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  1. Fulltext Cytotoxic, Anti-Proliferative and Apoptosis Activity of l-Amino Acid Oxidase from Malaysian Cryptelytrops purpureomaculatus (CP-LAAO) Venom on Human Colon Cancer Cells
    Zainal Abidin SA, Rajadurai P, Hoque Chowdhury ME, Othman I, Naidu R
    Molecules, 2018 06 08;23(6).
    PMID: 29890640 DOI: 10.3390/molecules23061388
    The aim of this study is to investigate the potential anti-cancer activity of l-amino acid oxidase (CP-LAAO) purified from the venom of Cryptelytrops purpureomaculatus on SW480 and SW620 human colon cancer cells. Mass spectrometry guided purification was able to identify and purify CP-LAAO. Amino acid variations identified from the partial protein sequence of CP-LAAO may suggest novel variants of these proteins. The activity of the purified CP-LAAO was confirmed with o-phenyldiamine (OPD)-based spectrophotometric assay. CP-LAAO demonstrated time- and dose-dependent cytotoxic activity and the EC50 value was determined at 13 µg/mL for both SW480 and SW620 cells. Significant increase of caspase-3 activity, reduction of Bcl-2 levels, as well as morphological changes consistent with apoptosis were demonstrated by CP-LAAO. Overall, these data provide evidence on the potential anti-cancer activity of CP-LAAO from the venom of Malaysian C. purpureomaculatus for therapeutic intervention of human colon cancer.
    Matched MeSH terms: Colonic Neoplasms/pathology*
  2. Differential effects of sPLA2-GV and GX on cellular proliferation and lipid accumulation in HT29 colon cancer cells
    Yap WH, Phang SW, Ahmed N, Lim YM
    Mol Cell Biochem, 2018 Oct;447(1-2):93-101.
    PMID: 29374817 DOI: 10.1007/s11010-018-3295-y
    Secretory phospholipase A2 (sPLA2) group of enzymes have been shown to hydrolyze phospholipids, among which sPLA2 Group V (GV) and Group X (GX) exhibit high selectivity towards phosphatidylcholine-rich cellular plasma membranes. The enzymes have recently emerged as key regulators in lipid droplets formation and it is hypothesized that sPLA2-GV and GX enhanced cell proliferation and lipid droplet accumulation in colon cancer cells (HT29). In this study, cell viability and lipid droplet accumulation were assessed by Resazurin assay and Oil-Red-O staining. Interestingly, both sPLA2-GV and GX enzymes reduced intracellular lipid droplet accumulation and did not significantly affect cell proliferation in HT29 cells. Incubation with varespladib, a pan-inhibitor of sPLA2-Group IIA/V/X, further suppressed lipid droplets accumulation in sPLA2-GV but have no effects in sPLA2-GX-treated cells. Further studies using catalytically inactive sPLA2 enzymes showed that the enzymes intrinsic catalytic activity is required for the net reduction of lipid accumulation. Meanwhile, inhibition of intracellular phospholipases (iPLA2-γ and cPLA2-α) unexpectedly enhanced lipid droplet accumulation in both sPLA2-GV and GX-treated cells. The findings suggested an interconnected relationship between extracellular and intracellular phospholipases in lipid cycling. Previous studies indicated that sPLA2 enzymes are linked to cancer development due to their ability to induce release of arachidonic acid and eicosanoids as well as the stimulation of lipid droplet formation. This study showed that the two enzymes work in a distinct manner and they neither confer proliferative advantage nor enhanced the net lipid droplet accumulation in HT29 cells.
    Matched MeSH terms: Colonic Neoplasms/pathology
  3. Do dysplastic and adenomatous changes in large bowel hamartomas predispose to malignancy?--A report of two cases
    Visvanathan R, Thambidorai CR, Myint H
    Ann Acad Med Singap, 1992 Nov;21(6):830-2.
    PMID: 1338270
    Two patients, members of one family, with Peutz-Jeghers syndrome are described who underwent surgery for bowel obstruction. Both had multiple polyps in the gastrointestinal tract. Severe dysplasia and adenomatous change were present in two hamartomatous polyps adjacent to a stenosing colonic carcinoma in one patient and moderate dysplasia and adenomatous change were observed in two hamartomatous rectal polyps in his son. These changes support recent reports in the literature of progression towards neoplasia in these lesions.
    Matched MeSH terms: Colonic Neoplasms/pathology*
  4. 6-Shogaol inhibits breast and colon cancer cell proliferation through activation of peroxisomal proliferator activated receptor γ (PPARγ)
    Tan BS, Kang O, Mai CW, Tiong KH, Khoo AS, Pichika MR, et al.
    Cancer Lett, 2013 Aug 9;336(1):127-39.
    PMID: 23612072 DOI: 10.1016/j.canlet.2013.04.014
    6-Shogaol has been shown to possess many antitumor properties including inhibition of cancer cell growth, inhibition of cancer metastasis, induction of apoptosis in cancer cells and induction of cancer cell differentiation. Despite its prominent antitumor effects, the direct molecular target of 6-shogaol has remained elusive. To identify the direct targets of 6-shogaol, a comprehensive antitumor profile of 6-shogaol (NSC752389) was tested in the NCI-60 cell line in an in vitro screen. The results show that 6-shogaol is COMPARE negative suggesting that it functions via a mechanism of action distinct from existing classes of therapeutic agents. Further analysis using microarray gene profiling and Connectivity Map analysis showed that MCF-7 cells treated with 6-shogaol display gene expression signatures characteristic of peroxisome proliferator activated receptor γ (PPARγ) agonists, suggesting that 6-shogaol may activate the PPARγ signaling pathway for its antitumor effects. Indeed, treatment of MCF-7 and HT29 cells with 6-shogaol induced PPARγ transcriptional activity, suppressed NFκB activity, and induced apoptosis in breast and colon cancer cells in a PPARγ-dependent manner. Furthermore, 6-shogaol is capable of binding to PPARγ with a binding affinity comparable to 15-delta prostaglandin J2, a natural ligand for PPARγ. Together, our findings suggest that the antitumor effects of 6-shogaol are mediated through activation of PPARγ and imply that activation of PPARγ might be beneficial for breast and colon cancer treatment.
    Matched MeSH terms: Colonic Neoplasms/pathology
  5. Water extract of brewers' rice induces antiproliferation of human colorectal cancer (HT-29) cell lines via the induction of apoptosis
    Tan BL, Norhaizan ME, Yeap SK, Roselina K
    Eur Rev Med Pharmacol Sci, 2015;19(6):1022-9.
    PMID: 25855928
    Brewers' rice, a mixture of broken rice, rice bran, and rice germ, is a rice by-product in the rice industry. The present study was designed to investigate the in vitro cytotoxicity of the water extract of brewers' rice (WBR) against colorectal cancer (HT-29) cells.
    Matched MeSH terms: Colonic Neoplasms/pathology*
  6. Fulltext Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells
    Tahir AA, Sani NF, Murad NA, Makpol S, Ngah WZ, Yusof YA
    Nutr J, 2015;14:31.
    PMID: 25889965 DOI: 10.1186/s12937-015-0015-2
    The interconnected Ras/ERK and PI3K/AKT pathways play a central role in colorectal tumorigenesis, and they are targets for elucidating mechanisms involved in attempts to induce colon cancer cell death. Both ginger (Zingiber officinale) and honey have been shown to exhibit anti-tumor and anti-inflammation properties against many types of cancer, including colorectal cancer. However, there are currently no reports showing the combined effect of these two dietary compounds in cancer growth inhibition. The aim of this study was to evaluate the synergistic effect of crude ginger extract and Gelam honey in combination as potential cancer chemopreventive agents against the colorectal cancer cell line HT29.
    Matched MeSH terms: Colonic Neoplasms/pathology
  7. Cytotoxic effect of fucoidan extracted from Sargassum cinereum on colon cancer cell line HCT-15
    Somasundaram SN, Shanmugam S, Subramanian B, Jaganathan R
    Int J Biol Macromol, 2016 Oct;91:1215-23.
    PMID: 27370748 DOI: 10.1016/j.ijbiomac.2016.06.084
    The present study was aimed to investigate the antioxidant and cytotoxicity activity against HCT-15 of fucoidan from Sargassum cinereum. Purification of fucoidan was done by DEAE cellulose and dialysis. Physicochemical characterization of fucoidan was analysed by calorimetric assay, FT-IR, HPLC and NMR. The extracted fucoidan contains 65.753% of fucose and 3.7±1.54% of sulphate respectively. HPLC results showed that the fucoidan contains the monosaccharide composition such as fucose, galactose, mannose and xylose. Antioxidant effect of fucoidan in Sargassum Cinereum was determined by DPPH. The maximum DPPH activity was found at the concentration of 100μg, where as the crude extract showed the scavenging activity was 63.58±0.56%. Cytotoxicity effect was done by MTT assay. Fucoidan extract caused about 50% of cell death after 24h of incubation with 75±0.9037μg/ml against HCT-15.
    Matched MeSH terms: Colonic Neoplasms/pathology*
  8. Retroperitoneal malignant fibrous histiocytoma causing profuse bleeding per rectum
    Sim PH, Pathmanathan R, Jalleh RP
    Aust N Z J Surg, 1995 Jan;65(1):68-70.
    PMID: 7818432
    A case is reported of retroperitoneal malignant fibrous histiocytoma (MFH) invading into the colon, causing fresh bleeding per rectum. It illustrates the difficulty encountered in the pre-operative diagnosis of this condition, especially in a patient with an atypical presentation of profuse lower gastrointestinal bleeding.
    Matched MeSH terms: Colonic Neoplasms/pathology
  9. Cancer of the colon and rectum in the first three decades of life
    Shahrudin MD, Noori SM
    Hepatogastroenterology, 1997;44(14):441-4.
    PMID: 9164516
    BACKGROUND/AIMS: Recently an increasing number of young colorectal carcinoma patients attending the University Hospital, Kuala Lumpur were noted. This report represents our experience with patients suffering from colorectal cancer aged 30 years or younger.
    MATERIALS AND METHODS: All cases of primary carcinoma of the colon and rectum admitted to the University Hospital during 1990 to 1994 were respectively reviewed. Inclusion criteria was that the patient had been 30 years or younger. Data collected included age, gender, race, site of tumour, presenting symptomatology, duration of symptoms, histology, extension of tumour and nodal involvement predisposing factors, treatment and follow-up.
    RESULTS: 21 patients were included, 5 patients (24%) were 30 years old at diagnosis, 12 (57%) patients were aged 20-29 years and 4 patients (19%) were less than 20 years old. Thirteen of the 21 patients were female, and 8 (38%) were male, 6 of the 21 patients (29%) were Malaysian, while 1 was Indian (4%). The remainder were Chinese, 14 patients (67%). Six patients (29%) had their primary tumour located in the rectosigmoid, 4 (19%) in the left colon, 1 (4%) in the splenic flexure, 2 in the transverse colon (9%), 1 in the hepatic flexure (4%) and 5 in the caecum 24(%). One patient had a tumour too diffuse to detect a primary site at the time of operation. One patient with a family history of polyps had his entire colon removed at age 14. He had 3 separate foci of tumour. The 5-year survival rate was 25%.
    DISCUSSION: Most patients with extensive disease and mucinous histology. Lesions are commonly seen beyond the transverse colon (57%). Presentation included most commonly abdominal pain, haematochezia or haemoccult positive stools.
    CONCLUSION: The symptoms above should alert surgeons to colorectal carcinoma as a differential diagnosis
    Matched MeSH terms: Colonic Neoplasms/pathology
  10. Flat colonic adenomas in Malaysia: fact or fancy?
    Rajendra S, Kutty K, Karim N
    J Gastroenterol Hepatol, 2003 Jun;18(6):701-4.
    PMID: 12753153
    BACKGROUND: Some two-thirds of colorectal carcinomas arise from adenomatous polyps, and as such, screening by colonoscopy and polyp removal should significantly reduce colorectal cancer. This has not been the case, as evidenced by recent studies, which revealed that endoscopy failed to prevent up to 50% of all subsequent carcinomas. Flat or depressed adenomas, frequently reported from Japan but rarely elsewhere, might explain the 'missed carcinomas.' Detection of flat adenomas has not been previously reported from Malaysia.

    METHODS: In the present prospective study, 426 consecutive patients underwent colonoscopic examination between March 1997 and January 2000, for a variety of bowel symptoms. The examinations were performed by an experienced endoscopist using a standard colonoscope and methylene blue dye spraying technique. Macroscopically, flat adenomas were defined using the criteria proposed by Sawada.

    RESULTS: Twenty-nine adenomas were identified in 12 patients, of which 15 were polypoid and 14 were flat, with no depressed lesions. Eight polypoidal lesions and all the flat adenomas contained mild or moderate areas of epithelial dysplasia. Seven severely dysplastic polyps were identified. One Duke's A polypoidal cancer and two advanced carcinomas were also found. All the severely dysplastic lesions and Duke's A carcinomas were found in polyps greater than 10 mm in mean size. The flat adenomas were all less than 5 mm in size.

    CONCLUSIONS: A significant proportion of colonic adenomas in Malaysian patients appear as small flat lesions, which could easily be missed during endoscopy. Increased recognition and treatment of flat adenomas among colonoscopists is warranted.

    Matched MeSH terms: Colonic Neoplasms/pathology
  11. Fulltext Cytotoxicity and Apoptosis Effects of Curcumin Analogue (2E,6E)-2,6-Bis(2,3-Dimethoxybenzylidine) Cyclohexanone (DMCH) on Human Colon Cancer Cells HT29 and SW620 In Vitro
    Rahim NFC, Hussin Y, Aziz MNM, Mohamad NE, Yeap SK, Masarudin MJ, et al.
    Molecules, 2021 Feb 26;26(5).
    PMID: 33652694 DOI: 10.3390/molecules26051261
    Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. According to the Malaysian National Cancer Registry Report 2012-2016, colorectal cancer was the second most common cancer in Malaysia after breast cancer. Recent treatments for colon cancer cases have caused side effects and recurrence in patients. One of the alternative ways to fight cancer is by using natural products. Curcumin is a compound of the rhizomes of Curcuma longa that possesses a broad range of pharmacological activities. Curcumin has been studied for decades but due to its low bioavailability, its usage as a therapeutic agent has been compromised. This has led to the development of a chemically synthesized curcuminoid analogue, (2E,6E)-2,6-bis(2,3-dimethoxybenzylidine) cyclohexanone (DMCH), to overcome the drawbacks. This study aims to examine the potential of DMCH for cytotoxicity, apoptosis induction, and activation of apoptosis-related proteins on the colon cancer cell lines HT29 and SW620. The cytotoxic activity of DMCH was evaluated using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) cell viability assay on both of the cell lines, HT29 and SW620. To determine the mode of cell death, an acridine orange/propidium iodide (AO/PI) assay was conducted, followed by Annexin V/FITC, cell cycle analysis, and JC-1 assay using a flow cytometer. A proteome profiler angiogenesis assay was conducted to determine the protein expression. The inhibitory concentration (IC50) of DMCH in SW620 and HT29 was 7.50 ± 1.19 and 9.80 ± 0.55 µg/mL, respectively. The treated cells displayed morphological features characteristic of apoptosis. The flow cytometry analysis confirmed that DMCH induced apoptosis as shown by an increase in the sub-G0/G1 population and an increase in the early apoptosis and late apoptosis populations compared with untreated cells. A higher number of apoptotic cells were observed on treated SW620 cells as compared to HT29 cells. Human apoptosis proteome profiler analysis revealed upregulation of Bax and Bad proteins and downregulation of Livin proteins in both the HT29 and SW620 cell lines. Collectively, DMCH induced cell death via apoptosis, and the effect was more pronounced on SW620 metastatic colon cancer cells, suggesting its potential effects as an antimetastatic agent targeting colon cancer cells.
    Matched MeSH terms: Colonic Neoplasms/pathology
  12. Fulltext Flavokawain C Inhibits Cell Cycle and Promotes Apoptosis, Associated with Endoplasmic Reticulum Stress and Regulation of MAPKs and Akt Signaling Pathways in HCT 116 Human Colon Carcinoma Cells
    Phang CW, Karsani SA, Sethi G, Abd Malek SN
    PLoS One, 2016;11(2):e0148775.
    PMID: 26859847 DOI: 10.1371/journal.pone.0148775
    Flavokawain C (FKC) is a naturally occurring chalcone which can be found in Kava (Piper methysticum Forst) root. The present study evaluated the effect of FKC on the growth of various human cancer cell lines and the underlying associated mechanisms. FKC showed higher cytotoxic activity against HCT 116 cells in a time- and dose-dependent manner in comparison to other cell lines (MCF-7, HT-29, A549 and CaSki), with minimal toxicity on normal human colon cells. The apoptosis-inducing capability of FKC on HCT 116 cells was evidenced by cell shrinkage, chromatin condensation, DNA fragmentation and increased phosphatidylserine externalization. FKC was found to disrupt mitochondrial membrane potential, resulting in the release of Smac/DIABLO, AIF and cytochrome c into the cytoplasm. Our results also revealed that FKC induced intrinsic and extrinsic apoptosis via upregulation of the levels of pro-apoptotic proteins (Bak) and death receptors (DR5), while downregulation of the levels of anti-apoptotic proteins (XIAP, cIAP-1, c-FlipL, Bcl-xL and survivin), resulting in the activation of caspase-3, -8 and -9 and cleavage of poly(ADP-ribose) polymerase (PARP). FKC was also found to cause endoplasmic reticulum (ER) stress, as suggested by the elevation of GADD153 protein after FKC treatment. After the cells were exposed to FKC (60μM) over 18hrs, there was a substantial increase in the phosphorylation of ERK 1/2. The expression of phosphorylated Akt was also reduced. FKC also caused cell cycle arrest in the S phase in HCT 116 cells in a time- and dose-dependent manner and with accumulation of cells in the sub-G1 phase. This was accompanied by the downregulation of cyclin-dependent kinases (CDK2 and CDK4), consistent with the upregulation of CDK inhibitors (p21Cip1 and p27Kip1), and hypophosphorylation of Rb.
    Matched MeSH terms: Colonic Neoplasms/pathology
  13. Colonic adenosquamous carcinoma and mucinous adenocarcinoma with microsatellite instability
    Parra-Medina R, Lopez-Correa P, Gutierrez V, Polo F
    Malays J Pathol, 2018 Aug;40(2):199-202.
    PMID: 30173239
    A 43-year-old man presented with two-month history of fatigue, weakness, paleness, rectal bleeding, sweating, and weight loss of 10 kg in the past one month. A complete blood count revealed anaemia. The patient underwent a right hemicolectomy. The microscopic examination revealed an adenosquamous carcinoma associated with a mucinous adenocarcinoma in a patient with microsatellite instability due to loss of MLH1 and PMS2 expression and retention of MSH2 and MSH6 expression in both the squamous and glandular components. We also observed an atypical immunohistochemical phenotype in the adenocarcinoma component showing CK7 expression and reduced CK20 and CDX2 expression.
    Matched MeSH terms: Colonic Neoplasms/pathology*
  14. Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NC 6H 4Me-4] for R = Me, Et and iPr, induce apoptosis, cell cycle arrest and inhibit cell invasion of HT-29 colon cancer cells through modulation of the nuclear factor-κB activation pathway and ubiquitination
    Ooi KK, Yeo CI, Ang KP, Akim AM, Cheah YK, Halim SN, et al.
    J Biol Inorg Chem, 2015 Jul;20(5):855-73.
    PMID: 26003312 DOI: 10.1007/s00775-015-1271-5
    The phosphanegold(I) carbonimidothioates, Ph3PAu{SC(OR)=NC6H4Me-4} for R = Me (1), Et (2) and iPr (3), feature linear P-Au-S coordination geometries and exhibit potent in vitro cytotoxicity against HT-29 colon cancer cells in both monolayer and multi-cellular spheroid models (e.g., IC50 = 11.9 ± 0.4 and 20.3 ± 0.3 μM for 2, respectively). Both intrinsic and extrinsic pathways of apoptosis are demonstrated by human apoptosis PCR array analysis, caspase activities, DNA fragmentation and cell apoptotic assays. Compounds 1-3 induce an extrinsic pathway that leads to down-regulation of NFκB. Compound 2 also exhibits an extrinsic apoptotic pathway involving the activation of both p53 and p73, whereas 3 activates p53 only. Lys48- and Lys63-linked polyubiquitination are also promoted by 1-3. Each of cytotoxic Ph3PAu{SC(OR)=NC6H4Me-4}, for R = Me (1), Et (2) and iPr (3), induce an intrinsic apoptotic pathway as well as an extrinsic pathway leading to down-regulation of NFκB. Lys48- and Lys63-linked polyubiquitination are promoted by 1-3 and these are able to inhibit cell invasion and to suppress the activity of TrxR.
    Matched MeSH terms: Colonic Neoplasms/pathology
  15. Fulltext Piper betle leaf extract enhances the cytotoxicity effect of 5-fluorouracil in inhibiting the growth of HT29 and HCT116 colon cancer cells
    Ng PL, Rajab NF, Then SM, Mohd Yusof YA, Wan Ngah WZ, Pin KY, et al.
    J Zhejiang Univ Sci B, 2014 Aug;15(8):692-700.
    PMID: 25091987 DOI: 10.1631/jzus.B1300303
    OBJECTIVE: The combination effect of Piper betle (PB) and 5-fluorouracil (5-FU) in enhancing the cytotoxic potential of 5-FU in inhibiting the growth of colon cancer cells was investigated.
    METHODS: HT29 and HCT116 cells were subjected to 5-FU or PB treatment. 5-FU and PB were then combined and their effects on both cell lines were observed after 24 h of treatment. PB-5-FU interaction was elucidated by isobologram analysis. Apoptosis features of the treated cells were revealed by annexin V/PI stain. High-performance liquid chromatography (HPLC) was performed to exclude any possible chemical interaction between the compounds.
    RESULTS: In the presence of PB extract, the cytotoxicity of 5-FU was observed at a lower dose (IC50 12.5 µmol/L) and a shorter time (24 h) in both cell lines. Both cell lines treated with 5-FU or PB alone induced a greater apoptosis effect compared with the combination treatment. Isobologram analysis indicated that PB and 5-FU interacted synergistically and antagonistically in inhibiting the growth of HT29 and HCT116 cells, respectively.
    CONCLUSIONS: In the presence of PB, a lower dosage of 5-FU is required to achieve the maximum drug effect in inhibiting the growth of HT29 cells. However, PB did not significantly reduce 5-FU dosage in HCT116 cells. Our result showed that this interaction may not solely contribute to the apoptosis pathway.
    KEYWORDS: 5-Fluorouracil; Herb-drug interaction; Isobologram analysis; Piper betle L.; Piperaceae
    Matched MeSH terms: Colonic Neoplasms/pathology
  16. Heterotopic ossification in skeletal muscle metastasis from colonic adenocarcinoma--a case report
    Naik VR, Jaafar H, Mutum SS
    Malays J Pathol, 2005 Dec;27(2):119-21.
    PMID: 17191396
    Colonic adenocarcinoma metastasising to the skeletal muscle is rare. A-56-yr-old Malay man was diagnosed to have adenocarcinoma of the right colon [Dukes B] for which a right hemicolectomy was performed, followed by radiotherapy and chemotherapy. Five years later the patient presented with a mass in the rectus abdominis muscle. The serum carcinoembryonic antigen was 71 ng/Ml. The mass was resected. Gross and microscopical examination showed multiple deposits of mucin-secreting adenocarcinoma with prominent heterotopic ossification in the stroma. The exact pathogenesis and significance of heterotopic ossification is not clear, but bone morphogenetic proteins may play an important role.
    Matched MeSH terms: Colonic Neoplasms/pathology*
  17. Localized giant pseudopolyposis in ulcerative colitis
    Munchar J, Rahman HA, Zawawi MM
    Eur J Gastroenterol Hepatol, 2001 Nov;13(11):1385-7.
    PMID: 11692068
    Localized giant pseudopolyposis is an interesting but unusual manifestation of both ulcerative colitis and Crohn's disease. The purpose of this report is to present a case of localized giant pseudopolyposis complicating an ulcerative colitis, and review other cases reported in the literature. The clinical and pathological findings are described. The authors also discuss the possible aspect of proper management in this type of lesion.
    Matched MeSH terms: Colonic Neoplasms/pathology
  18. Lignans and Polyphenols of Phyllanthus amarus Schumach and Thonn Induce Apoptosis in HCT116 Human Colon Cancer Cells through Caspases-Dependent Pathway
    Mohamed SIA, Jantan I, Nafiah MA, Seyed MA, Chan KM
    Curr Pharm Biotechnol, 2021;22(2):262-273.
    PMID: 32532192 DOI: 10.2174/1389201021666200612173029
    BACKGROUND: The anticancer effects of Phyllanthus amarus extract on various cancer cells have been investigated, however, the effects of its major constituents on HCT116 human colorectal cancer cells have not been reported.

    OBJECTIVE: In the present study, we investigated the cytotoxic effect of 80% ethanol extract of P. amarus and its marker constituents (phyllanthin, hypophyllanthin, gallic acid, niranthin, greraniin, phyltetralin, isolintetralin, corilagin and ellagic acid) on HCT116 and their underlying mechanisms of action.

    METHODS: Their antiproliferative and apoptotic effects on HCT 116 were performed using MTT assay and flow cytometric analysis, respectively, while caspases 3/7, 8 and 9 activities were examined using the colorimetric method. The expression of cleaved poly ADP ribose polymerase enzyme (PARP) and cytochrome c proteins was investigated by the immune-blot technique.

    RESULTS AND DISCUSSION: HPLC and LC-MS/MS analyses demonstrated that the extract contained mainly lignans and polyphenols. The plant samples markedly suppressed the growth and expansion of HCT116 cells in a concentration- and time-dependent manner with no toxicity against normal human fibroblast CCD18 Co. P. amarus extract, phyllanthin and gallic acid induced mode of cell death primarily through apoptosis as confirmed by the exteriorization of phosphatidylserine. Caspases 3/7, 8, and 9 activities increased in a concentration-dependent manner following 24h treatment. The expressions of cleaved PARP (Asp 214) and cytochrome c were markedly upregulated.

    CONCLUSION: P. amarus extract, phyllanthin and gallic acid exhibited an apoptotic effect on HCT116 cells through the caspases-dependent pathway.

    Matched MeSH terms: Colonic Neoplasms/pathology
  19. pH dependent poly[2-(methacryloyloxyethyl)trimetylammonium chloride-co-methacrylic acid]hydrogels for enhanced targeted delivery of 5-fluorouracil in colon cancer cells
    Mishra RK, Ramasamy K, Ahmad NA, Eshak Z, Majeed AB
    J Mater Sci Mater Med, 2014 Apr;25(4):999-1012.
    PMID: 24398912 DOI: 10.1007/s10856-013-5132-x
    Stimuli responsive hydrogels have shown enormous potential as a carrier for targeted drug delivery. In this study we have developed novel pH responsive hydrogels for the delivery of 5-fluorouracil (5-FU) in order to alleviate its antitumor activity while reducing its toxicity. We used 2-(methacryloyloxyethyl) trimetylammonium chloride a positively charged monomer and methacrylic acid for fabricating the pH responsive hydrogels. The released 5-FU from all except hydrogel (GEL-5) remained biologically active against human colon cancer cell lines [HT29 (IC50 = 110-190 μg ml(-1)) and HCT116 (IC50 = 210-390 μg ml(-1))] but not human skin fibroblast cells [BJ (CRL2522); IC50 ≥ 1000 μg ml(-1)]. This implies that the copolymer hydrogels (1-4) were able to release 5-FU effectively to colon cancer cells but not normal human skin fibroblast cells. This is probably due to the shorter doubling time that results in reduced pH in colon cancer cells when compared to fibroblast cells. These pH sensitive hydrogels showed well defined cell apoptosis in HCT116 cells through series of events such as chromatin condensation, membrane blebbing, and formation of apoptotic bodies. No cell killing was observed in the case of blank hydrogels. The results showed the potential of these stimuli responsive polymer hydrogels as a carrier for colon cancer delivery.
    Matched MeSH terms: Colonic Neoplasms/pathology
  20. Bioengineered silver nanoparticles capped with bovine serum albumin and its anticancer and apoptotic activity against breast, bone and intestinal colon cancer cell lines
    Majeed S, Aripin FHB, Shoeb NSB, Danish M, Ibrahim MNM, Hashim R
    Mater Sci Eng C Mater Biol Appl, 2019 Sep;102:254-263.
    PMID: 31146998 DOI: 10.1016/j.msec.2019.04.041
    The aim of the current study was to biosynthesize the silver nanoparticles (AgNPs) from the bacterial strain of Bacillus cereus (ATCC 14579) extracellularly. When bacterial extract was challenged with 1 mM silver nitrate (AgNO3) the color of the extract changed into brown confirms the formation of nanoparticles. These nanoparticles were capped with bovine serum albumin (BSA). UV- visible spectroscopy showed the absorption peak at 420 nm indicates the formation of AgNPs. Fourier Infra -red (FTIR) attenuated total reflection (ATR) spectroscopy showed amide and amine group associated with AgNPs that stabilizes the nanoparticles. Energy dispersive x-ray spectroscopy (EDX) showed a strong peak of silver confirms the presence of silver. Thermo gravimetric analysis (TGA) analysis was used to determine the protein degradation showed less protein degradation at higher temperature confirms the stability of nanoparticles. Transmission electron microscopy (TEM) showed the AgNPs are well dispersed and spherical, and 5.37 nm to 17.19 whereas albumin coated nanoparticles are size ranges from 11.26 nm to 23.85 nm. The anticancer effect of capped AgNPs (cAgNPs) showed the IC50 value against breast cancer MCF-7 at 80 μg/mL, intestinal colon cancer HCT- 116 60 μg/mL, and bone cancer osteosarcoma MG-63 cell line80 μg/mL while against normal fibroblast cells 3T3 cells showed the IC50 value at 140 μg/mL. Lactate dehydrogenase assay (LDH) showed higher toxicity on MCF-7, HCT-116, and MG-63 cells. The apoptotic study clearly showed the blebbing of membrane, chromatin condensation due to the production of reactive oxygen species (ROS) by ethidium bromide and acridine orange dual staining method. The DNA analysis showed the complete fragmentation of the DNA of treated cells when compared with control cells.
    Matched MeSH terms: Colonic Neoplasms/pathology
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