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P16INK4a: a potential diagnostic adjunct for prediction of high-grade cervical lesions in liquid-based cytology: with HPV testing and histological correlation

Wong YP, Abdul Raub SH, Mohd Dali AZ, Kassim F, Visvalingam V, Zakaria Z, et al.

Malays J Pathol, 2016 Aug;38(2):93-101.
PMID: 27568665

Human papillomavirus (HPV) is a necessary cause of cervical cancer and its precursors. Increased expression of high-risk hrHPV viral oncogenes in abnormal cells might increase the expression of p16INK4a. We aimed to determine the role of p16INK4a in detecting hrHPV-transformed epithelial cells in liquid-based cervical cytology, and compared the results with hrHPV DNA testing by realtime polymerase chain reaction (RT-PCR). Fifty-seven cytological samples were tested for p16INK4a immunomarker and hrHPV DNA. Test performance of both tests was determined by comparing sensitivity, specificity and predictive values using available histological follow-up data as gold standard. Of 57 samples, 36 (63.2%) showed immunoreactivity for p16INK4a and 43 (75.4%) were hrHPV-infected. A fairly low concordance rate (k = 0.504) between p16INK4a immunolabelling and hrHPV DNA status was noted. For prediction of cervical intraepithelial neoplasia (CIN) II and worse lesions, p16INK4a had a sensitivity and specificity of 93.5% and 60%; whereas hrHPV DNA testing had a sensitivity and specificity of 100% and 20%. Dual testing by combining p16INK4a and hrHPV showed sensitivity and specificity of 100% and 33.3%. In conclusion, p16INK4a is useful in predicting severity of the cytological abnormalities. Although p16INK4a is more specific but less sensitive than hrHPV in detecting high-grade cervical lesions, a combination of both tests failed to demonstrate significant improvement in diagnostic sensitivity, specificity and predictive value. Larger-scale prospective studies are required to assess further whether this biomarker should be routinely used as primary screening tool independently or in combination with hrHPV testing to improve diagnostic accuracy in cervical cytology.

Matched MeSH terms: Adenocarcinoma/diagnosis*; Adenocarcinoma/virology
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*; Adenocarcinoma/enzymology; Adenocarcinoma/genetics
Oral 5-fluorouracil colon-specific delivery through in vivo pellet coating for colon cancer and aberrant crypt foci treatment

Bose A, Elyagoby A, Wong TW

Int J Pharm, 2014 Jul 1;468(1-2):178-86.
PMID: 24709212 DOI: 10.1016/j.ijpharm.2014.04.006

In situ coating of 5-fluorouracil pellets by ethylcellulose and pectin powder mixture (8:3 weight ratio) in capsule at simulated gastrointestinal media provides colon-specific drug release in vitro. This study probes into pharmacodynamic and pharmacokinetic profiles of intra-capsular pellets coated in vivo in rats with reference to their site-specific drug release outcomes. The pellets were prepared by extrusion-spheronization technique. In vitro drug content, drug release, in vivo pharmacokinetics, local colonic drug content, tumor, aberrant crypt foci, systemic hematology and clinical chemistry profiles of coated and uncoated pellets were examined against unprocessed drug. In vivo pellet coating led to reduced drug bioavailability and enhanced drug accumulation at colon (179.13 μg 5-FU/g rat colon content vs 4.66 μg/g of conventional in vitro film-coated pellets at 15 mg/kg dose). The in vivo coated pellets reduced tumor number and size, through reforming tubular epithelium with basement membrane and restricting expression of cancer from adenoma to adenocarcinoma. Unlike uncoated pellets and unprocessed drug, the coated pellets eliminated aberrant crypt foci which represented a putative preneoplastic lesion in colon cancer. They did not inflict additional systemic toxicity. In vivo pellet coating to orally target 5-fluorouracil delivery at cancerous colon is a feasible therapeutic treatment approach.

Matched MeSH terms: Adenocarcinoma/chemically induced; Adenocarcinoma/drug therapy*; Adenocarcinoma/metabolism; Adenocarcinoma/pathology
Opposing trends in incidence of esophageal squamous cell carcinoma and adenocarcinoma in a multi-ethnic Asian country

Fernandes ML, Seow A, Chan YH, Ho KY

Am J Gastroenterol, 2006 Jul;101(7):1430-6.
PMID: 16863543

To describe the incidence trends in esophageal squamous cell carcinoma (SCC) and adenocarcinoma among the three major ethnic groups in Singapore from 1968 to 2002.

Matched MeSH terms: Adenocarcinoma/ethnology*; Adenocarcinoma/epidemiology
One patient, two lymphomas, three primaries

Eshra A, Al-Hendal A, Al Enezi M, Al-Mishaan M, Abo Dief W

Gulf J Oncolog, 2010 Jul.
PMID: 20601338

Concomitant adenocarcinoma and non-Hodgkin's lymphoma, both located in the intestinal tract, are unusual. Collision tumors of the colon on the other hand are extremely rare neoplasms. A case of true collision tumor of a marginal zone lymphoma and a moderately differentiated adenocarcinoma of the ascending colon (hepatic flexure) is reported. Simultaneously, a third primary is identified as follicular lymphoma involving the terminal ileum. Correlation with clinical history, radiology investigations, endoscopic findings and histological examination of the resected specimen as well as the use of ancillary techniques such as immunohistochemistry are the most useful in making the correct diagnosis of a synchronous three primaries involving the small bowel and colon. Therefore, we present these three primary synchronous neoplasms involving two different parts of the gastrointestinal tract, with two of these three primaries colliding at one organ.

Matched MeSH terms: Adenocarcinoma/pathology*
Oesophageal hepatoid carcinoma with liver metastasis, a diagnostic dilemma

Yahaya A, Wa Kammal WS, Abd Shukor N, Osman SS

Malays J Pathol, 2019 Apr;41(1):59-63.
PMID: 31025640

Alpha-fetoprotein (AFP)-producing carcinoma which microscopically mimics hepatocellular carcinoma (HCC) is a rare entity known as hepatoid adenocarcinoma (HC). They usually arise in the stomach, while oesophageal origin is only occasionally encountered. This tumour is highly aggressive and is associated with a poor prognosis. They frequently metastasise to the liver, thus giving rise to diagnostic difficulty, especially in cases where simultaneous oesophageal and liver mass are present. We reported a case of oesophageal hepatoid carcinoma with multiple liver metastasis, that was associated with an increased serum AFP. The distinction between HCC and HC is important because HC is more aggressive and has a poorer prognosis with limited therapeutic options. An extensive diagnostic work-up which include a thorough clinical history, radiological investigations (computed tomography or magnetic resonance imaging) as well as tissue biopsy supported by a panel of immunohistochemical markers are necessary to aid in the diagnosis of HC.

Matched MeSH terms: Adenocarcinoma
Nucleolar organizer regions distribution in fine needle aspiration cytological smears from breast lesions

Hasnan J, Jayaram G

Malays J Pathol, 1996 Jun;18(1):35-41.
PMID: 10879223

Fine needle aspiration (FNA) cytology is now an integral part of the pre-operative investigation of breast lesions and the therapeutic protocol is today often planned on the basis of cytodiagnosis. However, from time to time the cytological picture may be equivocal or inconclusive. In recent years, nucleolar organizer region (NOR) scores have been explored for potential value in the diagnosis of malignancy as the scores in malignant nuclei are seen to be higher than in benign or reactive nuclei. With a view to applying NOR scoring in the evaluation of cytologically equivocal cases, we adopted the argyrophil technique for staining NOR s (AgNOR) in FNA cytological smears of 56 breast lesions, comprising 31 benign and 25 malignant lesions. Histological correlation was possible in 26 of these cases (17 malignant and 9 benign) and AgNOR scoring was done on paraffin sections of these as well. There was a significant difference between mean AgNOR scores in benign and malignant lesions in the cytological smears (P < 0.001). The AgNOR scores ranged from 2.5 to 5.0 per cell in benign lesions and 5.8 to 17.2 per cell in malignant lesions. None of the cases fell into the gray zone of overlap. One malignant lesion that was cytologically equivocal showed a mean AgNOR score of 6.08. The AgNOR scores on histological sections also showed a statistically significant difference (P < 0.001) between benign and malignant lesions with mean scores ranging from 1.34 to 2.58 dots per cell in benign lesions and scores of 2.42 to 5.28 dots per cell in malignant lesions. However, the scores overlapped in four cases and therefore it was considered unsuitable for routine diagnostic work. From this preliminary study, we conclude that an FNA AgNOR score of 5.0 and less strongly favours a benign lesion whereas a score above 5.0 would be in favour of a malignant lesion. A larger study would be needed to verify our impression that AgNOR scoring can be useful in cytologically equivocal cases.

Matched MeSH terms: Adenocarcinoma/pathology
Nuclear morphometry and texture analysis on cytological smears of thyroid neoplasms: a study of 50 cases

Deka L, Gupta S, Gupta R, Gupta K, Kaur CJ, Singh S S

Malays J Pathol, 2017 Apr;39(1):33-37.
PMID: 28413203

BACKGROUND: Fine needle aspiration cytology (FNAC) is a reliable and reproducible diagnostic technique for thyroid lesions with certain limitations. Computed morphometric methods have been introduced with a view to improve the diagnostic yield of thyroid aspirates. However, a review of the existing literature revealed conflicting reports regarding morphometric parameters in thyroid neoplasms.
MATERIALS AND METHODS: This study included 50 cases of thyroid lesions (20 cases of colloid goitre, 15 of follicular adenoma, 5 of follicular carcinoma and 10 papillary carcinomas). Digital images of cytologic smears of these cases were captured using a dedicated photomicrography system and nuclear profiles traced manually. With self-designed image analysis software, nuclear morphometric measurements, including texture analysis, were performed. Discriminant analysis was performed including the morphometric parameters and percentage of correctly classified nuclei noted.
RESULTS: Nuclear morphometry parameters showed that papillary thyroid carcinoma had the highest perimeter, area, radius and elongation factor compared to other thyroid lesions. Discriminant analysis revealed that altogether 77.9% of cells could be correctly classified to their lesion category based on the nuclear morphometric and textural parameters. Of the neoplastic cases, 84.5% of cells of follicular neoplasms and 72.5% of papillary carcinoma were classified to the respective category.
CONCLUSION: Nuclear morphometry, including texture analysis, can assist in the cytologic diagnosis of thyroid lesions, considering the high degree of accuracy of classification. Further studies and methodological refinements can achieve higher accuracy.

Matched MeSH terms: Adenocarcinoma, Follicular/diagnosis*; Adenocarcinoma, Follicular/pathology
Novel lung adenocarcinoma and nuclear factor-kappa B (NF-κB) inhibitors: synthesis and evaluation of lantadene congeners

Suthar SK, Boon HL, Sharma M

Eur J Med Chem, 2014 Mar 3;74:135-44.
PMID: 24457265 DOI: 10.1016/j.ejmech.2013.12.052

The C-3, C-17 and C-22 congeners of pentacyclic triterpenoids reduced lantadene A (3), B (4) and 22β-hydroxyoleanolic acid (5) were synthesized and were tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead congeners 12 and 13 showed IC50 of 0.56 and 0.42 μmol, respectively against TNF-α induced activation of NF-κB. The congeners 12 and 13 exhibited inhibition of IKKβ in a single-digit micromolar dose and at the same time, 12 and 13 showed marked cytotoxicity against A549 lung cancer cells with IC50 of 0.12 and 0.08 μmol, respectively. The lead ester congeners were stable in the acidic pH, while hydrolyzed readily in the human blood plasma to release the active parent moieties.

Matched MeSH terms: Adenocarcinoma/metabolism; Adenocarcinoma/pathology*
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
Fulltext Nontoxic Glucomoringin-Isothiocyanate (GMG-ITC) Rich Soluble Extract Induces Apoptosis and Inhibits Proliferation of Human Prostate Adenocarcinoma Cells (PC-3)

Jaafaru MS, Abd Karim NA, Mohamed Eliaser E, Maitalata Waziri P, Ahmed H, Mustapha Barau M, et al.

Nutrients, 2018 Aug 27;10(9).
PMID: 30150582 DOI: 10.3390/nu10091174

The incidence of prostate cancer malignancy along with other cancer types is increasing worldwide, resulting in high mortality rate due to lack of effective medications. Moringa oleifera has been used for the treatment of communicable and non-communicable ailments across tropical countries, yet, little has been documented regarding its effect on prostate cancer. We evaluated the acute toxicity and apoptosis inducing effect of glucomoringin-isothiocyanate rich soluble extracts (GMG-ITC-RSE) from M. oleifera in vivo and in vitro, respectively. Glucomoringin was isolated, identified, and characterized using fundamental analytical chemistry tools where Sprague-Dawley (SD) rats, murine fibroblast (3T3), and human prostate adenocarcinoma cells (PC-3) were used for acute toxicity and bioassays experiments. GMG-ITC-RSE did not instigate adverse toxic reactions to the animals even at high doses (2000 mg/kg body weight) and affected none of the vital organs in the rats. The extract exhibited high levels of safety in 3T3 cells, where more than 90% of the cells appeared viable when treated with the extract in a time-dependent manner even at high dose (250 µg/mL). GMG-ITC-RSE significantly triggered morphological aberrations distinctive to apoptosis observed under microscope. These findings obviously revealed the putative safety of GMG-ITC-RSE in vivo and in vitro, in addition to its anti-proliferative effect on PC-3 cells.

Matched MeSH terms: Adenocarcinoma/drug therapy*; Adenocarcinoma/pathology
Mutations in mitochondrial NADH dehydrogenase subunit 1 (mtND1) gene in colorectal carcinoma

Yusnita Y, Norsiah MD, Rahman AJ

Malays J Pathol, 2010 Dec;32(2):103-10.
PMID: 21329181 MyJurnal

Mitochondrial Subunit ND1 (mtND1) gene is involved in the first step of the electron transport chain of oxidative phosphorylation (OXPHOS). Alteration of the electron transport components by mutations in mtDNA may compromise the normal electron flow. This could lead to an increase of bifurcation and generation of superoxidase radicals and increase oxidative stress in various types of cancer cells. Genomic DNA was extracted from thirty matched primary colorectal tumour tissues and matching non-tumour tissues. Blood samples were obtained from twenty-five normal people. The mtNDI coding region was amplified by step-down PCR. The purified products were then subjected to direct sequencing and subsequently, the DNA sequences obtained were compared with the revised Cambridge Reference Sequence (rCRS) and MITOMAP. From the analysis, the mtND1 gene showed 11 (45.8%) different mutations and also 13 (54.2%) polymorphisms. The heteroplasmic mutation A4123A/G (I273I/V) might have a pathogenic significance as it fulfills various pathogenic criteria. Three mutations, T3394C (Y30H), A3434G (Y43C) and C3497T (A64V) which occur in a highly conserved region were likely to alter the structure and function of the ND1 protein. We suggest that these mutations, and in combination with the polymorphic variance in mtDNA, may cause slight changes that generate subtly higher levels of toxic reactive oxygen species (ROS).

Matched MeSH terms: Adenocarcinoma/genetics*
Fulltext Multiple Genome Sequences of Helicobacter pylori Strains of Diverse Disease and Antibiotic Resistance Backgrounds from Malaysia

Rehvathy V, Tan MH, Gunaletchumy SP, Teh X, Wang S, Baybayan P, et al.

Genome Announc, 2013;1(5).
PMID: 24051312 DOI: 10.1128/genomeA.00687-13

Helicobacter pylori causes human gastroduodenal diseases, including chronic gastritis and peptic ulcer disease. It is also a major microbial risk factor for the development of gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. Twenty-one strains with different ethnicity, disease, and antimicrobial susceptibility backgrounds were sequenced by use of Illumina HiSeq and PacBio RS platforms.

Matched MeSH terms: Adenocarcinoma
Multifocal mucus secreting papillary adenocarcinoma of the bile duct causing obstructive jaundice

Khan TF, Sherazi ZA, Alias NA, Mahmood Z

Ann Acad Med Singap, 1993 Mar;22(2):251-3.
PMID: 8363342

We present a 64-year-old Malay lady who had undergone a choledochoduodenostomy (CDD) two years ago for obstructive jaundice. She was admitted with jaundice and underwent ultrasonography, percutaneous transhepatic cholangiography (PTC), endoscopic retrograde cholangio pancreatography (ERCP) and computed tomographic (CT) scanning of the liver and biliary tree. All the investigations confirmed a type IVa choledochal cyst. At operation, the grossly dilated biliary system was packed with a thick mucoid material and the mucosa of the bile ducts was visibly abnormal with scattered nodules. This mucoid material had caused occlusion of the entire biliary tree resulting in obstructive jaundice. To the best of our knowledge, this is probably the first report of obstructive jaundice caused by thick mucus. The peculiar management problems of this case and the risk of malignant change in choledochal cysts are discussed.

Matched MeSH terms: Adenocarcinoma, Papillary/complications*; Adenocarcinoma, Papillary/diagnosis; Adenocarcinoma, Papillary/metabolism; Adenocarcinoma, Papillary/pathology; Adenocarcinoma, Papillary/surgery
Mucinous carcinoma (colloid carcinoma) of the lung diagnosed by fine needle aspiration cytology: a case report

Jayaram G, Yaccob R, Liam CK

Malays J Pathol, 2003 Jun;25(1):63-8.
PMID: 16196380

Mucinous carcinoma of the lung, also known as colloid carcinoma, is an uncommon tumour that is rarely encountered in fine needle aspiration (FNA) cytological practice. A 64-year-old Chinese male presenting with blood stained sputum and hoarseness of voice was discovered to have a 3 cm sized mass in the left lung. Neither bronchial washings nor transthoracic FNA yielded positive results at this stage. Six months later the patient returned to the hospital with a larger tumour and mediastinal lymphadenopathy. Transbronchial lymph node FNA, reported as negative for malignancy showed normal, hyperplastic and mildly atypical bronchial epithelial cells as well as a few single cells and extracellular mucin. Transthoracic FNA of the lung lesion performed under computed tomographic guidance showed characteristic cytological features of this tumour, establishing the diagnosis.

Matched MeSH terms: Adenocarcinoma, Mucinous/pathology*; Adenocarcinoma, Mucinous/surgery
Fulltext Mucinous adenocarcinoma of the renal pelvis associated with lithiasis and chronic gout

Kaur G, Naik VR, Rahman MNG

Singapore Med J, 2004 Mar;45(3):125-6.
PMID: 15029415

Diffusely-infiltrating mucinous adenocarcinoma of the renal pelvis associated with lithiasis and chronic gout is reported in a 61-year-old Malay man. The patient underwent left nephrectomy and vesiculo-lithotomy. This tumour is postulated to arise in response to chronic irritation of the urothelium.

Matched MeSH terms: Adenocarcinoma, Mucinous/etiology*; Adenocarcinoma, Mucinous/pathology*; Adenocarcinoma, Mucinous/surgery
Fulltext Mucinous adenocarcinoma of the rectum with breast and ocular metastases

Hisham RB, Thuaibah H, Gul YA

Asian J Surg, 2006 Apr;29(2):95-7.
PMID: 16644510

We present the case of a 32-year-old woman who, 10 months after abdominoperineal resection and total mesorectal excision for a locally advanced mucinous adenocarcinoma of the rectum, presented with local recurrence and metastases to the breast, spine, the left eye and orbit. Following surgery, due to the patient's personal reasons, adjuvant chemoradiation was not given. The patient died 2 months later, with disseminated cancer. To the best of our knowledge, breast as well as ocular metastasis in a patient with mucinous adenocarcinoma of the rectum has never been reported and, therefore, needs to be documented.

Matched MeSH terms: Adenocarcinoma, Mucinous/pathology*
Fulltext Mucinous adenocarcinoma arising from chronic perianal fistula

Hisham RB, Sabariah AR, Yunus AG

Med J Malaysia, 2006 Mar;61(1):88-90.
PMID: 16708740 MyJurnal

Perianal mucinous adenocarcinoma is a rare tumor which may be associated with long-standing chronic perianal sepsis. Early diagnosis is challenging and is based on a high index of clinical suspicion and specific histological features. Definitive treatment is surgical, in the form of an abdomino-perineal resection. We hereby describe a case of a perianal mucinous adenocarcinoma arising from long-standing recurrent perianal fistula and complement this with a brief review of the literature pertaining in particular to the management of this condition.

Matched MeSH terms: Adenocarcinoma, Mucinous/diagnosis*; Adenocarcinoma, Mucinous/etiology
Morphological and biochemical changes of andrographolide-induced cell death in human prostatic adenocarcinoma PC-3 cells

Kim TG, Hwi KK, Hung CS

In Vivo, 2005 May-Jun;19(3):551-7.
PMID: 15875775

Andrographolide was extracted and purified from Andrographis panicula using hexane and water partitioning followed by ethyl acetate extraction and chromatography. It showed selective cytotoxicity to prostate cancer PC-3 cells in vitro. The morphological and biochemical changes induced by the extract in carcinoma PC-3 cell death were studied. In andrographolide-treated cells, evidence of apoptosis such as cell shrinkage and surface microvilli loss after 4-hour treatment and chromatin condensation and fragmentation in H&E-stained cells between 4 to 8 hours after treatment were observed. Under electron microscopy, membrane blebbing and apoptotic bodies formation were seen after 8-hour treatment. Using immunocytochemistry staining and cellular caspase-3 activity assay, andrographolide-treated cells showed considerable caspase-3 activation and caspase-8 in PC-3 cells at 4 and 2 hours after treatment, respectively. This suggests andrographolide-induced cell death was achieved through the apoptotic pathway, via the activation of an extrinsic caspase cascade.

Matched MeSH terms: Adenocarcinoma/metabolism; Adenocarcinoma/pathology*
Molecular mechanisms of apoptosis and cell selectivity of zinc dithiocarbamates functionalized with hydroxyethyl substituents

Tan YS, Ooi KK, Ang KP, Akim AM, Cheah YK, Halim SN, et al.

J Inorg Biochem, 2015 Sep;150:48-62.
PMID: 26086852 DOI: 10.1016/j.jinorgbio.2015.06.009

In the solid state each of three binuclear zinc dithiocarbamates bearing hydroxyethyl groups, {Zn[S2CN(R)CH2CH2OH]2}2 for R = iPr (1), CH2CH2OH (2), and Me (3), and an all alkyl species, [Zn(S2CNEt2)2]2 (4), features a centrosymmetric {ZnSCS}2 core with a step topology; both 1 and 3 were isolated as monohydrates. All compounds were broadly cytotoxic, specifically against human cancer cell lines compared with normal cells, with greater potency than cisplatin. Notably, some selectivity were indicated with 2 being the most potent against human ovarian carcinoma cells (cisA2780), and 4 being more cytotoxic toward multidrug resistant human breast carcinoma cells (MCF-7R), human colon adenocarcinoma cells (HT-29), and human lung adenocarcinoma epithelial cells (A549). Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis in HT-29 cells is demonstrated via both extrinsic and intrinsic pathways. Compounds 2-4 activate the p53 gene while 1 activates both p53 and p73. Cell cycle arrest at the S and G2/M phases correlates with inhibition of HT-29 cell growth. Cell invasion is also inhibited by 1-4 which is correlated with down-regulation of NF-κB.

Matched MeSH terms: Adenocarcinoma

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