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Displaying publications 41 - 46 of 46 in total

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BZD9L1 sirtuin inhibitor: Identification of key molecular targets and their biological functions in HCT 116 colorectal cancer cells

Tan YJ, Lee YT, Mancera RL, Oon CE

Life Sci, 2021 Nov 01;284:119747.
PMID: 34171380 DOI: 10.1016/j.lfs.2021.119747

BZD9L1 was previously described as a SIRT1/2 inhibitor with anti-cancer activities in colorectal cancer (CRC), either as a standalone chemotherapy or in combination with 5-fluorouracil. BZD9L1 was reported to induce apoptosis in CRC cells; however, the network of intracellular pathways and crosstalk between molecular players mediated by BZD9L1 is not fully understood. This study aimed to uncover the mechanisms involved in BZD9L1-mediated cytotoxicity based on previous and new findings for the prediction and identification of related pathways and key molecular players. BZD9L1-regulated candidate targets (RCTs) were identified using a range of molecular, cell-based and biochemical techniques on the HCT 116 cell line. BZD9L1 regulated major cancer pathways including Notch, p53, cell cycle, NFκB, Myc/MAX, and MAPK/ERK signalling pathways. BZD9L1 also induced reactive oxygen species (ROS), regulated apoptosis-related proteins, and altered cell polarity and adhesion profiles. In silico analyses revealed that most RCTs were interconnected, and were involved in the modulation of catalytic activity, metabolism and transcription regulation, response to cytokines, and apoptosis signalling pathways. These RCTs were implicated in p53-dependent apoptosis pathway. This study provides the first assessment of possible associations of molecular players underlying the cytotoxic activity of BZD9L1, and establishes the links between RCTs and apoptosis through the p53 pathway.

Matched MeSH terms: Colorectal Neoplasms/metabolism
Koetjapic acid, a natural triterpenoid, induces apoptosis in colon cancer cells

Nassar ZD, Aisha AF, Idris N, Khadeer Ahamed MB, Ismail Z, Abu-Salah KM, et al.

Oncol Rep, 2012 Mar;27(3):727-33.
PMID: 22134768 DOI: 10.3892/or.2011.1569

Deregulated cell signaling pathways result in cancer development. More than one signal transduction pathway is involved in colorectal cancer pathogenesis and progression. Koetjapic acid (KA) is a naturally occurring seco-A-ring oleanene triterpene isolated from the Sandoricum koetjape stem bark. We report the cellular and molecular mechanisms of anticancer activity of KA towards human colorectal cancer. The results showed that KA induces apoptosis in HCT 116 colorectal carcinoma cells by inducing the activation of extrinsic and intrinsic caspases. We confirmed that KA-induced apoptosis was mediated by DNA fragmentation, nuclear condensation and disruption in the mitochondrial membrane potential. Further studies on the effect of KA on cancer pathways show that the compound causes down-regulation of Wnt, HIF-1α, MAP/ERK/JNK and Myc/Max signaling pathways and up-regulates the NF-κB signaling pathway. The result of this study highlights the anticancer potential of KA against colorectal cancer.

Matched MeSH terms: Colorectal Neoplasms/metabolism
Fulltext Chemopreventive evaluation of a Schiff base derived copper (II) complex against azoxymethane-induced colorectal cancer in rats

Hajrezaie M, Hassandarvish P, Moghadamtousi SZ, Gwaram NS, Golbabapour S, Najihussien A, et al.

PLoS One, 2014;9(3):e91246.
PMID: 24618844 DOI: 10.1371/journal.pone.0091246

Based on the potential of Schiff base compounds to act as sources for the development of cancer chemotherapeutic agents, this in vivo study was performed to investigate the inhibitory properties of the synthetic Schiff base compound Cu(BrHAP)2 on colonic aberrant crypt foci (ACF).

Matched MeSH terms: Colorectal Neoplasms/metabolism
Analysis of Hereditary Nonpolyposis Colorectal Cancer in Malay Cohorts using Immunohistochemical Screening

Wan Juhari WK, Wan Abdul Rahman WF, Mohd Sidek AS, Abu Hassan MR, Ahmad Amin Noordin KB, Zakaria AD, et al.

Asian Pac J Cancer Prev, 2015;16(9):3767-71.
PMID: 25987035

BACKGROUND: Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) and other cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal or endometrial cancer have the Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1, MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in colorectal cancer in a Malay cohort by immunohistochemistry.
MATERIALS AND METHODS: A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2.
RESULTS: Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively.
CONCLUSIONS: Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.

Matched MeSH terms: Colorectal Neoplasms/metabolism*
Elephantopus scaber induces apoptosis through ROS-dependent mitochondrial signaling pathway in HCT116 human colorectal carcinoma cells

Chan CK, Supriady H, Goh BH, Kadir HA

J Ethnopharmacol, 2015 Jun 20;168:291-304.
PMID: 25861953 DOI: 10.1016/j.jep.2015.03.072

Elephantopus scaber also known as Elephant's foot (Asteraceae family) has a plethora of traditional applications including dysuria, diarrhea, dysentery, leukemia and cancer. This study aimed to investigate the apoptosis inducing effects of E. scaber and the underlying mechanisms in HCT116 colorectal cell line.

Matched MeSH terms: Colorectal Neoplasms/metabolism*
Molecular alterations of Ras-Raf-mitogen-activated protein kinase and phosphatidylinositol 3-kinase-Akt signaling pathways in colorectal cancers from a tertiary hospital at Kuala Lumpur, Malaysia

Yip WK, Choo CW, Leong VC, Leong PP, Jabar MF, Seow HF

APMIS, 2013 Oct;121(10):954-66.
PMID: 23992303 DOI: 10.1111/apm.12152

Molecular alterations in KRAS, BRAF, PIK3CA, and PTEN have been implicated in designing targeted therapy for colorectal cancer (CRC). The present study aimed to determine the status of these molecular alterations in Malaysian CRCs as such data are not available in the literature. We investigated the mutations of KRAS, BRAF, and PTEN, the gene amplification of PIK3CA, and the protein expression of PTEN and phosphatidylinositol 3-kinase (PI3K) catalytic subunit (p110α) by direct DNA sequencing, quantitative real-time PCR, and immunohistochemistry, respectively, in 49 CRC samples. The frequency of KRAS (codons 12, 13, and 61), BRAF (V600E), and PTEN mutations, and PIK3CA amplification was 25.0% (11/44), 2.3% (1/43), 0.0% (0/43), and 76.7% (33/43), respectively. Immunohistochemical staining demonstrated loss of PTEN protein in 54.5% (24/44) of CRCs and no significant difference in PI3K p110α expression between CRCs and the adjacent normal colonic mucosa (p = 0.380). PIK3CA amplification was not associated with PI3K p110α expression level, but associated with male cases (100% of male cases vs 56% of female cases harbored amplified PIK3CA, p = 0.002). PI3K p110α expression was significantly higher (p = 0.041) in poorly/moderately differentiated carcinoma compared with well-differentiated carcinoma. KRAS mutation, PIK3CA amplification, PTEN loss, and PI3K p110α expression did not correlate with Akt phosphorylation or Ki-67 expression. KRAS mutation, PIK3CA amplification, and PTEN loss were not mutually exclusive. This is the first report on CRC in Malaysia showing comparable frequency of KRAS mutation and PTEN loss, lower BRAF mutation rate, higher PIK3CA amplification frequency, and rare PTEN mutation, as compared with published reports.

Matched MeSH terms: Colorectal Neoplasms/metabolism