Displaying publications 81 - 95 of 95 in total

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  1. Wong HC, Wong CC, Sagineedu SR, Loke SC, Lajis NH, Stanslas J
    Cell Biol Toxicol, 2014 Oct;30(5):269-88.
    PMID: 25070834 DOI: 10.1007/s10565-014-9282-5
    3,19-(3-Chloro-4-fluorobenzylidene)andrographolide (SRJ23), a new semisynthetic derivative of andrographolide (AGP), exhibited selectivity against prostate cancer cells in the US National Cancer Institute (NCI) in vitro anti-cancer screen. Herein, we report the in vitro growth inhibition and mechanisms of cell cycle arrest and apoptosis induced by SRJ23.
  2. Ramachandran V, Ismail P, Stanslas J, Shamsudin N
    PMID: 19243623 DOI: 10.1186/1475-2840-8-11
    The renin-angiotensin aldosterone system (RAAS) plays an important role in regulating the blood pressure and the genetic polymorphisms of RAAS genes has been extensively studied in relation to the cardiovascular diseases in various populations with conflicting results. The aim of this study was to determine the association of five genetic polymorphisms (A6G and A20C of angiotensinogen (AGT), MboI of renin, Gly460Trp of aldosterone synthase and Lys173Arg of adducin) of RAAS genes in Malaysian essential hypertensive and type 2 diabetic subjects.
  3. Tan SC, Poh WT, Yong ACH, Chua EW, Ooi J, Mahmud R, et al.
    Cancer Manag Res, 2023;15:851-862.
    PMID: 37636030 DOI: 10.2147/CMAR.S420890
    Considerable progress has been made in cancer drug development in recent decades. However, for people in low- and middle-income countries, including Malaysia, many of these drugs are not readily available. During the 2nd Malaysian Association for Cancer Research (MACR) International Scientific Conference, a forum discussion was held to address these challenges and explore strategies to improve access to cancer medicines in the country. This paper presents the results of the said forum discussion. A few challenges to cancer drug access were highlighted, including lengthy approval and regulatory practices, cost of medicines, and manufacturing barriers. Besides, a few strategies for mitigating some of these challenges were proposed, such as mechanisms for cost reduction, uptake of biosimilars and generics, local manufacturing, public-private partnerships, strengthening the role of insurance companies, funding and regulation, and advocacy for fair pricing, by drawing examples from cancer medicines access initiatives in Malaysia and initiatives for different disease groups. Overall, this paper provides a comprehensive overview of the challenges and strategies for improving access to cancer medicines in Malaysia and provides valuable insights for policymakers, healthcare providers, the pharmaceutical industry, cancer patients, cancer support groups, and other stakeholders working on this important issue.
  4. Jada SR, Matthews C, Saad MS, Hamzah AS, Lajis NH, Stevens MF, et al.
    Br J Pharmacol, 2008 Nov;155(5):641-54.
    PMID: 18806812 DOI: 10.1038/bjp.2008.368
    BACKGROUND AND PURPOSE: Andrographolide, the major phytoconstituent of Andrographis paniculata, was previously shown by us to have activity against breast cancer. This led to synthesis of new andrographolide analogues to find compounds with better activity than the parent compound. Selected benzylidene derivatives were investigated for their mechanisms of action by studying their effects on the cell cycle progression and cell death.
    EXPERIMENTAL APPROACH: Microculture tetrazolium, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and sulphorhodamine B (SRB) assays were utilized in assessing the in vitro growth inhibition and cytotoxicity of compounds. Flow cytometry was used to analyse the cell cycle distribution of control and treated cells. CDK1 and CDK4 levels were determined by western blotting. Apoptotic cell death was assessed by fluorescence microscopy and flow cytometry.
    KEY RESULTS: Compounds, in nanomolar to micromolar concentrations, exhibited growth inhibition and cytotoxicity in MCF-7 (breast) and HCT-116 (colon) cancer cells. In the NCI screen, 3,19-(2-bromobenzylidene) andrographolide (SRJ09) and 3,19-(3-chloro-4-fluorobenzylidene) andrographolide (SRJ23) showed greater cytotoxic potency and selectivity than andrographolide. SRJ09 and SRJ23 induced G(1) arrest and apoptosis in MCF-7 and HCT-116 cells, respectively. SRJ09 downregulated CDK4 but not CDK1 level in MCF-7 cells. Apoptosis induced by SRJ09 and SRJ23 in HCT-116 cells was confirmed by annexin V-FITC/PI flow cytometry analysis.
    CONCLUSION AND IMPLICATIONS: The new benzylidene derivatives of andrographolide are potential anticancer agents. SRJ09 emerged as the lead compound in this study, exhibiting anticancer activity by downregulating CDK4 to promote a G(1) phase cell cycle arrest, coupled with induction of apoptosis.
  5. Saik AY, Lim YY, Stanslas J, Choo WS
    Biotechnol Lett, 2017 Feb;39(2):297-304.
    PMID: 27812823 DOI: 10.1007/s10529-016-2246-5
    OBJECTIVES: To investigate the lipase-catalyzed acylation of quercetin with oleic acid using Candida antarctica lipase B.

    RESULTS: Three acylated analogues were produced: quercetin 4'-oleate (C33H42O8), quercetin 3',4'-dioleate (C51H74O9) and quercetin 7,3',4'-trioleate (C69H106O10). Their identities were confirmed with UPLC-ESI-MS and (1)H NMR analyses. The effects of temperature, duration and molar ratio of substrates on the bioconversion yields varied across conditions. The regioselectivity of the acylated quercetin analogues was affected by the molar ratio of substrates. TLC showed the acylated analogues had higher lipophilicity (152% increase) compared to quercetin. Partition coefficient (log P) of quercetin 4'-oleate was higher than those of quercetin and oleic acid. Quercetin 4'-oleate was also stable over 28 days of storage.

    CONCLUSIONS: Quercetin oleate esters with enhanced lipophilicity can be produced via lipase-catalyzed reaction using C. antarctica lipase B to be used in topical applications.

  6. Shaari K, Suppaiah V, Wai LK, Stanslas J, Tejo BA, Israf DA, et al.
    Bioorg Med Chem, 2011 Nov 1;19(21):6340-7.
    PMID: 21958738 DOI: 10.1016/j.bmc.2011.09.001
    A bioassay-guided investigation of Melicope ptelefolia Champ ex Benth (Rutaceae) resulted in the identification of an acyphloroglucinol, 2,4,6-trihydroxy-3-geranylacetophenone or tHGA, as the active principle inhibiting soybean 15-LOX. The anti-inflammatory action was also demonstrated on human leukocytes, where the compound showed prominent inhibitory activity against human PBML 5-LOX, with an IC(50) value of 0.42 μM, very close to the effect produced by the commonly used standard, NDGA. The compound concentration-dependently inhibited 5-LOX product synthesis, specifically inhibiting cysteinyl leukotriene LTC(4) with an IC(50) value of 1.80 μM, and showed no cell toxicity effects. The anti-inflammatory action does not seem to proceed via redox or metal chelating mechanism since the compound tested negative for these bioactivities. Further tests on cyclooxygenases indicated that the compound acts via a dual LOX/COX inhibitory mechanism, with greater selectivity for 5-LOX and COX-2 (IC(50) value of 0.40 μM). The molecular features that govern the 5-LOX inhibitory activity was thus explored using in silico docking experiments. The residues Ile 553 and Hie 252 were the most important residues in the interaction, each contributing significant energy values of -13.45 (electrostatic) and -5.40 kcal/mol (electrostatic and Van der Waals), respectively. The hydroxyl group of the phloroglucinol core of the compound forms a 2.56Å hydrogen bond with the side chain of the carboxylate group of Ile 553. Both Ile 553 and Hie 252 are crucial amino acid residues which chelate with the metal ion in the active site. Distorting the geometry of these ligands could be the reason for the inhibition activity shown by tHGA. The molecular simulation studies supported the bioassay results and served as a good model for understanding the way tHGA binds in the active site of human 5-LOX enzyme.
  7. Poh Yen K, Stanslas J, Zhang T, Li H, Wang X, Kok Meng C, et al.
    Bioorg Med Chem, 2021 11 01;49:116442.
    PMID: 34600241 DOI: 10.1016/j.bmc.2021.116442
    Acquired paclitaxel (PTX) chemoresistance in triple-negative breast cancer (TNBC) can be inferred from the overexpression of toll-like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) proteins and the activation of the TLR4/MyD88 cascading signalling pathway. Finding a new inhibitor that can attenuate the activation of this pathway is a novel strategy for reducing PTX chemoresistance. In this study, a series of small molecule compounds were synthesised and tested in combination with PTX against TNBC cells. The trimethoxy-substituted compound significantly decreased MyD88 overexpression and improved PTX activity in MDA-MB-231TLR4+ cells but not in HCCTLR4- cells. On the contrary, the trifluoromethyl-substituted compound with PTX synergistically improved the growth inhibition in both TNBC subtypes. The fluorescence titrations indicated that both compounds could bind with MD2 with good and comparable binding affinities. This was further supported by docking analysis, in which both compounds fit perfectly well and form some critical binding interactions with MD2, an essential lipid-binding accessory to TLR4 involved in activating the TLR-4/MyD88-dependent pathway.
  8. Jabir RS, Ho GF, Annuar MABA, Stanslas J
    Biomarkers, 2018 Mar;23(2):142-146.
    PMID: 28554261 DOI: 10.1080/1354750X.2017.1334152
    CONTEXT: Rash and oral mucositis are major non-haematological adverse events (AEs) of docetaxel, in addition to fatigue, nausea, vomiting and diarrhoea, which restrict the use of the drug in cancer therapy. Alpha-1-acid glycoprotein (AAG) is an acute phase reactant glycoprotein and is a primary carrier of docetaxel in the blood. Docetaxel has extensive binding (>98%) to plasma proteins such as AAG, lipoproteins and albumin.

    OBJECTIVE: To study the association between plasma AAG level and non-haematological AEs of docetaxel in Malaysian breast cancer patients of three major ethnic groups (Malays, Chinese and Indians).

    MATERIALS AND METHODS: One hundred and twenty Malaysian breast cancer patients receiving docetaxel as single agent chemotherapy were investigated for AAG plasma level using enzyme-linked immunosorbent assay technique. Toxicity assessment was determined using Common Terminology Criteria of Adverse Events v4.0. The association between AAG and toxicity were then established.

    RESULTS: There was interethnic variation of plasma AAG level; it was 182 ± 85 mg/dl in Chinese, 237 ± 94 mg/dl in Malays and 240 ± 83 mg/dl in Indians. It was found that low plasma levels of AAG were significantly associated with oral mucositis and rash.

    CONCLUSIONS: This study proposes plasma AAG as a potential predictive biomarker of docetaxel non-haematological AEs namely oral mucositis and rash.

  9. C Thambiah S, Meor Anuar Shuhaili MFR, Chew BH, Samsudin IN, Abdul Rahman H, Stanslas J, et al.
    Biomarkers, 2019 Nov;24(7):659-665.
    PMID: 31342800 DOI: 10.1080/1354750X.2019.1648554
    Introduction: Statin, the first-line treatment for dyslipidaemia, may have suboptimal adherence due to its associated muscle adverse events. These data, however, remain limited. Aim: To determine the association of serum creatine kinase (CK) and SLCO1B1 rs4363657 polymorphism with statin-associated muscle adverse events (SAMAE) among dyslipidaemia participants.
    Methods: This was a prospective cohort study at government health clinics involving newly diagnosed adults with dyslipidaemia. SAMAE were recorded based on the patient's complaint after a month on statin. CK was taken at baseline and follow-up. Genetic profiling was performed for SLCO1B1 rs4363657 polymorphism.
    Results: Among 118 participants, majority were Malay (72%) males (61%) with a mean age of 49 ± 12.2 years old and prescribed lovastatin (61.9). There was a significant association between statin types (lovastatin and simvastatin) and SAMAE (p = 0.0327); no significant association noted between CK and SAMAE (p = 0.5637). The SLCO1B1 rs4363657 polymorphism was significantly associated SAMAE (p 
  10. Sulaiman MR, Zakaria ZA, Abdul Rahman A, Mohamad AS, Desa MN, Stanslas J, et al.
    Biol Res Nurs, 2010 Jan;11(3):293-301.
    PMID: 19689990 DOI: 10.1177/1099800409343311
    The current study was performed to evaluate the antinociceptive and antiedematogenic properties of andrographolide isolated from the leaves of Andrographis paniculata using two animal models. Antinociceptive activity was evaluated using the acetic acid- induced writhing and the hot-plate tests, while antiedematogenic activity was measured using the carrageenan-induced paw edema test. Subcutaneous (s.c.) administration of andrographolide (10, 25, and 50 mg/kg) did not affect the motor coordination of the experimental animals but produced significant (p < .05) antinociceptive activity when assessed using both tests. However, 2 mg/kg naloxone failed to affect the 25 mg/kg andrographolide activity in both tests, indicating that the activity was modulated via nonopioid mechanisms. Furthermore, andrographolide showed significant (p < .05) antiedematogenic activity. In conclusion, the results obtained suggest that andrographolide has antinociceptive and antiedematogenic activities; it may be useful for treating pain and inflammation once human studies are conducted.
  11. Chew YL, Chan EW, Tan PL, Lim YY, Stanslas J, Goh JK
    PMID: 21306653 DOI: 10.1186/1472-6882-11-12
    Many medicinal plants from Leguminosae family can be found easily in Malaysia. These plants have been used as traditional medicines by local ethnic groups, where they are prepared as decoction, pastes for wound infections, and some have been eaten as salad. This paper focused on the assessment of antioxidant potential, antibacterial activity and classes of phytochemicals of nine plants from the Leguminosae family.
  12. Yahaya MAF, Bakar ARA, Stanslas J, Nordin N, Zainol M, Mehat MZ
    BMC Biotechnol, 2021 06 05;21(1):38.
    PMID: 34090414 DOI: 10.1186/s12896-021-00697-4
    BACKGROUND: Neuroinflammation has been identified to be the key player in most neurodegenerative diseases. If neuroinflammation is left to be unresolved, chronic neuroinflammation will be establish. Such situation is due to the overly-activated microglia which have the tendency to secrete an abundance amount of pro-inflammatory cytokines into the neuron microenvironment. The abundance of pro-inflammatory cytokines will later cause toxic and death to neurons. Toll-like receptor 4 (TLR4)/MD-2 complex found on the cell surface of microglia is responsible for the attachment of LPS and activation of nuclear factor-κB (NF-κB) downstream signalling pathway. Albeit vitexin has been shown to possess anti-inflammatory property, however, little is known on its ability to bind at the binding site of TLR4/MD-2 complex of microglia as well as to be an antagonist for LPS.

    RESULTS: The present study reveals that both vitexin and donepezil are able to bind at the close proximity of LPS binding site located at the TLR4/MD-2 complex with the binding energy of - 4.35 and - 9.14 kcal/mol, respectively. During molecular dynamic simulations, both vitexin and donepezil formed stable complex with TLR4/MD-2 throughout the 100 ns time length with the root mean square deviation (RMSD) values of 2.5 Å and 4.0 Å, respectively. The root mean square fluctuation (RMSF) reveals that both compounds are stable. Interestingly, the radius of gyration (rGyr) for donepezil shows notable fluctuations when compare with vitexin. The MM-GBSA results showed that vitexin has higher binding energy in comparison with donepezil.

    CONCLUSIONS: Taken together, the findings suggest that vitexin is able to bind at the binding site of TLR4/MD-2 complex with more stability than donepezil throughout the course of 100 ns simulation. Hence, vitexin has the potential to be an antagonist candidate for LPS.

  13. Hawariah A, Stanslas J
    Anticancer Res, 1998 Nov-Dec;18(6A):4383-6.
    PMID: 9891496
    Previous studies have shown that a styrylpyrone derivative (SPD) from a local tropical plant had antiprogestin and antiestrogenic effects in early pregnant mice models (Azimahtol et al. 1991). Antiprogestins and antiestrogens can be exploited as a therapeutic approach to breast cancer treatment and thus the antitumor activity of SPD was tested in three different human breast cancer cell lines that is: MCF- 7, T47D and MDA-MB-231, employing, the antiproliferative assay of Lin and Hwang (1991) slightly modified. SPD (10(-10) - 10(-6) M) exhibited strong antiproliferative activity in estrogen and progestin-dependent MCF-7 cells (EC50 = 2.24 x 10(-7) M) and in hormone insensitive MDA-MB-231 (EC50 = 5.62 x 10(-7) M), but caused only partial inhibition of the estrogen- insensitive T47D cells (EC50 = 1.58 x 10(-6) M). However, tamoxifen showed strong inhibition of MCF-7 cells (EC50 = 1.41 x 10(-6) M) and to a lesser extent the T47D cells (EC50 = 2.5 x 10(-6) M) but did not affect the MDA-MB-231 cells. SPD at 1 microM exerted a beffer antiestrogenic activity than 1 microM tamoxifen in suppressing the growth of MCF-7 cells stimulated by 1 nM estradiol. Combined treatment of both SPD and tamoxifen at 1 microM showed additional inhibition on the growth of MCF-7 cells in culture. The antiproliferative properties of SPD are effective on both receptor positive and receptor negative mammary cancer cells, and thus appear to be neither dependent on cellular receptor status nor cellular hormone responses. This enhances in vivo approaches as tumors are heterogenous masses with varying receptor status.
  14. Pihie AH, Stanslas J, Din LB
    Anticancer Res, 1998 May-Jun;18(3A):1739-43.
    PMID: 9673398
    The antiproliferative activity of a styrylpyrone derivative (SPD) plant extract, was studied in three different human breast cancer cell lines in culture, and was compared with tamoxifen. The number of living cells was evaluated by Methylene Blue staining technique. SPD showed strong antiproliferative activity in estrogen receptor (ER) and progestin receptor (PgR) positive MCF-7 cells (EC50 = 6.30 x 10(-7) M) and receptor-negative MDA-MB-231 (EC50 = 5.62 x 10(-7) M), but it partially inhibited the high progestin receptor positive T47D cells (EC50 = 1.58 x 10(-6) M). Whereas tamoxifen, a nonsteroidal antiestrogen exhibited strong inhibition on MCF-7 cells (EC50 = 1.41 x 10(-6) M) and partial inhibition on T47D cells (EC50 = 2.5 x 10(-6) M), but did not affect the MDA-MB-231 cells in the concentration range 0.1 nM-1 microM (EC50 = 5.01 microM). At the same concentration range SPD and tamoxifen did not inhibit the proliferation of normal human liver cell line CCL 13 and normal bovine kidney MDBK; whereas adriamycin, a common chemotherapy drug for the treatment of advance cancer, caused 95% inhibition at 10(-6) M. Competitive binding studies showed SPD had no ability to inhibit the binding of [3H]estradiol and [3H]progesterone to ER and PgR, respectively but, tamoxifen exhibited affinity for ER. Therefore, it can be concluded that the antiproliferative activity of SPD was selective towards breast cancer cell lines and not mediated by ER or PgR.
  15. Chew YL, Lim YY, Stanslas J, Ee GC, Goh JK
    PMID: 25371595
    BACKGROUND: Flowers of Bauhinia kockiana were investigated for their anticancer properties.

    METHODS: Gallic acid (1), and methyl gallate (2), were isolated via bioassay-directed isolation, and they exhibited anticancer properties towards several cancer cell lines, examined using MTT cell viability assay. Pyrogallol (3) was examined against the same cancer cell lines to deduce the bioactive functional group of the phenolic compounds.

    RESULTS: The results showed that the phenolic compounds could exhibit moderate to weak cytotoxicity towards certain cell lines (GI50 30 - 86 µM), but were inactive towards DU145 prostate cancer cell (GI50 > 100 µM).

    CONCLUSION: It was observed that pyrogallol moiety was one of the essential functional structures of the phenolic compounds in exhibiting anticancer activity. Also, the carboxyl group of compound 1 was also important in anticancer activity. Examination of the PC-3 cells treated with compound 1 using fluorescence microscopy showed that PC-3 cells were killed by apoptosis.

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