Enhancement of recombinant myricetin on the radiosensitivity of lung cancer A549 and H1299 cells.

forr√°s: http://www.ncbi.nlm.nih.gov/pubmed/24650056


2014-04-15 12:41:59


Abstract

OBJECTIVE:

Myricetin, a common dietary flavonoid is widely distributed in fruits and vegetables, and is used as a health food supplement based on its immune function, anti-oxidation, anti-tumor, and anti-inflammatory properties. The aim of this study was to investigate the effects of myricetin on combination with radiotherapy enhance radiosensitivity of lung cancer A549 and H1299 cells.

METHODS:

A549 cells and H1299 cells were exposed to X-ray with or without myricetin treatment. Colony formation assays, CCK-8 assay, flow cytometry and Caspase-3 level detection were used to evaluate the radiosensitization activity of myricetin on cell proliferation and apoptosis in vitro. Nude mouse tumor xenograft model was built to assessed radiosensitization effect of myricetin in vivo.

RESULTS:

Compared with the exposed group without myricetin treatment, the groups treated with myricetin showed significantly suppressed cell surviving fraction and proliferation, increased the cell apoptosis and increased Caspase-3 protein expression after X-ray exposure in vitro. And in vivo assay, growth speed of tumor xenografts was significantly decreased in irradiated mice treated with myricetin.

CONCLUSIONS:

The study demonstrated both in vitro and in vivo evidence that combination of myricetin with radiotherapy can enhance tumor radiosensitivity of pulmonary carcinoma A549 and H1299 cells, and myricetin could be a potential radiosensitizer for lung cancer therapy.

VIRTUAL SLIDES:

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5791518001210633.

 


Anticancer potential of Hericium erinaceus extracts against human gastrointestinal cancers.

forr√°s: http://www.ncbi.nlm.nih.gov/pubmed/24631140


2014-04-15 12:36:18


Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Hericium is a genus of mushrooms (fungus) in the Hericiaceae family. Hericium erinaceus (HE) has been used for the treatment of digestive diseases for over 2000 years in China. HE possesses many beneficial functions such as anticancer, antiulcer, antiinflammation and antimicrobial effects, immunomodulation and other activities. The aim of the studies was to evaluate the anticancer efficacy of two extracts (HTJ5 and HTJ5A) from the culture broth of HE against three gastrointestinal cancers such as liver, colorectal and gastric cancers in both of in vitro of cancer cell lines and in vivo of tumor xenografts and discover the active compounds.

MATERIALS AND METHODS:

Two HE extracts (HTJ5 and HTJ5A) were used for the studies. For the study of chemical constituents, the HTJ5 and HTJ5A were separated using a combination of macroporous resin with silica gel, HW-40 and LH-20 chromatography then purified by semipreparative high-performance liquid chromatography (HPLC) and determined by nuclear magnetic resonance (NMR) spectra. For the in vitro cytotoxicity studies, HepG2 and Huh-7 liver, HT-29 colon, and NCI-87 gastric cancer cell lines were used and MTT assay was performed to determine the in vitro cytotoxicity. For in vivo antitumor efficacy and toxicity studies, tumor xenograft models of SCID mice bearing liver cancer HepG2 and Huh-7, colon cancer HT-29 and gastric cancer NCI-87 subcutaneously were used and the mice were treated with the vehicle control, HTJ5 and HTJ5A orally (500 and 1000mg/kg/day) and compared to 5-fluorouraci (5-FU) at the maximum tolerated dose (MTD, 25-30mg/kg/day) intraperitoneally daily for 5 days when the tumors reached about 180-200mg (mm(3)). Tumor volumes and body weight were measured daily during the first 10 days and 2-3 times a week thereafter to assess the tumor growth inhibition, tumor doubling time, partial and complete tumor response and toxicity.

RESULTS:

Twenty-two compounds were obtained from the fractions of HTJ5/HTJ5A including seven cycli dipeptides, five indole, pyrimidines, amino acids and derivative, three flavones, one anthraquinone, and six small aromatic compounds. HTJ5 and HTJ5A exhibited concentration-dependent cytotoxicity in vitro against liver cancer HepG2 and Huh-7, colon cancer HT-29, and gastric cancer NCI-87 cells with the IC50 in 2.50¬Ī0.25 and 2.00¬Ī0.25, 0.80¬Ī0.08 and 1.50¬Ī0.28, 1.25¬Ī0.06 and 1.25¬Ī0.05, and 5.00¬Ī0.22 and 4.50¬Ī0.14mg/ml; respectively. For in vivo tumor xenograft studies, HTJ5 and HTJ5A showed significantly antitumor efficacy against all four xenograft models of HepG2, Huh-7, HT-29 and NCI-87 without toxicity to the host. Furthermore, HTJ5 and HTJ5A are more effective than that of 5-FU against the four tumors with less toxicity.

CONCLUSION:

HE extracts (HTJ5 and HTJ5A) are active against liver cancer HepG2 and Huh-7, colon cancer HT-29 and gastric cancer NCI-87 cells in vitro and tumor xenografts bearing in SCID mice in vivo. They are more effective and less toxic compared to 5-FU in all four in vivo tumor models. The compounds have the potential for development into anticancer agents for the treatment of gastrointestinal cancer used alone and/or in combination with clinical used chemotherapeutic drugs. However, further studies are required to find out the active chemical constituents and understand the mechanism of action associated with the super in vivo anticancer efficacy. In addition, future studies are needed to confirm our preliminary results of in vivo synergistic antitumor efficacy in animal models of tumor xenografts with the combination of HE extracts and clinical used anticancer drugs such as 5-FU, cisplatin and doxurubicin for the treatment of gastrointestinal cancers.

 


Artesunate enhances radiosensitivity of human non-small cell lung cancer A549 cells via increasing NO production to induce cell cycle arrest at G2/M phase.

forr√°s: http://www.ncbi.nlm.nih.gov/pubmed/21907831


2014-03-11 14:01:56


The resistance of non-small cell lung cancer (NSCLC) to radiation is the major reason for radiotherapy failure of this kind cancer. Currently, there is no effective radiosensitizer in clinical use. Artemisinin and its derivates enhance radiotherapeutic effect in some kinds of tumors; however, whether artemisinin and its derivates can enhance the radiosensitivity of NSCLC remains unknown. Therefore, in the present experiments, artemisinin and its derivatives were firstly screened for their radiosensitization on NSCLC A549 (A549) cells and then the possible mechanisms were investigated. Our results showed that artesunate enhance radiosensitivity of A549 cells in vitro among artemisinin and its derivatives, and artesunate combined with local radiotherapy retarded the tumor growth in nude tumor xenografts; the inhibition produced by 30 mg/kg of artesunate was 74.6%. The results on the possible mechanisms showed artesunate increased the NO level within irradiated A549 cells. Artesunate didn't induce apoptosis of irradiated cells but induced G(2)/M arrest. The induced G(2)/M arrest was related to down-regulated cyclin B1 mRNA expression. Taken together, artesunate exhibited potent radiosensitivity against human A549 cells in vitro and in vivo, probably via NO signal transduction pathway to induce cell cycle arrest at G(2)/M phase. Therefore, artesunate should be further investigated as a radiosensitizer in clinical application.


Dihydroartemisinin improves the efficiency of chemotherapeutics in lung carcinomas in vivo and inhibits murine Lewis lung carcinoma cell line growth in vitro.

forr√°s: http://www.ncbi.nlm.nih.gov/pubmed/19756601


2014-03-11 13:38:18


PURPOSE:

Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has exhibited thestrongest antimalarial activity among the derivatives of artemisinin. There is growingevidence that DHA has some impact against tumors. Our purpose was to evaluate in vitro antitumoral properties of DHA in the murine Lewis lung carcinoma (LLC) cell line. At thesame time, we observed the therapeutic effect of DHA combined with cyclophosphamide(CTX) in the LLC and combined with cisplatin (CDDP) in the human non-small cell lung cancer A549 xenotransplanted carcinoma in vivo.

METHODS:

Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidemethod, apoptosis was measured by AO/EB double staining and flow cytometry. Theexpression of vascular endothelial growth factor (VEGF) receptor KDR/flk-1 was analyzed by western blotting and RT-PCR. In vivo activity of DHA combined with CTX or CDDP wasassayed through tumor growth and metastasis.

RESULTS:

Dihydroartemisinin exhibited high anti-cancer activity in LLC cell line. DHA also inducedapoptosis of LLC cells and influenced the expression of VEGF receptor KDR/flk-1.Furthermore, in both tumor xenografts, a greater degree of growth inhibition was achieved when DHA and chemotherapeutics were used in combination. The affection by DHA combined CTX on LLC tumor metastasis was significant.

CONCLUSIONS:

Dihydroartemisinin is a potent compound against LLC cell line in vitro. In vivo, thecombination strategy of DHA and chemotherapeutics holds promise for the treatment ofrelatively large and rapidly growing lung cancers.


A Hericium erinaceus [szak√°llas s√ľndiszn√≥ gomba, oroszl√°ns√∂r√©ny gomba, majomfej gomba] kivonatban rejlŇĎ r√°kellenes lehetŇĎs√©gek a hum√°n em√©sztŇĎrendszeri r√°kokkal szemben

forr√°s: http://www.ncbi.nlm.nih.gov/pubmed/24631140


2014-04-15 12:36:18


Kivonat

ETNOFARMAKOL√ďGIAI VONATKOZ√ĀS: A Hericium a gomb√°knak (fungus) egy nemzets√©ge a Hericiaceae csal√°dban. A Hericium erinaceus (HE)-t em√©sztŇĎrendszeri betegs√©gek kezel√©s√©re t√∂bb mint 2000 √©ve haszn√°lj√°k K√≠n√°ban. A HE sok olyan j√≥t√©kony hat√°ssal rendelkezik, mint amilyen p√©ld√°ul a r√°kelleness√©g, gyomorfek√©ly-elleness√©g, gyullad√°s g√°tl√°s √©s antimikrobi√°lis hat√°s, immunreakci√≥k befoly√°sol√°sa √©s egy√©b aktivit√°s. A vizsg√°latok c√©lja az volt, hogy √©rt√©kelj√ľk k√©t HE kult√ļra h√ļsleves t√°ptalajb√≥l t√∂rt√©nŇĎ kivonat√°nak (HTJ-5 √©s HTJ-5A) a r√°kkal szembeni hat√©konys√°g√°t h√°rom em√©sztŇĎrendszeri r√°k eset√©ben - mint amilyen a m√°j-, vastagb√©l- √©s gyomorr√°k ‚Äď , mind in vitro sejtvonalakon, mind pedig in vivo tumor xenograftokon (r√°ksejtbe√ľltet√©seken) √©s,  hogy felfedezz√ľk az akt√≠v vegy√ľleteket.

 

ANYAGOK √ČS M√ďDSZEREK: K√©t HE kivonatot (HTJ5 √©s HTJ5A) haszn√°ltunk a vizsg√°latokhoz. A k√©miai √∂sszetevŇĎk tanulm√°nyoz√°s√°hoz a HTJ5-√∂t √©s a HTJ5A-t  makropor√≥zus gyanta √©s szilikon g√©l kombin√°ci√≥j√°t alkalmazva HW 40 √©s LH 20 kromatogr√°fi√°val szepar√°ltuk, azt√°n megtiszt√≠tottuk szemipreparat√≠v, nagy teljes√≠tm√©nyŇĪ folyad√©k kromatogr√°fi√°val (high performance liquid chromatography - HPLC) szepar√°ltuk nukle√°ris m√°gneses rezonancia (NMR) spektrumokkal hat√°roztuk meg. Az in vitro citotoxicit√°si vizsg√°latokhoz HepG2 √©s Huh7 m√°j-, HT-29 vastagb√©l- √©s NCI-87 gyomorr√°k sejtvonalakat haszn√°ltunk √©s MTT pr√≥b√°t [egyfajta kolorimetri√°s pr√≥ba] v√©gezt√ľnk, hogy meghat√°rozzuk az in vitro citotoxicit√°st.

 

Az in vivo r√°kellenes hat√©konys√°gi √©s toxicit√°si vizsg√°latokhoz idegen r√°ksejt be√ľltet√©si modelleket alkalmaztunk s√ļlyos, kombin√°lt immunhi√°nyban (SCID) szenvedŇĎ egerekn√©l, bŇĎr al√° fecskendezve HepG2 √©s HUH-7 m√°jr√°k-, HT-29 vastagb√©lr√°k- √©s NCI-87 gyomorr√°k sejteket. Amikor a daganatok el√©rt√©k a k√∂r√ľlbel√ľl 180-200 mg-ot (mm3), az egereket 5 napon kereszt√ľl naponta sz√°jon √°t adagolt vivŇĎanyaggal, mint kontroll anyaggal, HTJ5-tel √©s HTJ5A-val (500 √©s 1000 mg/kg/nap) kezelt√ľk.  Ezt √∂sszehasonl√≠tottuk az ugyancsak 5 napon √°t naponta has√ľregbe (intraperitone√°lisan) maxim√°lisan toler√°lhat√≥ d√≥zisban (MTD ‚Äď maximum tolerated dose) adagolt ( 25-30 mg/kg/nap) 5-fluorouracil-lal (5-FU,  egy fajta antimetabolit). Ezt k√∂vetŇĎen az elsŇĎ t√≠z napban a daganatok t√©rfogat√°t √©s s√ļly√°t naponta, k√©sŇĎbb hetente 2-3-szor m√©rt√ľk, hogy √©rt√©kelj√ľk a daganatn√∂veked√©s g√°tol√°s√°t, a daganat megkettŇĎzŇĎd√©si idej√©t, a r√©szleges √©s teljes daganat v√°laszt √©s toxicit√°st.

 

EREDM√ČNYEK: A HTJ5/HTJ5A lep√°rl√°sokb√≥l huszonk√©t vegy√ľletet nyert√ľnk, bele√©rtve h√©t ciklikus kettŇĎs feh√©rj√©t, √∂t indolt, pirimidineket, aminosavakat √©s sz√°rmaz√©kaikat, h√°rom flavont, egy antrakinont √©s hat kis arom√°s vegy√ľletet. A HTJ5 √©s a HTJ5A koncentr√°ci√≥t√≥l f√ľggŇĎ citotoxicit√°st mutatott in vitro a  HepG2 √©s Huh-7 m√°jr√°k, a HT-29 vastagb√©l r√°k √©s az NCI-87 gyomorr√°k sejtekkel szemben a maxim√°lis g√°tl√≥ koncentr√°ci√≥ fel√©n√©l (IC50),  vonatkoz√≥an a 2,50¬Ī0,25 √©s a 2,00¬Īo,25; a 0,80¬Ī0,08 √©s az 1,50¬Ī0,28; az  1,25¬Ī0,06 √©s az 1,25¬Ī0,05;  valamint az 5,00¬Ī0,22 √©s 4,50¬Ī0,14 mg/ml-ben. Az in vivo idegen r√°kos sejt be√ľltet√©ses vizsg√°latokban a HTJ5 √©s a HTJ5A jelentŇĎs r√°kellenes hat√©konys√°got mutatott mind a n√©gy -  HepG2, Huh-7, HT-29 √©s NCI-87 -  idegen r√°kos sejt be√ľltet√©ses modell-lel szemben an√©lk√ľl, hogy m√©rgezŇĎ hat√°sa lett volna a gazda√°llatra. Ezen t√ļlmenŇĎen a HTJ5 √©s a HTJ5A kevesebb toxicit√°ssal hat√©konyabb volt a n√©gy r√°kt√≠pussal szemben, mint az 5-Fu.

 

K√ĖVETKEZTET√ČS: A HE kivonatok (HTJ5 √©s HTJ5A) akt√≠vak a HepG2 √©s Huh-7 m√°jr√°k-, a HT-29 vastagb√©lr√°k- √©s az NCI-87 gyomorr√°k sejtekkel szemben in vitro √©s az idegen r√°kos sejtekkel be√ľltetett SCID egerekn√©l in vivo. Mind a n√©gy in vivo daganat modell eset√©ben hat√©konyabbak √©s kev√©sb√© toxikusak az 5-FU-val √∂sszehasonl√≠tva. A vegy√ľletek magukban hordozz√°k annak a lehetŇĎs√©g√©t, hogy √∂n√°ll√≥an √©s/vagy a klinikailag alkalmazott kemoter√°pi√°s gy√≥gyszerekkel egy√ľtt r√°kellenes hat√≥anyagg√° fejlessz√©k ŇĎket. Azonban tov√°bbi vizsg√°latok sz√ľks√©gesek az akt√≠v vegyi √∂sszetevŇĎk megtal√°l√°s√°hoz √©s az erŇĎs in vivo r√°kellenes hat√©konys√°guk hat√°smechanizmus√°nak meg√©rt√©s√©hez. Tov√°bb√°, j√∂vŇĎbeni vizsg√°latok sz√ľks√©gesek ahhoz,  hogy megerŇĎs√≠t√©sre ker√ľljenek azok az elŇĎzetes, az idegen r√°kos sejt bejuttat√°sos √°llat k√≠s√©rletekn√©l kapott eredm√©nyek, ahol in vivo egy√ľtt hat√≥ r√°kellenes hat√©konys√°g mutatkozott,  amikor kombin√°l√°sra ker√ľltek az em√©sztŇĎszervi r√°kfajt√°k kezel√©s√©ben a HE kivonatok √©s az olyan klinikailag alkalmazott r√°kellenes gy√≥gyszerek, mint amilyen az 5-FU, cisplatin √©s a doxurubicin.


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