• Archives of Pharmacal Research
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• v.26 no.10
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• pp.832-839
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• 2003

Activated macrophages express inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), and produce excessive amounts of nitric oxide (NO) and prostaglandin E$_2$ (PGE$_2$), which play key roles in the processes of inflammation and carcinogenesis. The root of Paeonia lactiflora Pall., and the root cortex of Paeonia suffruticosa Andr., are important Chinese crude drugs used in many traditional prescriptions. 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (PGG) is a major bioactive constituent of both crude drugs. PGG has been shown to possess potent anti-oxidant, anti-mutagenic, anti-proliferative and anti-invasive effects. In this study, we examined the inhibitory effects of 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (PGG) isolated from the root of Paeonia lactiflora Pall. on the COX-2 and iNOS activity in LPS-activated Raw 264.7 cells, COX-1 in HEL cells. To investigate the structure-activity relationships of gallate and gallic acid for the inhibition of iNOS and COX-2 activity, we also examined (-)-epigallocatechin gallate (EGCG), gallic acid, and gallacetophenone. The results of the present study indicated that PGG, EGCG, and gallacetophenone treatment except gallic acid significantly inhibited LPS-induced NO production in LPS-activated macrophages. All of the four compounds significantly inhibited COX-2 activity in LPS-activated macrophages. Among the four compounds examined, PGG revealed the most potent in both iNOS ($IC_{50}$ = 18 $\mu\textrm{g}/mL$) and COX-2 inhibitory activity (PGE$_2$: $IC_{50}$ = 8 $\mu\textrm{g}/mL$ and PGD$_2$: $IC_{50}$ = 12 $\mu\textrm{g}/mL$), respectively. Although further studies are needed to elucidate the molecular mechanisms and structure-activity relationship by which PGG exerts its inhibitory actions, our results suggest that PGG might be a candidate for developing anti-inflammatory and cancer chemopreventive agents.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3675-3686
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• 2016

Moringa oleifera Lam, family Moringaceae, is a perennial plant which is called various names, but is locally known in Malaysia as ''murungai'' or ''kelor''. Glucomoringin, a glucosinolate with from M. oleifera is a major secondary metabolite compound. The seeds and leaves of the plant are reported to have the highest amount of glucosinolates. M. oleifera is well known for its many uses health and benefits. It is claimed to have nutritional, medicinal and chemopreventive potentials. Chemopreventive effects of M. oleifera are expected due to the existence of glucosinolate which it is reported to have the ability to induce apoptosis in anticancer studies. Furthermore, chemopreventive value of M. oleifera has been demonstrated in studies utilizing its leaf extract to inhibit the growth of human cancer cell lines. This review highlights the advantages of M. oleifera targeting chemoprevention where glucosinolates could help to slow the process of carcinogenesis through several molecular targets. It is also includes inhibition of carcinogen activation and induction of carcinogen detoxification, anti-inflammatory, anti-tumor cell proliferation, induction of apoptosis and inhibition of tumor angiogenesis. Finally, for synergistic effects of M. oleifera with other drugs and safety, essential for chemoprevention, it is important that it safe to be consumed by human body and works well. Although there is promising evidence about M. oleifera in chemoprevention, extensive research need to be done due to the expected rise of cancer in coming years and to gain more information about the mechanisms involved in M. oleifera influence, which could be a good source to inhibit several major mechanisms involved in cancer development.

• BMB Reports
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• v.38 no.6
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• pp.633-638
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• 2005

Biosynthesis of prostanoids is regulated by three sequential enzymatic steps, namely phospholipase $A_2$ enzymes, cyclooxygenase (COX) enzymes, and various lineage-specific terminal prostanoid synthases. Prostaglandin E synthase (PGES), which isomerizes COX-derived $PGH_2$ specifically to $PGE_2$, occurs in multiple forms with distinct enzymatic properties, expressions, localizations and functions. Two of them are membrane-bound enzymes and have been designated as mPGES-1 and mPGES-2. mPGES-1 is a perinuclear protein that is markedly induced by proinflammatory stimuli, is down-regulated by anti inflammatory glucocorticoids, and is functionally coupled with COX-2 in marked preference to COX-1. Recent gene targeting studies of mPGES-1 have revealed that this enzyme represents a novel target for anti-inflammatory and anti-cancer drugs. mPGES-2 is synthesized as a Golgi membrane-associated protein, and the proteolytic removal of the N-terminal hydrophobic domain leads to the formation of a mature cytosolic enzyme. This enzyme is rather constitutively expressed in various cells and tissues and is functionally coupled with both COX-1 and COX-2. Cytosolic PGES (cPGES) is constitutively expressed in a wide variety of cells and is functionally linked to COX-1 to promote immediate $PGE_2$ production. This review highlights the latest understanding of the expression, regulation and functions of these three PGES enzymes.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3619-3622
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• 2016

Background: Triple negative breast cancers (TNBCs) are high grade aggressive tumors generally with a poor prognosis, not responding to hormonal and anti Her2 Neu therapy. Expression of the antiapoptotic B cell lymphoma 2 gene (Bcl-2) is associated with low grade, slowly proliferating hormone receptor positive tumors with improved survival. Anti Bcl2 agents can be used as alternative targeted therapy in triple negative cancers. Materials and Methods: The objective of this study was to determine the immunohistochemical expression of Bcl2 in triple negative breast cancers and any correlation with clinicopathological variables in Northern Pakistan. Results: All 52 patients were females, aged between 28 and 80 years(average $48.0{\pm}12.1$). 28 cases (53.8%) were positive for Bcl2, this being associated with low grade invasive ductal carcinomas, lymph node metastasis and lymphovascular invasion. Conclusions: Bcl-2 may be an important prognostic factor and its expression might be used for targeted therapy using Anti Bcl2 drugs.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2883-2888
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• 2016

Background: Breast cancer (BC) is a serious lifestyle disease. There are several prognostic biomarkers like nuclear receptors whose over-expression is associated with BC characteristics. These biomarkers can be blocked by compounds with anti-cancer potential but selection must be made on the basis of no adverse side effects. This study is focused on finding of compounds from a plant source garlic. Materials and Methods: Twenty compounds from garlic and five targets considered involved in BC were retrieved from Pubchem database and Protein Data Bank respectively. They were docked using Accelrys Discovery Studio (DS) 4.0. The compounds which showed interaction were checked for drug likeliness. Results: Docking studies and ADMET evaluation revealed twelve compounds to be active against the targets. All the compounds displayed highly negative dock scores which indicated good interactions. Conclusions: The results of this study should help researchers and scientists in the pharmaceutical field to identify drugs based on garlic.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2939-2946
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• 2015

Many of the anti-cancer agents currently used have an origin in natural sources including plants. Aloe vera is one such plant being studied extensively for its diverse health benefits, including cancer prevention. In this study, the cytotoxic potential of Aloe vera crude extract (ACE) alone or in combination with cisplatin in human breast (MCF-7) and cervical (HeLa) cancer cells was studied by cell viability assay, nuclear morphological examination and cell cycle analysis. Effects were correlated with modulation of expression of genes involved in cell cycle regulation, apoptosis and drug metabolism by RT-PCR. Exposure of cells to ACE resulted in considerable loss of cell viability in a dose- and time-dependent fashion, which was found to be mediated by through the apoptotic pathway as evidenced by changes in the nuclear morphology and the distribution of cells in the different phases of the cell cycle. Interestingly, ACE did not have any significant cytotoxicity towards normal cells, thus placing it in the category of safe chemopreventive agent. Further, the effects were correlated with the downregulation of cyclin D1, CYP 1A1, CYP 1A2 and increased expression of bax and p21 in MCF-7 and HeLa cells. In addition, low dose combination of ACE and cisplatin showed a combination index less than 1, indicating synergistic growth inhibition compared to the agents applied individually. In conclusion, these results signify that Aloe vera may be an effective anti-neoplastic agent to inhibit cancer cell growth and increase the therapeutic efficacy of conventional drugs like cispolatin. Thus promoting the development of plant-derived therapeutic agents appears warranted for novel cancer treatment strategies.

• Journal of Chest Surgery
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• v.22 no.6
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• pp.914-920
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• 1989

Bleomycin and cyclophosphamide are widely used and effective anti-cancer agents for treatment of various forms of cancer. Bleomycin has no myelotoxicity, but because of potential risk of pulmonary complications including interstitial pneumonitis and idiopathic interstitial pulmonary fibrosis, it has been limited in use. Some investigator has also suggested that cyclophosphamide can induce pulmonary toxicity like bleomycin. Recently, The combination chemotherapy including bleomycin and cyclophosphamide has been adopted effectively in some types of cancer. But there are no available literatures for synergistic effect of pulmonary toxicity in combination chemotherapy including these two drugs. We tried this study to observe synergism of pulmonary toxicity using these two drugs in rats. The animals were divided into five groups: group 1 received intra-peritoneal injection of saline, group 2-a received only bleomycin 0.1 mg [0.4 mg/kg] by intra-peritoneal injection twice a week, group 2-b received only bleomycin 0.5 mg [2 mg/kg] by intra-peritoneal injection twice a week, group 3-a received bleomycin 0.1 mg [0.4 mg/kg] twice a week +cyclophosphamide 5 mg [20 mg/kg] two weeks interval by intra-peritoneal injection, group 3-b received bleomycin 0.5 mg [2 mg/kg] twice a week + cyclophosphamide 5 mg[20 mg/kg] two weeks interval by intra-peritoneal injection. The animals were sacrificed at 2 and 4 weeks later. Lung tissues were obtained and observed by light microscope. The results are as follows: 1. The pathologic findings of group 1 were normal without change. 2. There was no difference between group 2-a and group 3-a at 2 weeks later, group 3-a, however, revealed more severe change in lung tissue at 4 weeks later compared with group 2-a. 3. In group 3-b there was more severe pulmonary injury compared with group 2-b at 2 and 4 weeks later. We conclude that the combined administration of bleomycin and cyclophosphamide induce more severe pulmonary toxic effect than bleomycin administration alone and the combination chemotherapy including these two drugs will be require special attention to selection of the dose of each drug.

• Genomics & Informatics
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• v.19 no.1
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• pp.10.1-10.7
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• 2021

Although many models have been proposed to accurately predict the response of drugs in cell lines recent years, understanding the genome related to drug response is also the key for completing oncology precision medicine. In this paper, based on the cancer cell line gene expression and the drug response data, we established a reliable and accurate drug response prediction model and found predictor genes for some drugs of interest. To this end, we first performed pre-selection of genes based on the Pearson correlation coefficient and then used ElasticNet regression model for drug response prediction and fine gene selection. To find more reliable set of predictor genes, we performed regression twice for each drug, one with IC₅₀ and the other with area under the curve (AUC) (or activity area). For the 12 drugs we tested, the predictive performance in terms of Pearson correlation coefficient exceeded 0.6 and the highest one was 17-AAG for which Pearson correlation coefficient was 0.811 for IC₅₀ and 0.81 for AUC. We identify common predictor genes for IC₅₀ and AUC, with which the performance was similar to those with genes separately found for IC₅₀ and AUC, but with much smaller number of predictor genes. By using only common predictor genes, the highest performance was AZD6244 (0.8016 for IC₅₀, 0.7945 for AUC) with 321 predictor genes.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.324.2-325
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• 2002

Recent studies suggest that inflammatory events are implicated in a variety of human diseases including cancer and neurodegenerative diseases. and non-steroidal anti-inflammatory drugs have beneficial effects in treatment or prevention of these disorders. It has been reported that expression of cyclooxygenase (COX)-2 and nitric oxide synthase and subsequent production of prostaglandin (PG) and nitric oxide (NO). respectively are elevated in many inflammatory disorders. (omitted)

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.187-187
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• 2002

Recent studies suggest that inflammatory events are implicated in a variety of human diseases including cancer and neurodegenerative diseases, and non-steroidal anti-inflammatory drugs have beneficial effects in treatment or prevention of these disorders.(omitted)