MyMedR

Fulltext A natural compound from Hydnophytum formicarium induces apoptosis of MCF-7 cells via up-regulation of Bax

Abdullah H, Pihie AHL, Hohmann J, Molnár J

Cancer Cell Int, 2010 May 04;10:14.

PMID: 20441573 DOI: 10.1186/1475-2867-10-14

BACKGROUND: Hydnophytum formicarium Jack is an epyphytic shrub that belongs to the family of Rubiaceae and is native to the tropical rain forests of the Asean region, which includes Malaysia. A flavanoid derivative, 7, 3', 5'-trihydroxyflavanone (3HFD), isolated from H. formicarium has been reported to have cytotoxic effects on the human breast carcinoma cell line MCF-7. The aim of the current study was to investigate the mode of cell death in MCF-7 cells treated with 3HFD. A DNA fragmentation assay was conducted on isolated genomic DNA, a TUNEL assay was used to determine the mode of cell death and Western blotting was used to evaluate the expression levels of Bax and Bcl-2. Immunofluorescence staining of MCF-7 cells was also performed to confirm the up-regulation of the Bax protein.

RESULTS: The ladder pattern resulting from the DNA fragmentation assay was a multimer of 180 kb. The morphological changes of cells undergoing apoptosis were visualised by a TUNEL assay over time. The percentage of apoptotic cells increased as early as 6 hours post treatment compared to untreated cells. Western blotting revealed up-regulation of the pro-apoptotic protein Bax. However, 3HFD did not affect expression of the anti-apoptotic protein Bcl-2.

CONCLUSIONS: Our results provide evidence that plant-derived 3HFD was able to induce the apoptotic cell death of MCF-7 cells by increasing Bax expression level and makes 3HFD a promising agent for chemotherapy, which merits further study.

Fulltext Antiangiogenic properties of Koetjapic acid, a natural triterpene isolated from Sandoricum koetjaoe Merr

Nassar ZD, Aisha AF, Ahamed MB, Ismail Z, Abu-Salah KM, Alrokayan SA, et al.

Cancer Cell Int, 2011;11(1):12.

PMID: 21524294 DOI: 10.1186/1475-2867-11-12

Angiogenesis, the formation of new blood vessels, has become an important target in cancer therapy. Angiogenesis plays an important role in tumor growth and metastasis. Koetjapic acid (KA) is a seco-A-ring oleanene triterpene isolated from S. koetjape. The solvent extract of this plant species was shown previously to have strong antiangiogenic activity; however the active ingredient(s) that conferred the biological activity and the mode of action was not established. Given the high concentration of KA in S. koetjape, an attempt has been made in this study to investigate the antiangiogenic properties of KA.

Fulltext Calreticulin mediates an invasive breast cancer phenotype through the transcriptional dysregulation of p53 and MAPK pathways

Zamanian M, Qader Hamadneh LA, Veerakumarasivam A, Abdul Rahman S, Shohaimi S, Rosli R

Cancer Cell Int, 2016;16:56.

PMID: 27418879 DOI: 10.1186/s12935-016-0329-y

The introduction of effective novel biomarkers of invasion and metastasis is integral for the advancement of breast cancer management. The present study focused on the identification and evaluation of calreticulin (CRT) as a potential biomarker for breast cancer invasion.

Fulltext Combined xanthorrhizol-curcumin exhibits synergistic growth inhibitory activity via apoptosis induction in human breast cancer cells MDA-MB-231

Cheah YH, Nordin FJ, Sarip R, Tee TT, Azimahtol HL, Sirat HM, et al.

Cancer Cell Int, 2009;9:1.

PMID: 19118501 DOI: 10.1186/1475-2867-9-1

It has been suggested that combined effect of natural products may improve the treatment effectiveness in combating proliferation of cancer cells. The present study was undertaken to evaluate the possibility that the combination of xanthorrhizol and curcumin might show synergistic growth inhibitory effect towards MDA-MB-231 human breast cancer cells via apoptosis induction. The effective dose that produced 50% growth inhibition (GI50) was calculated from the log dose-response curve of fixed-combinations of xanthorrhizol and curcumin generated from the sulforhodamine B (SRB) assay. The experimental GI50 value was used to determine the synergistic activity of the combination treatment by isobolographic analysis and combination-index method. Further investigation of mode of cell death induced by the combination treatment was conducted in the present study.

Fulltext Comparative secretomic and N-glycoproteomic profiling in human MCF-7 breast cancer and HMEpC normal epithelial cell lines using a gel-based strategy

Tan AA, Mu AK, Kiew LV, Chen Y

Cancer Cell Int, 2014;14(1):120.

PMID: 25484625 DOI: 10.1186/s12935-014-0120-x

Concurrent study of secretomic and glycoproteomic profiles in cancer cell lines represents an excellent approach for investigating cancer progression and identifying novel biomarker candidates. In this study, we performed a comparative secretomic and N-glycoprotein profiling from the secretions of normal human mammary epithelial cells (HMEpC) and the MCF-7 human breast cancer cell line.

Fulltext Cytotoxicity study of the interleukin-12-expressing recombinant Newcastle disease virus strain, rAF-IL12, towards CT26 colon cancer cells in vitro and in vivo

Najmuddin SUFS, Amin ZM, Tan SW, Yeap SK, Kalyanasundram J, Ani MAC, et al.

Cancer Cell Int, 2020;20:278.

PMID: 32612457 DOI: 10.1186/s12935-020-01372-y

Background: Oncolytic viruses have emerged as an alternative therapeutic modality for cancer as they can replicate specifically in tumour cells and induce toxic effects leading to apoptosis. Despite the great potentials and promising results shown in multiple studies, it appears that their efficacy is still moderate and deemed as not sufficient in clinical studies. In addressing this issue, genetic/molecular engineering approach has paved its way to improve the therapeutic efficacy as observed in the case of herpes simplex virus (HSV) expressing granulocyte-macrophage colony-stimulating factor (GM-CSF). This study aimed to explore the cytotoxicity effects of recombinant NDV strain AF2240-i expressing interleukin-12 (rAF-IL12) against CT26 colon cancer cells.

Methods: The cytotoxicity effect of rAF-IL12 against CT26 colon cancer cell line was determined by MTT assay. Based on the IC50 value from the anti-proliferative assay, further downward assays such as Annexin V FITC and cell cycle progression were carried out and measured by flow cytometry. Then, the in vivo study was conducted where the rAF-IL12 viral injections were given at the intra-tumoral site of the CT26 tumour-burden mice. At the end of the experiment, serum biochemical, T cell immunophenotyping, serum cytokine, histopathology of tumour and organ section, TUNEL assay, and Nanostring gene expression analysis were performed.

Results: The rAF-IL12 induced apoptosis of CT26 colon cancer cells in vitro as revealed in the Annexin V FITC analysis and also arrested the cancer cells progression at G1 phase of the cell cycle analysis. On the other hand, the rAF-IL12 significantly (p

Fulltext Determination of the differentiation capacities of murines' primary mononucleated cells and MC3T3-E1 cells

Yazid MD, Ariffin SH, Senafi S, Razak MA, Wahab RM

Cancer Cell Int, 2010;10:42.

PMID: 20979664 DOI: 10.1186/1475-2867-10-42

The main morphological features of primitive cells, such as stem and progenitor cells, are that these cells consists only one nucleus. The main purpose of this study was to determine the differentiation capacities of stem and progenitor cells. This study was performed using mononucleated cells originated from murine peripheral blood and MC3T3-E1 cells. Three approaches were used to determine their differentiation capacities: 1) Biochemical assays, 2) Gene expression analysis, and 3) Morphological observations.

Fulltext Establishment and characterization of two human breast carcinoma cell lines by spontaneous immortalization: Discordance between Estrogen, Progesterone and HER2/neu receptors of breast carcinoma tissues with derived cell lines

Kamalidehghan B, Houshmand M, Kamalidehghan F, Jafarzadeh N, Azari S, Akmal SN, et al.

Cancer Cell Int, 2012;12(1):43.

PMID: 23106969 DOI: 10.1186/1475-2867-12-43

Fulltext Eurycomanone induce apoptosis in HepG2 cells via up-regulation of p53

Zakaria Y, Rahmat A, Pihie AH, Abdullah NR, Houghton PJ

Cancer Cell Int, 2009;9:16.

PMID: 19508737 DOI: 10.1186/1475-2867-9-16

Eurycomanone is a cytotoxic compound found in Eurycoma longifolia Jack. Previous studies had noted the cytotoxic effect against various cancer cell lines. The aim of this study is to investigate the cytotoxicity against human hepato carcinoma cell in vitro and the mode of action. The cytotoxicity of eurycomanone was evaluated using MTT assay and the mode of cell death was detected by Hoechst 33258 nuclear staining and flow cytometry with Annexin-V/propidium iodide double staining. The protein expression Bax, Bcl-2, p53 and cytochrome C were studied by flow cytometry using a spesific antibody conjugated fluorescent dye to confirm the up-regulation of p53 and Bax in cancer cells.

Fulltext Evaluation of stem-like side population cells in a recurrent nasopharyngeal carcinoma cell line

Hoe SL, Tan LP, Jamal J, Peh SC, Ng CC, Zhang WC, et al.

Cancer Cell Int, 2014;14(1):101.

PMID: 25317078 DOI: 10.1186/s12935-014-0101-0

Side population (SP) assay identifies cells with dye/drug extrusion ability, a characteristic of stem cells. Here, we determined if SP cells exist in a verified cell line originating from recurrent nasopharyngeal carcinoma (NPC) and a xenograft established from recurrent metastatic NPC. These cells were evaluated for stem-like properties via functional assays as well as for tumourigenicity.

Fulltext Inhibitor of caspase-activated DNase expression enhances caspase-activated DNase expression and inhibits oxidative stress-induced chromosome breaks at the mixed lineage leukaemia gene in nasopharyngeal carcinoma cells

Boon SS, Sim SP

Cancer Cell Int, 2015;15:54.

PMID: 26019688 DOI: 10.1186/s12935-015-0205-1

Nasopharyngeal carcinoma (NPC) is commonly found in Asia, especially among the Chinese ethnic group. Chromosome rearrangements are common among NPC patients. Although the mechanism underlying the chromosome rearrangements in NPC is unclear, various mechanisms including activation of caspase-activated DNase (CAD) were proposed to contribute to chromosome rearrangements in leukaemia. Activation of CAD can be initiated by multiple agents, including oxidative stress, which is well implicated in carcinogenesis. CAD is the main enzyme that causes DNA fragmentation during apoptosis, and CAD is also implicated in promoting cell differentiation. In view of the role of oxidative stress in carcinogenesis and CAD activation, and since CAD was suggested to contribute to chromosome rearrangement in leukaemia, we hypothesise that oxidative stress-induced CAD activation could be one of the mechanisms that leads to chromosome rearrangements in NPC.

Fulltext Intrinsic anticarcinogenic effects of Piper sarmentosum ethanolic extract on a human hepatoma cell line

Zainal Ariffin SH, Wan Omar WH, Zainal Ariffin Z, Safian MF, Senafi S, Megat Abdul Wahab R

Cancer Cell Int, 2009;9:6.

PMID: 19257877 DOI: 10.1186/1475-2867-9-6

Piper sarmentosum, locally known as kaduk is belonging to the family of Piperaceae. It is our interest to evaluate their effect on human hepatoma cell line (HepG2) for the potential of anticarcinogenic activity.

Fulltext Knockdown of PLC-gamma-2 and calmodulin 1 genes sensitizes human cervical adenocarcinoma cells to doxorubicin and paclitaxel

Stanislaus A, Bakhtiar A, Salleh D, Tiash S, Fatemian T, Hossain S, et al.

Cancer Cell Int, 2012 Jun 18;12(1):30.

PMID: 22709569 DOI: 10.1186/1475-2867-12-30

BACKGROUND: RNA interference (RNAi) is a powerful approach in functional genomics to selectively silence messenger mRNA (mRNA) expression and can be employed to rapidly develop potential novel drugs against a complex disease like cancer. However, naked siRNA being anionic is unable to cross the anionic cell membrane through passive diffusion and therefore, delivery of siRNA remains a major hurdle to overcome before the potential of siRNA technology can fully be exploited in cancer. pH-sensitive carbonate apatite has recently been developed as an efficient tool to deliver siRNA into the mammalian cells by virtue of its high affinity interaction with the siRNA and the desirable size distribution of the resulting siRNA-apatite complex for effective cellular endocytosis. Moreover, internalized siRNA was found to escape from the endosomes in a time-dependent manner and efficiently silence gene expression.

RESULTS: Here we show that carbonate apatite-mediated delivery of siRNA against PLC-gamma-2 (PLCG2) and calmodulin 1 (CALM1) genes has led to the sensitization of a human cervical cancer cell line to doxorubicin- and paclitaxel depending on the dosage of the individual drug whereas no such enhancement in cell death was observed with cisplatin irrespective of the dosage following intracellular delivery of the siRNAs.

CONCLUSION: Thus, PLCG2 and CALM1 genes are two potential targets for gene knockdown in doxorubicin and paclitaxel-based chemotherapy of cervical cancer.

Luteolin: a flavonoid with a multifaceted anticancer potential

Prasher P, Sharma M, Singh SK, Gulati M, Chellappan DK, Zacconi F, et al.

Cancer Cell Int, 2022 Dec 08;22(1):386.

PMID: 36482329 DOI: 10.1186/s12935-022-02808-3

Therapeutic effect of phytochemicals has been emphasized in the traditional medicine owing to the presence of bioactive molecules, such as polyphenols. Luteolin is a flavone belonging to the flavonoid class of polyphenolic phytochemicals with healing effect on hypertension, inflammatory disorders, and cancer due to its action as pro-oxidants and antioxidants. The anticancer profile of luteolin is of interest due to the toxic effect of contemporary chemotherapy paradigm, leading to the pressing need for the development and identification of physiologically benevolent anticancer agents and molecules. Luteolin exerts anticancer activity by downregulation of key regulatory pathways associated with oncogenesis, in addition to the induction of oxidative stress, cell cycle arrest, upregulation of apoptotic genes, and inhibition of cell proliferation and angiogenesis in cancer cells. In this review, we discuss about the anticancer profile of luteolin.

Fulltext Nuclear localization and intensity of staining of nm23 protein is useful marker for breast cancer progression

Ismail NI, Kaur G, Hashim H, Hassan MS

Cancer Cell Int, 2008;8:6.

PMID: 18454879 DOI: 10.1186/1475-2867-8-6

Breast cancer is the most common cause of cancer death in the western world. The expression differences of many proteins are associated with breast cancer progression or suppression. The purpose of the study was to determine the expression of nm23 protein in the invasion status and metastatic potential of breast cancer by using tissue microarray and to determine its role in breast cancer based on the expression of nm23 gene product.

Fulltext Nucleofection optimization and in vitro anti-tumourigenic effect of TRAIL-expressing human adipose-derived mesenchymal stromal cells

Fakiruddin KS, Baharuddin P, Lim MN, Fakharuzi NA, Yusof NA, Zakaria Z

Cancer Cell Int, 2014;14(1):122.

PMID: 25469108 DOI: 10.1186/s12935-014-0122-8

Tumour homing capacity of engineered human adipose-derived mesenchymal stromal cells (ADMSCs) expressing anti-tumour agents might be the key for a much safer and yet efficient targeted tumour therapy. However, ADMSCs exhibit resistant to most gene transfection techniques and the use of highly efficient viral vectors has several disadvantages primarily concerning safety risk. Here, we optimized the use of highly efficient and safe nucleofection-based transfection using plasmid encoded for TNF-Related Apoptosis Inducing Ligand (TRAIL) into ADMSCs and investigated the potential anti-tumourigenic of TRAIL-expressing ADMSCs (ADMSCs-TRAIL) on selected cancer models in vitro.

Quercetin-induced inhibition and synergistic activity with cisplatin - a chemotherapeutic strategy for nasopharyngeal carcinoma cells

Daker M, Ahmad M, Khoo AS

Cancer Cell Int, 2012;12(1):34.

PMID: 22809533

Nasopharyngeal carcinoma (NPC) is a unique tumour of epithelial origin with a distinct geographical distribution, genetic predisposition and environmental as well as dietary influence as aetiological factors. Standard NPC treatment regimes, such as radiotherapy and concurrent chemotherapy with cytotoxic drugs, can produce undesirable complications often associated with significant toxicity. Here, we report the effects of a widely distributed flavonoid, quercetin, on cell proliferation, apoptosis and cell cycle arrest. The effects of combining quercetin and cisplatin on human NPC cells were explored.

Fulltext Reduced Newcastle disease virus-induced oncolysis in a subpopulation of cisplatin-resistant MCF7 cells is associated with survivin stabilization

Jamal MH, Ch'ng WC, Yusoff K, Shafee N

Cancer Cell Int, 2012 Aug 01;12(1):35.

PMID: 22853623 DOI: 10.1186/1475-2867-12-35

BACKGROUND: Cisplatin resistance is a serious problem in cancer treatment. To overcome it, alternative approaches including virotherapy are being pursued. One of the candidates for anticancer virotherapy is the Newcastle disease virus (NDV). Even though NDV's oncolytic properties in various cancer cells have been widely reported, information regarding its effects on cisplatin resistant cancer cells is still limited. Therefore, we tested the oncolytic efficacy of a strain of NDV, designated as AF2240, in a cisplatin-resistant breast cancer cell line.

METHODS: Cisplatin-resistant cell line (MCF7-CR) was developed from the MCF7 human breast adenocarcinoma cell line by performing a seven-cyclic exposure to cisplatin. Following NDV infection, fluorescence-activated cell sorting (FACS) analysis and immunoblotting were used to measure cell viability and viral protein expression, respectively. Production of virus progeny was then assessed by using the plaque assay technique.

RESULTS: Infection of a mass population of the MCF7-CR with NDV resulted in 50% killing in the first 12 hours post-infection (hpi), comparable to the parental MCF7. From 12 hpi onwards, the remaining MCF7-CR became less susceptible to NDV killing. This reduced susceptibility led to increased viral protein synthesis and virus progeny production. The reduction was also associated with a prolonged cell survival via stabilization of the survivin protein.

CONCLUSIONS: Our findings showed for the first time, the involvement of survivin in the reduction of NDV-induced oncolysis in a subpopulation of cisplatin-resistant cells. This information will be important towards improving the efficacy of NDV as an anticancer agent in drug resistant cancers.

Fulltext S100A4 overexpression proves to be independent marker for breast cancer progression

Ismail NI, Kaur G, Hashim H, Hassan MS

Cancer Cell Int, 2008 Sep 05;8:12.

PMID: 18771601 DOI: 10.1186/1475-2867-8-12

BACKGROUND: Breast cancer is the most common cancer and cause of deaths in women around the world. Oncogene amplification usually occurs late in tumor progression and correlates well with aggressiveness of tumor. In fact the function of the S100A4 protein and its role in metastasis is unclear at present. The purpose of the study was to determine the expression of S100A4 protein in the invasion status and metastatic potential of breast cancer by using tissue microarray and to determine its role in breast cancer based on the expression of S100A4 gene product.

METHODS: S100A4 protein expression was examined by immunohistochemistry (IHC) using commercially available tissue microarray containing malignant and normal breast tissue cores from 216 patients.

RESULTS: S100A4 was absent in normal breast tissues while positive in 45.1% of infiltrating ductal carcinoma (IDC) node negative and 48.8% of infiltrating lobular carcinoma node negative. In paired samples, S100A4 protein was expressed in 13.5% of IDC node positive cases and 35.1% of matched lymph node metastasis.

CONCLUSION: S100A4 protein expression appears widely expressed in early and advanced breast cancer stages compared with normal breast. Our study suggests S100A4 may play a role in breast cancer progression and may prove to be an independent marker of breast cancer which appears to be down regulated in more advanced stages of breast cancer.

Styrylpyrone Derivative (SPD) induces apoptosis in a caspase-7-dependent manner in the human breast cancer cell line MCF-7

Lee AT, Azimahtol HL, Tan AN

Cancer Cell Int, 2003 Oct 4;3(1):16.

PMID: 14580263

BACKGROUND: Styrylpyrone derivative (SPD) is a plant-derived pharmacologically active compound extracted from Goniothalamus sp. Previously, we have reported that SPD inhibited the proliferation of MCF-7 human breast cancer cells by inducing apoptotic cell death, while having minimal effects on non-malignant cells. Here, we attempt to further elucidate the mode of action of SPD. RESULTS: We found that the intrinsic apoptotic pathway was invoked, with the accumulation of cytosolic cytochrome c and processing of the initiator caspase-9. Cleaved products of procaspase-8 were not detected. Next, the executioner caspase-7 was cleaved and activated in response to SPD treatment. To confirm that apoptosis was induced following caspase-7 activation, the caspase inhibitor Ac-DEVD-CHO was used. Pre-incubation of cells with this inhibitor reversed apoptosis levels and caspase-7 activity in SPD-treated cells to untreated levels. CONCLUSIONS: Taken together, these results suggest SPD as a potent antiproliferative agent on MCF-7 cells by inducing apoptosis in a caspase-7-dependent manner.

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