by the decrease in the extent of lipid peroxidation with concomitant increase in the activities of enzymatic antioxidants (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymatic antioxidant (reduced glutathione, vitamin E and vitamin C) levels when compared to lung cancer bearing animals. Our data suggest that piperine may extend its chemopreventive effect by modulating lipid peroxidation and augmenting antioxidant defense system.

Topics: Administration, Oral; Alkaloids; Animals; Antioxidants; Benzo(a)pyrene; Benzodioxoles; Cytoprotection; Lipid Peroxidation; Lung; Lung Neoplasms; Male; Mice; Phytotherapy; Piperidines; Polyunsaturated Alkamides

The effect of piperine on the inhibition of lung metastasis induced by B16F-10 melanoma cells was studied in C57BL/6 mice. Simultaneous administration of the compound with tumor induction produced a significant reduction (95.2%) in tumor nodule formation. Increased lung collagen hydroxyproline (22.37 microg/mg protein) in the metastasized lungs of the control animals compared to normal animals (0.95 microg/mg protein) was significantly reduced (2.59 microg/mg protein) in the piperine-treated animals. The high amount of uronic acid (355.83 microg/100 mg tissue) in the metastasized control animals was significantly reduced (65 microg/100 mg tissue) in the animals treated with piperine. Lung hexosamine content was also significantly reduced in the piperine-treated animals (0.98 mg/100 mg lyophilized tissue) compared to the untreated tumor-bearing animals (4.2 mg/100 mg lyophilized tissue). The elevated levels of serum sialic acid and serum gamma glutamyl transpeptidase activity in the untreated control animals was significantly reduced in the animals treated with piperine. The piperine-treated animals even survived the experiment (90 days). Histopathology of the lung tissue also correlated with the lifespan of the drug-treated animals. Our results demonstrate the antimetastatic activity of piperine, an alkaloid present in plants such as Piper nigrum and Piper longum.

Topics: Alkaloids; Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzodioxoles; Cell Division; gamma-Glutamyltransferase; Lung Neoplasms; Melanoma, Experimental; Mice; Mice, Inbred C57BL; N-Acetylneuraminic Acid; Piperidines; Polyunsaturated Alkamides; Tumor Cells, Cultured