MyMedR

The effects of NLRP3 inflammasome inhibition by MCC950 on LPS-induced pancreatic adenocarcinoma inflammation

Yaw ACK, Chan EWL, Yap JKY, Mai CW

J Cancer Res Clin Oncol, 2020 Sep;146(9):2219-2229.

PMID: 32507974 DOI: 10.1007/s00432-020-03274-y

PURPOSE: Pancreatic cancer is a lethal form of cancer that can be triggered by prolonged or acute inflammation of the pancreas. Inflammation have been shown to be regulated by a group of key protein molecules known as the inflammasomes. The NLRP3 inflammasome is the most studied inflammasome and have been strongly implicated to regulate cancer cell proliferation. Therefore, this study aimed to examine the regulation of NLRP3 inflammasome under LPS-induced inflammation and its role in modulating cell proliferation in a panel of pancreatic cancer cells.

METHODS: The effects of LPS-induced NLRP3 activation in the presence or absence of MCC950, NLRP3-specific inhibitor, was tested on a panel of three pancreatic cancer cell lines (SW1990, PANC1 and Panc10.05). Western blotting, cell viability kits and ELISA kits were used to examine the effects of LPS-induced NLRP3 activation and inhibition by MCC950 on NLRP3 expression, cell viability, caspase-1 activity and cytokine IL-1β, respectively.

RESULTS: LPS-induced inflammation in the presence of ATP activates NLRP3 that subsequently increases pancreatic cancer cell proliferation by increasing caspase-1 activity leading to overall production of IL-1β. The inhibition of the NLRP3 inflammasome activation via the specific NLRP3 antagonist MCC950 was able to reduce the cell viability of pancreatic cancer cells. However, the efficacy of MCC950 varies between cell types which is most probably due to the difference in ASC expressions which have a different role in inflammasome activation.

CONCLUSION: There is a dynamic interaction between inflammasome that regulates inflammasome-mediated inflammation in pancreatic adenocarcinoma cells.

Matched MeSH terms: Adenocarcinoma/drug therapy*

Modulation of cell growth and PPARgamma expression in human colorectal cancer cell lines by ciglitazone

Yaacob NS, Darus HM, Norazmi MN

Exp. Toxicol. Pathol., 2008 Sep;60(6):505-12.

PMID: 18579355 DOI: 10.1016/j.etp.2008.05.006

Studies have shown that ligand activation of peroxisome proliferator-activated receptor gamma (PPARgamma) can induce differentiation and inhibit proliferation of several cancer cells. The present study was performed to investigate the effects of the PPARgamma ligand, ciglitazone, and the involvement of PPARgamma in modulating the growth of human colorectal cancer cells. Lactate dehydrogenase release assay showed that ciglitazone potently inhibited HT-29 (well-differentiated) and COLO-205 (poorly differentiated) colorectal adenocarcinoma cell growth. Measurement of apoptosis by flow cytometry using a fluorescein-conjugated monoclonal antibody against cytokeratin 18 revealed a high induction of apoptosis by ciglitazone in a time-dependent fashion. The expression of PPARgamma1 but not PPARgamma2 mRNA was significantly downregulated as measured by real-time quantitative PCR, and the PPARgamma protein levels were decreased as determined by Western blot analysis. We conclude that ciglitazone treatment suppressed colon cancer cell growth via induction of apoptosis. However, the anticancer effects of ciglitazone may not depend solely on PPARgamma activation.

Matched MeSH terms: Adenocarcinoma/drug therapy*

Fulltext Induction of apoptosis through oxidative stress-related pathways in MCF-7, human breast cancer cells, by ethyl acetate extract of Dillenia suffruticosa

Tor YS, Yazan LS, Foo JB, Armania N, Cheah YK, Abdullah R, et al.

BMC Complement Altern Med, 2014;14:55.

PMID: 24524627 DOI: 10.1186/1472-6882-14-55

Breast cancer is one of the most dreading types of cancer among women. Herbal medicine has becoming a potential source of treatment for breast cancer. Herbal plant Dillenia suffruticosa (Griff) Martelli under the family Dilleniaceae has been traditionally used to treat cancerous growth. In this study, the anticancer effect of ethyl acetate extract of D. suffruticosa (EADs) was examined on human breast adenocarcinoma cell line MCF-7 and the molecular pathway involved was elucidated.

Matched MeSH terms: Adenocarcinoma/drug therapy*

Fulltext (6E,10E) Isopolycerasoidol and (6E,10E) Isopolycerasoidol Methyl Ester, Prenylated Benzopyran Derivatives from Pseuduvaria monticola Induce Mitochondrial-Mediated Apoptosis in Human Breast Adenocarcinoma Cells

Taha H, Looi CY, Arya A, Wong WF, Yap LF, Hasanpourghadi M, et al.

PLoS One, 2015;10(5):e0126126.

PMID: 25946039 DOI: 10.1371/journal.pone.0126126

Phytochemicals from Pseuduvaria species have been reported to display a wide range of biological activities. In the present study, a known benzopyran derivative, (6E,10E) isopolycerasoidol (1), and a new benzopyran derivative, (6E,10E) isopolycerasoidol methyl ester (2), were isolated from a methanol extract of Pseuduvaria monticola leaves. The structures of the isolated compounds were elucidated by spectroscopic methods including 1D and 2D NMR, IR, UV, and LCMS-QTOF, and by comparison with previously published data. The anti-proliferative and cytotoxic effects of these compounds on human breast cancer cell-lines (MCF-7 and MDA-MB-231) and a human normal breast epithelial cell line (MCF-10A) were investigated. MTT results revealed both (1) and (2) were efficient in reducing cell viability of breast cancer cells. Flow cytometry analysis demonstrated that (1) and (2) induced cell death via apoptosis, as demonstrated by an increase in phosphotidylserine exposure. Both compounds elevated ROS production, leading to reduced mitochondrial membrane potential and increased plasma membrane permeability in breast cancer cells. These effects occurred concomitantly with a dose-dependent activation of caspase 3/7 and 9, a down-regulation of the anti-apoptotic gene BCL2 and the accumulation of p38 MAPK in the nucleus. Taken together, our data demonstrate that (1) and (2) induce intrinsic mitochondrial-mediated apoptosis in human breast cancer cells, which provides the first pharmacological evidence for their future development as anticancer agents.

Matched MeSH terms: Adenocarcinoma/drug therapy*

Mitomycin C adjuvant chemotherapy after Wertheim's hysterectomy for stage IB cervical cancer

Sivanesaratnam V, Jayalakshmi P

Cancer, 1989 Aug 15;64(4):798-800.

PMID: 2501019

Patients undergoing radical surgical treatment for Stage IB and IIA cervical carcinoma are at high risk of developing local recurrence and/or distant metastases when one or more of the following factors are present: presence of metastatic pelvic lymph nodes, a large primary growth, full-thickness tumor invasion of the cervix, clinically undetected parametrial extension, and lymphatic/vascular channel permeation in the cervix by tumor cells. Carcinoma of the cervix appears to be behaving like a systemic disease. Therefore, systemic measures should be considered in its therapy. The authors report the initial experience with the use of mitomycin C as a single agent adjuvant in 16 patients with Stage IB carcinoma of the cervix who had undergone Wertheim radical hysterectomy and were thought to be in this high-risk group. Fourteen of the patients are alive and free of disease after durations of follow-up ranging from 16 to 38 months, the disease-free survival at a median follow-up of 29 months being 87.5%. One patient required discontinuation of adjuvant chemotherapy because of severe marrow toxicity; however, in view of the presence of a multiple risk factors, pelvic irradiation was given instead. She died 13 months later from disseminated disease. A second patient died 6 months later from congestive cardiac failure.

Matched MeSH terms: Adenocarcinoma/drug therapy*

Novel chitosan derivative based composite scaffolds with enhanced angiogenesis; potential candidates for healing chronic non-healing wounds

Rizwan M, Yahya R, Hassan A, Yar M, Abd Halim AA, Rageh Al-Maleki A, et al.

J Mater Sci Mater Med, 2019 Jun 11;30(6):72.

PMID: 31187295 DOI: 10.1007/s10856-019-6273-3

The success of wound healing depends upon the proper growth of vascular system in time in the damaged tissues. Poor blood supply to wounded tissues or tissue engineered grafts leads to the failure of wound healing or rejection of grafts. In present paper, we report the synthesis of novel organosoluble and pro-angiogenic chitosan derivative (CSD) by the reaction of chitosan with 1,3-dimethylbarbituric acid and triethylorthoformate (TEOF). The synthesized material was characterized by FTIR and 13C-NMR to confirm the incorporated functional groups and new covalent connectivities. Biodegradability of the synthesized chitosan derivative was tested in the presence of lysozyme and was found to be comparable with CS. The cytotoxicity and apoptosis effect of new derivative was determined against gastric adenocarcinoma (AGS) cells and was found to be non-toxic. The CSD was found to be soluble in majority of organic solvents. It was blended with polycaprolactone (PCL) to form composite scaffolds. From an ex ovo CAM assay, it was noted that CSD stimulated the angiogenesis.

Matched MeSH terms: Adenocarcinoma/drug therapy

Cytotoxic, apoptotic and anti-α-glucosidase activities of 3,4-di-O-caffeoyl quinic acid, an antioxidant isolated from the polyphenolic-rich extract of Elephantopus mollis Kunth

Ooi KL, Muhammad TS, Tan ML, Sulaiman SF

J Ethnopharmacol, 2011 Jun 1;135(3):685-95.

PMID: 21497647 DOI: 10.1016/j.jep.2011.04.001

The decoction of the whole plant of Elephantopus mollis Kunth. is traditionally consumed to treat various free radical-mediated diseases including cancer and diabetes.

Matched MeSH terms: Adenocarcinoma/drug therapy*

2-Methoxy-1,4-naphthoquinone (MNQ) induces apoptosis of A549 lung adenocarcinoma cells via oxidation-triggered JNK and p38 MAPK signaling pathways

Ong JY, Yong PV, Lim YM, Ho AS

Life Sci, 2015 Aug 15;135:158-64.

PMID: 25896662 DOI: 10.1016/j.lfs.2015.03.019

The compound 2-methoxy-1,4-naphthoquinone (MNQ) was previously shown to be cytotoxic against several cancer cell lines, but its mode of action is poorly understood. In this study, we aimed to explore the molecular mechanism of MNQ-induced cytotoxicity of A549 lung adenocarcinoma cells.

Matched MeSH terms: Adenocarcinoma/drug therapy

Fulltext Cutaneous side-effects of epidermal growth factor receptor-tyrosine kinase inhibitor (TKI) in the treatment of lung cancer: description and its management

Ong CK, Tan WC, Chan LC, Abdul Razak M

Med J Malaysia, 2012 Apr;67(2):222-3.

PMID: 22822651 MyJurnal

Epidermal growth factor receptor (EGFR)--tyrosine kinase inhibitors (TKI) like erlotinib and gefitinib have been approved as monotherapy for the treatment of patients with locally advanced or metastatic non small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen. The use of EGFR-TKI is associated with unique and dramatic dermatologic side effects. We report 2 patients with NSCLC developing a typical acneiform (papulo-pustular) eruption shortly after initiation of EGFR-TKI.

Matched MeSH terms: Adenocarcinoma/drug therapy*

Early salvage hormonal therapy for biochemical failure improved survival in prostate cancer patients after neoadjuvant hormonal therapy plus radiation therapy--a secondary analysis of irish clinical oncology research group 97-01

Mydin AR, Dunne MT, Finn MA, Armstrong JG

Int J Radiat Oncol Biol Phys, 2013 Jan 1;85(1):101-8.

PMID: 22658512 DOI: 10.1016/j.ijrobp.2012.03.001

PURPOSE: To assess the survival benefit of early vs late salvage hormonal therapy (HT), we performed a secondary analysis on patients who developed recurrence from Irish Clinical Oncology Research Group 97-01, a randomized trial comparing 4 vs 8 months neoadjuvant HT plus radiation therapy (RT) in intermediate- and high-risk prostate adenocarcinoma.
METHODS AND MATERIALS: A total of 102 patients from the trial who recurred were analyzed at a median follow-up of 8.5 years. The patients were divided into 3 groups based on the timing of salvage HT: 57 patients had prostate-specific antigen (PSA)≤10 ng/mL and absent distant metastases (group 1, early), 21 patients had PSA>10 ng/mL and absent distant metastases (group 2, late), and 24 patients had distant metastases (group 3, late). The endpoint analyzed was overall survival (OS) calculated from 2 different time points: date of enrolment in the trial (OS1) and date of initiation of salvage HT (OS2). Survival was estimated using Kaplan-Meier curves and a Cox regression model.
RESULTS: The OS1 differed significantly between groups (P

Matched MeSH terms: Adenocarcinoma/drug therapy*

Fulltext Potential activity of fevicordin-A from Phaleria macrocarpa (Scheff) Boerl. seeds as estrogen receptor antagonist based on cytotoxicity and molecular modelling studies

Muchtaridi M, Yusuf M, Diantini A, Choi SB, Al-Najjar BO, Manurung JV, et al.

Int J Mol Sci, 2014 Apr 25;15(5):7225-49.

PMID: 24776765 DOI: 10.3390/ijms15057225

Fevicordin-A (FevA) isolated from Phaleria macrocarpa (Scheff) Boerl. seeds was evaluated for its potential anticancer activity by in vitro and in silico approaches. Cytotoxicity studies indicated that FevA was selective against cell lines of human breast adenocarcinoma (MCF-7) with an IC50 value of 6.4 µM. At 11.2 µM, FevA resulted in 76.8% cell death of T-47D human breast cancer cell lines. Critical pharmacophore features amongst human Estrogen Receptor-α (hERα) antagonists were conserved in FevA with regard to a hypothesis that they could make notable contributions to its pharmacological activity. The binding stability as well as the dynamic behavior of FevA towards the hERα receptor in agonist and antagonist binding sites were probed using molecular dynamics (MD) simulation approach. Analysis of MD simulation suggested that the tail of FevA was accountable for the repulsion of the C-terminal of Helix-11 (H11) in both agonist and antagonist receptor forms. The flexibility of loop-534 indicated the ability to disrupt the hydrogen bond zipper network between H3 and H11 in hERα. In addition, MM/GBSA calculation from the molecular dynamic simulations also revealed a stronger binding affinity of FevA in antagonistic action as compared to that of agonistic action. Collectively, both the experimental and computational results indicated that FevA has potential as a candidate for an anticancer agent, which is worth promoting for further preclinical evaluation.

Matched MeSH terms: Adenocarcinoma/drug therapy*

Synthesis of lantadene analogs with marked in vitro inhibition of lung adenocarcinoma and TNF-α induced nuclear factor-kappa B (NF-κB) activation

Monika, Sharma A, Suthar SK, Aggarwal V, Lee HB, Sharma M

Bioorg Med Chem Lett, 2014 Aug 15;24(16):3814-8.

PMID: 25027934 DOI: 10.1016/j.bmcl.2014.06.068

The new series of pentacyclic triterpenoids reduced lantadene A (3), B (4), and 22β-hydroxy-3-oxo-olean-12-en-28-oic acid (5) analogs were synthesized and tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead analog (11) showed sub-micromolar activity against TNF-α induced activation of NF-κB and exhibited inhibition of IKKβ in a single-digit micromolar dose. At the same time, 11 showed promising cytotoxicity against A549 lung cancer cells with IC50 of 0.98 μM. The Western blot analysis further showed that the suppression of NF-κB activity by the lead analog 11 was due to the inhibition of IκBα degradation, a natural inhibitor of NF-κB. The physicochemical evaluation demonstrated that the lead analog 11 was stable in the simulated gastric fluid of pH 2, while hydrolyzed at a relatively higher rate in the human blood plasma to release the active parent moieties. Molecular docking analysis showed that 11 was hydrogen bonded with the Arg-31 and Gln-110 residues of the IKKβ.

Matched MeSH terms: Adenocarcinoma/drug therapy*

Fulltext Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells

Lim SW, Loh HS, Ting KN, Bradshaw TD, Zeenathul NA

BMC Complement Altern Med, 2014;14:469.

PMID: 25480449 DOI: 10.1186/1472-6882-14-469

Tocotrienols, especially the gamma isomer was discovered to possess cytotoxic effects associated with the induction of apoptosis in numerous cancers. Individual tocotrienol isomers are believed to induce dissimilar apoptotic mechanisms in different cancer types. This study was aimed to compare the cytotoxic potency of alpha-, gamma- and delta-tocotrienols, and to explore their resultant apoptotic mechanisms in human lung adenocarcinoma A549 and glioblastoma U87MG cells which are scarcely researched.

Matched MeSH terms: Adenocarcinoma/drug therapy*

Outcomes of Malaysian patients with advanced lung adenocarcinoma and unknown epidermal growth factor receptor mutation status treated with gefitinib

Liam CK, Ruthranesan M, Lee CH, Pang YK, Chua KT, Lim BK

Asia Pac J Clin Oncol, 2012 Sep;8(3):267-74.

PMID: 22897510 DOI: 10.1111/j.1743-7563.2011.01509.x

To evaluate the response and progression-free survival (PFS) of Malaysian patients with advanced lung adenocarcinoma and unknown epidermal growth factor receptor (EGFR) mutation status treated with gefitinib.

Matched MeSH terms: Adenocarcinoma/drug therapy*

Epidermal growth factor receptor targeted therapy with gefitinib in locally advanced and metastatic primary lung adenocarcinoma

Liam CK, Pang YK, Leow CH

Respirology, 2006 May;11(3):287-91.

PMID: 16635086

To describe the efficacy of monotherapy with the epidermal growth factor receptor-tyrosine kinase inhibitor, gefitinib in patients with locally advanced and metastatic primary lung adenocarcinoma.

Matched MeSH terms: Adenocarcinoma/drug therapy*

Fulltext Alpha-tomatine attenuation of in vivo growth of subcutaneous and orthotopic xenograft tumors of human prostate carcinoma PC-3 cells is accompanied by inactivation of nuclear factor-kappa B signaling

Lee ST, Wong PF, He H, Hooper JD, Mustafa MR

PLoS One, 2013;8(2):e57708.

PMID: 23437404 DOI: 10.1371/journal.pone.0057708

Nuclear factor-kappa B (NF-κB) plays a role in prostate cancer and agents that suppress its activation may inhibit development or progression of this malignancy. Alpha (α)-tomatine is the major saponin present in tomato (Lycopersicon esculentum) and we have previously reported that it suppresses tumor necrosis factor-alpha (TNF-α)-induced nuclear translocation of nuclear factor-kappa B (NF-κB) in androgen-independent prostate cancer PC-3 cells and also potently induces apoptosis of these cells. However, the precise mechanism by which α-tomatine suppresses NF-κB nuclear translocation is yet to be elucidated and the anti-tumor activity of this agent in vivo has not been examined.

Matched MeSH terms: Adenocarcinoma/drug therapy*

Fulltext Preliminary experience with mitomycin, vinblastine and cisplatin (MVP) combination chemotherapy in the treatment of advanced non-small cell lung cancer at University Hospital, Kuala Lumpur

Lee SM

Singapore Med J, 1990 Jun;31(3):228-32.

PMID: 2168091

Twelve patients with advanced inoperable non-small cell lung cancer (NSCLC) were treated with mitomycin, vinblastine and cisplatin (MVP) combination chemotherapy. The overall response rate was 33% (4 partial responses and no complete response) with a median survival of seven months. One responder above subsequently achieved complete remission following successful resection of his tumour and is still alive 14 months after initial chemotherapy. Responses were observed in patients with good performance status and limited disease. Side-effects were generally well tolerated and manageable. MVP is an effective regimen and the low response rate achieved here as compared to other centres is also discussed.

Matched MeSH terms: Adenocarcinoma/drug therapy*

Paronychia induced by the epidermal growth factor receptor inhibitor cetuximab

Lee SL, Tan BS, Chan LC

J Oncol Pharm Pract, 2013 Sep;19(3):273-8.

PMID: 23161875 DOI: 10.1177/1078155212461289

While the development of epidermal growth factor receptor inhibitors has been hailed as a remarkable triumph in the field of oncology, it has inherited with it a host of cutaneous side-effects that have been increasingly observed in a substantial number of patients in the recent years. One cutaneous manifestation that may inflict significant pain and affect activities of daily living among some of the patients receiving epidermal growth factor receptor inhibitors is paronychia. A case of paronychia associated with the use of cetuximab in the management of KRAS wild-type midrectal adenocarcinoma along with its management has been described.

Matched MeSH terms: Adenocarcinoma/drug therapy

Successful pregnancy with epidermal growth factor receptor tyrosine kinase inhibitor treatment of metastatic lung adenocarcinoma presenting with respiratory failure

Lee CH, Liam CK, Pang YK, Chua KT, Lim BK, Lai NL

Lung Cancer, 2011 Nov;74(2):349-51.

PMID: 21920622 DOI: 10.1016/j.lungcan.2011.08.008

We report a woman presenting with respiratory failure due to a right-sided pleural effusion, lung metastases and lymphangitis carcinomatosis from advanced lung adenocarcinoma in the third trimester of pregnancy, who showed good response to EGFR tyrosine kinase inhibitor.

Matched MeSH terms: Adenocarcinoma/drug therapy*

Fulltext Blechnum orientale Linn - a fern with potential as antioxidant, anticancer and antibacterial agent

Lai HY, Lim YY, Kim KH

BMC Complement Altern Med, 2010;10:15.

PMID: 20429956 DOI: 10.1186/1472-6882-10-15

Blechnum orientale Linn. (Blechnaceae) is used ethnomedicinally for the treatment of various skin diseases, stomach pain, urinary bladder complaints and sterilization of women. The aim of the study was to evaluate antioxidant, anticancer and antibacterial activity of five solvent fractions obtained from the methanol extract of the leaves of Blechnum orientale Linn.

Matched MeSH terms: Adenocarcinoma/drug therapy*

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