PMID: 

MedGenMed. 2000 May 4 ;2(2):E2. Epub 2000 May 4. PMID: 11104448

Abstract Title: 

Case-control study on radiology work, medical x-ray investigations, and use of cellular telephones as risk factors for brain tumors.

Abstract: 

CONTEXT: Ionizing radiation is a well-established risk factor for brain tumors. During recent years, microwave exposure from the use of cellular telephones has been discussed as a potential risk factor.OBJECTIVE: To determine risk factors for brain tumors.DESIGN: A case-control study, with exposure assessed by questionnaires.PARTICIPANTS: A total of 233 currently living men and women, aged 20 to 80 years, were included. The case patients had histopathologically verified brain tumors and lived in the Uppsala-Orebro region (1994-1996) or the Stockholm region (1995-1996). Two matched controls to each case were selected from the Swedish Population Register.MAIN OUTCOME MEASURES: Ionizing radiation and use of cellular telephones as risk factors for brain tumors.RESULTS: A total of 209 cases (90%) and 425 controls (91%) answered the questionnaire. Work as a physician yielded an odds ratio (OR) of 6.00, with a 95% confidence interval (CI) of 0.62 to 57.7. All three case patients had worked with fluoroscopy. Radiotherapy of the head and neck region yielded an OR of 3.61 (95% CI, 0.65-19.9). Medical diagnostic x-ray examination of the same area yielded an OR of 2.10 (95% CI, 1.25-3.53), with a tumor induction period of 5 years or more. Chemical industry work yielded an OR of 4.10 (95% CI, 1.25-13.4), and laboratory work yielded an OR of 3.21 (95% CI, 1.16-8.85). Ipsilateral use of cellular telephones increased the risk for tumors in the temporal, temporoparietal, and occipital lobes (OR, 2.42; 95% CI, 0.97-6.05), ie, the anatomic areas with highest exposure to microwaves from a mobile telephone. The result was further strengthened (OR, 2.62; 95% CI, 1.02-6.71) in a multivariate analysis that included laboratory work and medical diagnostic x-ray investigations of the head and neck.CONCLUSION: Exposure to ionizing radiation, work in laboratories, and work in the chemical industry increased the risk of brain tumors. Use of a cellular telephone was associated with an increased risk in the anatomic area with highest exposure.

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PMID: 

Biochem Pharmacol. 2018 09 ;155:494-509. Epub 2018 Jul 31. PMID: 30071202

Abstract Title: 

Cardamonin, a natural flavone, alleviates inflammatory bowel disease by the inhibition of NLRP3 inflammasome activation via an AhR/Nrf2/NQO1 pathway.

Abstract: 

The present study aimed to evaluate the anti-colitis effect and underlying mechanisms of cardamonin, a natural flavone isolated from Alpinia katsumadai Hayata. The results showed that oral cardamonin significantly inhibited dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice, evidenced by improvement of disease activity index scores, myeloperoxidase activity, length shortening and histopathological changes of colons. A rectal administration of cardamonin also exhibited marked anti-colitis effect, suggesting that oral cardamonin might function in a prototype form. Cardamonin down-regulated levels of IL-1β, TNF-α, IL-6, NLRP3, cleaved caspase-1, ASC, cleaved IL-1β in colons of colitis mice. In vitro, cardamonin inhibited NLRP3 inflammasome activation in THP-1 and bone marrow-derived macrophages. It acted as an AhR activator, enhanced dissociation of AhR/HSP90 complexes, association of AhR/ARNT complexes, AhR nuclear translocation, XRE reporter gene activity, and AhR/ARNT/XRE DNA binding activity in THP-1 cells. The AhR antagonist CH223191 obviously abolished NLRP3 inflammasome activation inhibited by cardamonin. Furthermore, cardamonin elevated levels of Nrf2 and its target genes NQO1, Trx1, SOD2, HO-1, and the effect on NQO1 was the most obvious. The relationship of cardamonin-adjusted AhR activation, expressions of Nrf2 and NQO1, and NLRP3 inflammasome activation was confirmed by using CH223191, siAhR, ML385 and siNQO1, respectively. Finally, CH223191 was shown to abolish amelioration of cardamonin on DSS- and TNBS-induced colitis, inhibition of NLRP3 inflammasome activation and up-regulation of Nrf2 and NQO1 levels in colons. Taken together, cardamonin ameliorated colitis in mice through the activation of AhR/Nrf2/NQO1 pathway and consequent inhibition of NLRP3 inflammasome activation.

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PMID: 

Arch Environ Health. 2004 Mar ;59(3):132-7. PMID: 16121902

Abstract Title: 

Cellular and cordless telephone use and the association with brain tumors in different age groups.

Abstract: 

The authors' case-control study on the possible association between brain tumors and mobile and cordless telephone use included 1,617 patients and 1,617 controls. A questionnaire was answered by 1,429 (88%) cases and 1,470 (91%) controls. Use of analog cellular telephones yielded an odds ratio (OR) for brain tumors of 1.31, 95% confidence interval (CI) = 1.04-1.64, increasing for ipsilateral use to OR = 1.65, 95% CI = 1.19-2.30. The authors found the highest risk for the 20-29-yr age group, with OR = 5.91, 95% CI = 0.63-55 for ipsilateral use of analog phones. The highest risks were associated with>5-year latency period in the 20-29-yr age group for analog phones (OR = 8.17, 95% CI = 0.94-71), and cordless phones (OR = 4.30, 95% CI = 1.22-15).

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PMID: 

Pharmacol Rep. 2018 Oct ;70(5):908-916. Epub 2018 Apr 17. PMID: 30099297

Abstract Title: 

Autophagy induced by cardamonin is associated with mTORC1 inhibition in SKOV3 cells.

Abstract: 

BACKGROUND: The mammalian target of rapamycin (mTOR) integrates energy level to modulate cell proliferation and autophagy. Cardamonin exhibits anti-proliferative activity through inhibiting mTOR. In this study, the effect of cardamonin on autophagy and its mechanism on mTOR inhibition were investigated.METHODS: Cell viability and proliferation were measured by MTT assay and BrdU incorporation, respectively. Cell apoptosis was assayed by flow cytometry and cell autophagy was detected by electron microscopy and GFP-LC3 fluorescence. The mechanism of cardamonin on mTORC1 inhibition was investigated by Raptor siRNA and Raptor over-expression.RESULTS: The cell viability and proliferation were inhibited by cardamonin. The autophagosomes and the protein level of LC3-II were increased by cardamonin. Cell apoptosis and the levels of cleaved PARP and Caspase-3 were increased by cardamonin. Cardamonin inhibited the phosphorylation of mTOR and ribosome S6 protein kinase 1 (S6K1) as well as the protein level of regulatory associated protein of mTOR (Raptor). However, cardamonin had no effect on the component of mTORC2 and its downstream substrate Akt. The inhibitory effect of cardamonin on the phosphorylation of mTOR and S6K1 was eliminated by Raptor knockdown with siRNA, whereas this effect of cardamonin was stronger than that of rapamycin and AZD8055 in Raptor over-expression cells. Cell viability was inhibited by cardamonin in both Raptor knockdown and Raptor over-expression cells, which was consistent with the inhibitory effect of cardamonin on mTOR.CONCLUSION: These findings demonstrated that the autophagy induced by cardamonin was associated with mTORC1 inhibition through decreasing the protein level of Raptor in SKOV3 cells.

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PMID: 

Int J Radiat Biol. 2002 Oct ;78(10):931-6. PMID: 12465658

Abstract Title: 

Case-control study on the use of cellular and cordless phones and the risk for malignant brain tumours.

Abstract: 

PURPOSE: To investigate the use of cellular and cordless phones and the risk for malignant brain tumours.MATERIALS AND METHODS: A case-control study was performed on 649 patients aged 20-80 years of both sexes with malignant brain tumour diagnosed from 1 January 1997 to 30 June 2000. All patients were alive during the time of the study and had histopathology verified brain tumours. One matched control to each case was selected from the Swedish Population Register. The study area was the Uppsala-Orebro, Stockholm, Linköping and Göteborg medical regions of Sweden.RESULTS: Exposure was assessed by a questionnaire answered by 588 (91%) cases and 581 (90%) controls. Phone usage was defined as 'ever use' and usage starting within 1 year before diagnosis was disregarded. Overall, no significantly increased risks were found: analogue cellular phones yielded an odds ratio (OR)=1.13, 95% confidence interval (CI)=0.82-1.57, digital cellular phones OR=1.13, CI=0.86-1.48, and cordless phones OR=1.13, CI=0.85-1.50. For ipsilateral (same side) radiofrequency exposure, analogue mobile phones gave OR=1.85, CI=1.16-2.96, for all malignant brain tumours. For astrocytoma, this risk was OR=1.95, CI=1.12-3.39. For all malignant brain tumours, digital mobile phones yielded OR=1.59, CI=1.05-2.41, and cordless phones yielded OR=1.46, CI=0.96-2.23, in the analysis of ipsilateral exposure.CONCLUSION: The ipsilateral use of an analogue cellular phone yielded a significantly increased risk for malignant brain tumours.

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PMID: 

Pharmazie. 2018 09 1 ;73(9):508-512. PMID: 30223933

Abstract Title: 

Cardamonin protects against adverse cardiac remodeling through mTORC1 inhibition in mice with myocardial infarction.

Abstract: 

The mTORC1-dependent signaling pathway is mainly involved in the adverse left ventricular remodeling (ALVR) process after myocardial infarction (MI). However, whether mTORC1 inhibition by cardamonin attenuates ALVR after MI is still not reported. Twenty mice were randomly assigned into three groups: sham group (10 ml/kg/day PBS, n=6), model group (MI and 10 ml/kg/day PBS, n=7) and cardamonin-treated group (MI and 20 mg/kg/day cardamonin, n=7). All groups received an intraperitoneal injection accordingly for two weeks. Heart and body mass were measured. Cardiac function was assessed by echocardiography. The collagen deposition, area of cardiomyocytes and cell apoptosis of border area were evaluated using Masson's staining, WGA staining and TUNEL assay, respectively. The 4E-binding protein 1 (4E-BP1) and ribosomal S6 (S6) in myocardium were determined by western blot. mTOR-Raptor association was tested by co-immunoprecipitation assay in H9C2 cell line. Treatment with cardamonin, MI mice displayed that heart hypertrophy and heart dysfunction were alleviated, and cardiac fibrosis, cardiomyocyte size and cell apoptosis of border area were decreased (P

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PMID: 

Anticancer Drugs. 2019 Mar ;30(3):241-250. PMID: 30640793

Abstract Title: 

Cardamonin inhibits the proliferation and metastasis of non-small-cell lung cancer cells by suppressing the PI3K/Akt/mTOR pathway.

Abstract: 

Cardamonin, a natural chalcone compound, has been reported to exert anticancer effects in several cancers. However, the specific pharmacological actions of cardamonin on human non-small-cell lung cancer (NSCLC) and the potential mechanisms still remain obscure. Here, we investigated the antineoplastic role of cardamonin in NSCLC both in vitro and in vivo. The proliferation of five NSCLC cell lines was inhibited in a dose-dependent and time-dependent manner with cardamonin treatment. In A549 and H460 cells, cardamonin induced apoptosis by activating caspase-3, upregulating Bax, and downregulating Bcl-2. In addition, cardamonin arrested cells in the G2/M phase and inhibited the expression levels of cyclin D1/CDK4. Moreover, cell migration and invasion were suppressed by reversing epithelial-mesenchymal transition with cardamonin treatment. Further study showed that cardamonin reduced the phosphorylation levels of the downstream effectors of phosphoinositide 3-kinase (PI3K), including protein kinase-B (Akt/PKB) and mammalian target of rapamycin (mTOR). Moreover, in the H460 xenograft model, cardamonin significantly retarded tumor growth. Also, in tumor tissues, we found that cardamonin treatment decreased the expression rates of Ki-67, p-Akt, and p-mTOR. These data suggest that cardamonin suppressed NSCLC cell proliferation and inhibited metastasis partly by restraining the PI3K/Akt/mTOR pathway and it might be an effective therapeutic compound for NSCLC in the future.

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PMID: 

Neuroepidemiology. 2003 Mar-Apr;22(2):124-9. PMID: 12629278

Abstract Title: 

Vestibular schwannoma, tinnitus and cellular telephones.

Abstract: 

Cases with tinnitus after using analogue cellular telephones are presented. An increased odds ratio of 3.45, 95% confidence interval (CI) 1.77-6.76, was found for vestibular schwannoma (VS) associated with the use of analogue cell phones. During the time period 1960-1998, the age-standardized incidence of VS in Sweden significantly increased yearly by +2.53% (CI 1.71-3.35). A significant increase in the incidence of VS was only found for the latter of the two time periods 1960-1979 and 1980-1998. For all other brain tumors taken together, the incidence significantly increased yearly by +0.80% (CI 0.59-1.02) for the time period 1960-1998, although the increase was only significant for benign tumors other than VS during 1960-1979.

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PMID: 

Am J Chin Med. 2019 ;47(3):635-656. Epub 2019 Apr 25. PMID: 31023073

Abstract Title: 

Cardamonin Induces Cell Cycle Arrest, Apoptosis and Alters Apoptosis Associated Gene Expression in WEHI-3 Mouse Leukemia Cells.

Abstract: 

Cardamonin, the chalcone class, is one of the natural components from the spicy herbaceous plant (Griff) and has anticancer activities in many human cancer cell lines. There is, however, no information to show that cardamonin induces cell apoptosis and alters apoptosis associated gene expressions in mouse leukemia cells. Thus, we investigated the effects of cardamonin on the apoptotic cell death and associated gene expression in mouse leukemia WEHI-3 cells. Results indicated that cardamonin decreased total viable cell numberinduced cell morphological changes and apoptotic cell death in WEHI-3 cells that were assay by contrast-phase microscopy and flow cytometry examinations, respectively. The flow cytometry assay indicated that cardamonin increased reactive oxygen species (ROS) and Caproduction, decreased the levels of mitochondrial membrane potential (and increased caspase-3, -8 and -9 activities in WEHI-3 cells. Western blotting was performed to analyze expression of relevant pro- and anti-apoptotic proteins and results showed that cardamonin decreased anti-apoptotic protein of Bcl-2 but increased pro-apoptotic protein of Bax in WEHI-3 cells. Furthermore, cardamonin increased cytochrome c, AIF and Endo G release, increased GRP78, caspase-12 that were associated with ER stress and increased Fas, Fas-Ligand and FADD expression. Furthermore, cardamonin increased the gene expressions of(death-associated protein),transmembrane (BAX inhibitor motif containing 4),(autophagy related 5) but decreased the gene expression of(DNA-damage inducible transcript 3),(DNA-damage-inducible transcript 4),(BCL2-associated athanogene 6),[BCL2-like 13 (apoptosis facilitator)] and(BRCA1-associated ATM activator 1) that are associated with apoptosis pathways. Based on those findings, we may suggest cardamonin induced apoptotic cell death through Fas and Fas-Ligand-, caspase- and mitochondria-dependently pathways and also affects the apoptotic gene expression in WEHI-3 cells.

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PMID: 

Occup Environ Med. 2004 Aug ;61(8):675-9. PMID: 15258273

Abstract Title: 

No association between the use of cellular or cordless telephones and salivary gland tumours.

Abstract: 

AIM: To investigate the association between the use of cellular or cordless telephones and the risk for salivary gland tumours.METHODS: Cases were assessed from the six regional cancer registries in Sweden. Four controls matched for sex and age in five year age groups were selected for each case. A total of 293 living cases and 1172 controls were included.RESULTS: There were 267 (91%) participating cases and 1053 (90%) controls. Overall no significantly increased risk was found. Odds ratios were 0.92 (95% CI 0.58 to 1.44) for use of analogue phones, 1.01 (95% CI 0.68 to 1.50) for use of digital phones, and 0.99 (95% CI 0.68 to 1.43) for use of cordless phones. Similar results were found for different salivary gland localisations. No effect of tumour induction period or latency was seen, although few subjects reported use for more than 10 years.CONCLUSIONS: No association between the use of cellular or cordless phones and salivary gland tumours was found, although this study does not permit conclusions for long term heavy use.

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