Beta-Lapachone

Beta lapachone is viewed as a promising anti cancer drug for cancer prevention and may improve the clinical outcome of patients with cancer.

Beta Lapachone, a compound found in the bark of the South American Pau D’Arco tree, is a potent activator of the NQ01 protein.  The pharma industry has turned its sights on Beta Lapachone as a potential treatment for a variety of cancers. Its benefits are based on being a potent activator of the NQ01 protein and produces ROS in cancer cells, but reduces ROS in non-cancer cells.  NQ01 influences the NAD/NADH ratio, now thought to be more important than merely raising NAD levels, which precursors NR and NMN are said to do (Sinclair and Guarente). 

BA paper in the journal PLOS one, published October 11, 2012 -Jeong-sook Lee et al, describes beta lapachone as a modulator of NAD metabolism, which prevented health declines in aged mice. It prevented age dependent decline of motor and cognitive function in aged mice. Mice fed the beta lapachonoe diet showed similar changes in gene expression to the calorie restriction group (fed 70% of control diet).  In addition, aging related markers in blood, such as increased glucose cholesterol and leptin associated with increased body fats were significantly lowered in the BL and CR groups.

Beta lapachone mimics the beneficial effects of calorie restriction on molecular, cellular and behavioral functions of aged mice. These results strongly support the NAD*/NADH theory of aging that the deregulation of the ratio leads to aging and age related abnormalities, and suggests that the dietary and medical administration of this NQ01 co-substrate (beta lapachone) could be a useful strategy for enhancing the quality of like in aging people.

In comparison  to CR (calorie restriction) mice fed beta lapachone showed a 17% increase in the mean survival period comnpared the control mice.  Whereas the CR group showed a 10% increase, suggesting that BL was more effective than CR in increasing survival rate.

In a May 2016 article published by the American Diabetes Association, Beta Lapachone prevents diet-induced obesity by increasing energy expenditure and stimulating the browning of white adipose tissue via down-regulation of miR-382 expression.

 

The following is a list of links to past and ongoing studies and clinical trials for beta-lapachone

 

Miscellaneous

• Preclinical Pharmacokinetic Evaluation of β-Lapachone: Characteristics of Oral Bioavailability and First-Pass Metabolism in Rats.
• Cancer therapy with beta-lapachone.
• β-Lapachone attenuates mitochondrial dysfunction in MELAS cybrid cells.
• Beta-lapachone inhibits pathological retinal neovascularization in oxygen-induced retinopathy via regulation of HIF-1α.
• Beta-lapachone, a modulator of NAD metabolism, prevents health declines in aged mice.
• β-lapachone accelerates the recovery of burn-wound skin.
• Corpus cavernosal smooth muscle relaxation effect of a novel AMPK activator, beta-lapachone.
• Beta-lapachone suppresses radiation-induced activation of nuclear factor-kappaB.
• In vitro and in vivo wound healing-promoting activities of beta-lapachone.
• Suppression of tumor necrosis factor-activated nuclear transcription factor-kappaB, activator protein-1, c-Jun N-terminal kinase, and apoptosis by ...

Cancer/Hypoxia

• ARQ-761 Treatment With Gemcitabine/Nab-Paclitaxel Chemotherapy In Pancreatic Cancer
• ARQ 501 in Combination With Gemcitabine in Subjects With Pancreatic Cancer
• Inhibition of radiation-induced neoplastic transformation by beta-lapachone.
• β-lapachone suppresses the proliferation of human malignant melanoma cells by targeting specificity protein 1.
• Tumor-selective use of DNA base excision repair inhibition in pancreatic cancer using the NQO1 bioactivatable drug, β-lapachone.
• Identification of β-Lapachone Analogs as Novel MALT1 Inhibitors To Treat an Aggressive Subtype of Diffuse Large B-Cell Lymphoma.
• Beta-Lapachone Suppresses Non-small Cell Lung Cancer Proliferation through the Regulation of Specificity Protein 1.
• Combinative effects of β-Lapachone and APO866 on pancreatic cancer cell death through reactive oxygen species production and PARP-1 activation.
• Mitochondrial targeted β-lapachone induces mitochondrial dysfunction and catastrophic vacuolization in cancer cells.
• Downregulation of Sp1 is involved in β-lapachone-induced cell cycle arrest and apoptosis in oral squamous cell carcinoma.
• UDP-glucuronosyltransferase 1A determinates intracellular accumulation and anti-cancer effect of β-lapachone in human colon cancer cells.
• NAMPT inhibition sensitizes pancreatic adenocarcinoma cells to tumor-selective, PAR-independent metabolic catastrophe and cell death induced by β-l...
• eIF2 kinases mediate β-lapachone toxicity in yeast and human cancer cells.
• Esterase-activatable β-lapachone prodrug micelles for NQO1-targeted lung cancer therapy.
• Mechanistic studies of cancer cell mitochondria- and NQO1-mediated redox activation of beta-lapachone, a potentially novel anticancer agent.
• β-lapachone-Induced Apoptosis of Human Gastric Carcinoma AGS Cells Is Caspase-Dependent and Regulated by the PI3K/Akt Pathway.
• β-Lapachone induces programmed necrosis through the RIP1-PARP-AIF-dependent pathway in human hepatocellular carcinoma SK-Hep1 cells.
• The Tumor-Selective Cytotoxic Agent β-Lapachone is a Potent Inhibitor of IDO1.
• Effects of β-lapachone, a new anticancer candidate, on cytochrome P450-mediated drug metabolism.
• Synergistic enhancement of antitumor effect of β-Lapachone by photodynamic induction of quinone oxidoreductase (NQO1).
• Cytotoxicity of lapachol, β-lapachone and related synthetic 1,4-naphthoquinones against oesophageal cancer cells.
• Administration of the optimized β-Lapachone-poloxamer-cyclodextrin ternary system induces apoptosis, DNA damage and reduces tumor growth in a human...
• β-Lapachone analogs with enhanced antiproliferative activity.
• Growth inhibitory effects of 3'-nitro-3-phenylamino nor-beta-lapachone against HL-60: a redox-dependent mechanism.
• β-Lapachone-induced reactive oxygen species (ROS) generation mediates autophagic cell death in glioma U87 MG cells.
• Beta-lapachone micellar nanotherapeutics for non-small cell lung cancer therapy.
• Beta-lapachone (LAPA) decreases cell viability and telomerase activity in leukemia cells: suppression of telomerase activity by LAPA.
• Paclitaxel and beta-lapachone synergistically induce apoptosis in human retinoblastoma Y79 cells by downregulating the levels of phospho-Akt.
• Involvement of endoplasmic reticulum stress and activation of MAP kinases in beta-lapachone-induced human prostate cancer cell apoptosis.
• Comparative studies of the effects of Tabebuia avellanedae bark extract and beta-lapachone on the hematopoietic response of tumour-bearing mice.
• Induction of Egr-1 is associated with anti-metastatic and anti-invasive ability of beta-lapachone in human hepatocarcinoma cells.
• Beta-lapachone inhibits proliferation and induces apoptosis in retinoblastoma cell lines.
• Selective induction of necrotic cell death in cancer cells by beta-lapachone through activation of DNA damage response pathway.
• Beta-lapachone, a quinone isolated from Tabebuia avellanedae, induces apoptosis in HepG2 hepatoma cell line through induction of Bax and activation...
• beta-lapachone induces growth inhibition and apoptosis in bladder cancer cells by modulation of Bcl-2 family and activation of caspases.
• Development of beta-lapachone prodrugs for therapy against human cancer cells with elevated NAD(P)H:quinone oxidoreductase 1 levels.
• Down-regulation of cyclooxygenase-2 and telomerase activity by beta-lapachone in human prostate carcinoma cells.
• Growth inhibition of A549 human lung carcinoma cells by beta-lapachone through induction of apoptosis and inhibition of telomerase activity.
• Efficacy of beta-lapachone in pancreatic cancer treatment: exploiting the novel, therapeutic target NQO1.
• beta-Lapachone-induced apoptosis is associated with activation of caspase-3 and inactivation of NF-kappaB in human colon cancer HCT-116 cells.
• Suppression of human prostate cancer cell growth by beta-lapachone via down-regulation of pRB phosphorylation and induction of Cdk inhibitor p21(WA...
• Selective killing of cancer cells by beta -lapachone: direct checkpoint activation as a strategy against cancer.
• beta-lapachone, a novel plant product, overcomes drug resistance in human multiple myeloma cells.
• Potent induction of apoptosis by beta-lapachone in human multiple myeloma cell lines and patient cells.
• beta-Lapachone-induced apoptosis in human prostate cancer cells: involvement of NQO1/xip3.
• beta-lapachone induces cell cycle arrest and apoptosis in human colon cancer cells.
• Potent inhibition of tumor survival in vivo by beta-lapachone plus taxol: combining drugs imposes different artificial checkpoints.
• Release of mitochondrial cytochrome C in both apoptosis and necrosis induced by beta-lapachone in human carcinoma cells.
• Induction of apoptosis in MCF-7:WS8 breast cancer cells by beta-lapachone.
• Involvement of hydrogen peroxide in topoisomerase inhibitor beta-lapachone-induced apoptosis and differentiation in human leukemia cells.
• beta-Lapachone induced cell death in human hepatoma (HepA2) cells.
• Induction of apoptosis by beta-lapachone in human prostate cancer cells.
• Beta-lapachone-mediated apoptosis in human promyelocytic leukemia (HL-60) and human prostate cancer cells: a p53-independent response.
• beta-Lapachone: synthesis of derivatives and activities in tumor models.
• beta-Lapachone enhancement of lipid peroxidation and superoxide anion and hydrogen peroxide formation by sarcoma 180 ascites tumor cells.

Cortisol/Diabetes/Obesity

• Beta-lapachone, a specific competitive inhibitor of ligand binding to the glucocorticoid receptor.

Inflammation/CVD

• Cytoprotective effect of β-lapachone by inducing heme oxygenase-1 expression and AMP-activated protein kinase activation in human endothelial cells.
• β-Lapachone ameliorates lipotoxic cardiomyopathy in acyl CoA synthase transgenic mice.
• β-Lapachone, a substrate of NAD(P)H:quinone oxidoreductase, induces anti-inflammatory heme oxygenase-1 via AMP-activated protein kinase activation ...
• Synthesis and anti-inflammatory evaluations of β-lapachone derivatives.
• Effects of β-lapachone on the production of Th1 and Th2 cytokines in C57BL/6 mice.
• Anti-inflammatory and anti-arthritic activities of 3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione (β-lapachone).
• Inhibition of inducible nitric oxide synthase by beta-lapachone in rat alveolar macrophages and aorta.

Neurological/Mental/Mood

• β-Lapachone suppresses neuroinflammation by modulating the expression of cytokines and matrix metalloproteinases in activated microglia.
• β-Lapachone ameliorization of experimental autoimmune encephalomyelitis.
• Anti-inflammatory effects of beta-lapachone in lipopolysaccharide-stimulated BV2 microglia.

Endotoxin/Gastrointestinal/Liver/Pancreas/Kidney

• β-Lapachone ameliorates murine cisplatin nephrotoxicity: NAD⁺, NQO1, and SIRT1 at the crossroads of metabolism, injury, and inflammation.
• β-Lapachone alleviates alcoholic fatty liver disease in rats.
• beta-Lapachone reduces endotoxin-induced macrophage activation and lung edema and mortality.

Anti-viral/Anti-bacterial/Anti-parasitic/Anti-fungal

• Assessment of β-lapachone loaded in lecithin-chitosan nanoparticles for the topical treatment of cutaneous leishmaniasis in L. major infected BALB/...
• ANTHELMINTIC ACTIVITY OF LAPACHOL, β-LAPACHONE AND ITS DERIVATIVES AGAINST Toxocara canis LARVAE.
• Synthesis and anti-Trypanosoma cruzi activity of new 3-phenylthio-nor-β-lapachone derivatives.
• Ultrastructural analysis of β-lapachone-induced surface membrane damage in male adult Schistosoma mansoni BH strain worms.
• β-Lapachone: a naphthoquinone with promising antischistosomal properties in mice.
• β-Lapachone activity in synergy with conventional antimicrobials against methicillin resistant Staphylococcus aureus strains.
• Identification of nor-β-lapachone derivatives as potential antibacterial compounds against Enterococcus faecalis clinical strain.
• Activity of β-lapachone derivatives against rifampicin-susceptible and -resistant strains of Mycobacterium tuberculosis.
• The evaluation of quinonoid compounds against Trypanosoma cruzi: synthesis of imidazolic anthraquinones, nor-beta-lapachone derivatives and beta-la...
• Antifungal activity of the naphthoquinone beta-lapachone against disseminated infection with Cryptococcus neoformans var. neoformans in dexamethaso...
• In vitro synergic effect of beta-lapachone and isoniazid on the growth of Mycobacterium fortuitum and Mycobacterium smegmatis.
• Trypanosoma cruzi: activities of lapachol and alpha- and beta-lapachone derivatives against epimastigote and trypomastigote forms.
• Mitochondrial disruption and DNA fragmentation in Trypanosoma cruzi induced by naphthoimidazoles synthesized from beta-lapachone.
• Antiplasmodial activity of naphthoquinones related to lapachol and beta-lapachone.
• Effect of a beta-lapachone-derived naphthoimidazole on Trypanosoma cruzi: identification of target organelles.
• Studies on the trypanocidal activity of semi-synthetic pyran[b-4,3]naphtho[1,2-d]imidazoles from beta-lapachone.
• Antimalarial activity of phenazines from lapachol, beta-lapachone and its derivatives against Plasmodium falciparum in vitro and Plasmodium berghei...
• A trypanocidal phenazine derived from beta-lapachone.
• Comparison of antibacterial and antifungal activities of lapachol and beta-lapachone.
• Evaluation of the toxicity of 3-allyl-beta-lapachone against Trypanosoma cruzi bloodstream forms.
• Effect of beta-lapachone on superoxide anion and hydrogen peroxide production in Trypanosoma cruzi.
• Generation of superoxide anions and hydrogen peroxide from beta-lapachone in bacteria.
• Lipid peroxidation and the generation of free radicals, superoxide anion, and hydrogen peroxide in beta-lapachone-treated Trypanosoma cruzi epimast...
• beta-Lapachone, an inhibitor of oncornavirus reverse transcriptase and eukaryotic DNA polymerase-alpha. Inhibitory effect, thiol dependence and spe...
• Effect of beta-lapachone on hydrogen peroxide production in Trypanosoma cruzi.
• Trypanosoma cruzi: ultrastructural and metabolic alterations of epimastigotes by beta-lapachone.