Somchaiya Surichan - Academia.edu (original) (raw)

Papers by Somchaiya Surichan

Journal of Virological Methods, Nov 1, 2016

Formulation and quality control of trivalent live-attenuated influenza vaccine requires titration... more Formulation and quality control of trivalent live-attenuated influenza vaccine requires titration of infectivity of individual strains in the trivalent mix. This is usually performed by selective neutralization of two of the three strains and titration of the un-neutralized strain in cell culture or embryonated eggs. This procedure requires standard sera with high neutralizing titer against each of the three strains. Obtaining standard sera, which can specifically neutralize only the corresponding strain of influenza viruses and is able to completely neutralize high concentration of virus in the vaccine samples, can be a problem for many vaccine manufacturers as vaccine stocks usually have very high viral titers and complete neutralization may not be obtained. Here an alternative approach for titration of individual strain in trivalent vaccine without the selective neutralization is presented. This was done by detecting individual strains with specific antibodies in an end-point titration of a trivalent vaccine in cell culture. Similar titers were observed in monovalent and trivalent vaccines for influenza A H3N2 and influenza B strains, whereas the influenza A H1N1 strain did not grow well in cell culture. Viral interference among the vaccine strains was not observed. Therefore, providing that vaccine strains grow well in cell culture, this assay can reliably determine the potency of individual strains in trivalent live-attenuated influenza vaccines.

Vaccine, Jul 1, 2011

In 2005, a year after highly pathogenic avian influenza outbreaks in Thailand, the Thai Governmen... more In 2005, a year after highly pathogenic avian influenza outbreaks in Thailand, the Thai Government issued a National Strategy Plan for Pandemic Influenza Preparedness, a major objective of which was the domestic production of seasonal influenza vaccine. It was considered that sustained influenza vaccine production was the best guarantee of a pandemic vaccine in the event of a future pandemic. The Government decided to provide funds to establish an industrial-scale influenza vaccine production plant, and gave responsibility for this challenging project to the Government Pharmaceutical Organization (GPO). In 2007, with support from the World Health Organization (WHO), the GPO started to develop egg-based, trivalent inactivated influenza vaccine (IIV) in a renovated pilot plant. In early 2009, during the second year of the project, the GPO turned its attention to develop a pandemic live attenuated influenza vaccine (PLAIV) against the influenza A (H1N1) virus. By December 2010, the H1N1 PLAIV had successfully completed Phase II clinical trials and was awaiting registration approval from the Thai Food and Drug Administration (TFDA). The GPO has also started to develop an H5N2 PLAIV, which is expected to enter clinical trials in January 2011. The next step in 2011 will be the development and clinical evaluation of seasonal LAIV. To meet the needs of the national seasonal influenza vaccination programme, the GPO aims to produce 2 million doses of trivalent IIV in 2012 and progressively increase production to the maximum annual capacity of 10 million doses. This article relates how influenza vaccine production capacity was developed and how major challenges are being met in an expeditious manner, with strong local and global commitment.

Breast Cancer Research, May 2, 2008

Introduction The natural product eupatorin has been reported to have antiproliferative activity i... more Introduction The natural product eupatorin has been reported to have antiproliferative activity in tumour cell lines, but the exact mechanism is unclear. The cytochromes P450 CYP1B1, CYP1A1, and CYP1A2 have been shown to participate in the activation of various xenobiotics, compounds derived from the diet as well as chemotherapeutic drugs. CYP1B1 and CYP1A1 have also been proposed as targets for cancer chemotherapy for their differential and selective overexpression in tumour cells. In this study, we aimed to identify a possible mechanism of action for the antiproliferative effect of eupatorin, which can be attributed to CYP1 family-mediated metabolism. Methods The study focuses on the antiproliferative action of eupatorin on the human breast carcinoma cell line MDA-MB-468 and on a cell line derived from normal mammary tissue, MCF-10A. The cytotoxicity of the flavone, its effect on the cell cycle of the abovementioned cell lines, and its metabolism by CYP1 family enzymes were examined. Results Eupatorin showed a dose-dependent inhibitory effect of cell growth on MDA-MB-468 cells with a submicromolar median inhibition concentration (IC 50) whereas the IC 50 of this compound in MCF-10A cells was considerably higher. The antiproliferative effect, as measured by EROD (ethoxyresorufin-O-deethylase) assay and Western immunoblotting, was attributed mainly to CYP1A1 expression in MDA-MB-468 cells but not in MCF-10A cells. Moreover, CYP1 family enzymes were shown to metabolise eupatorin in vitro to the flavone cirsiliol and two other unidentified metabolites. Metabolism of eupatorin was also detected in MDA-MB-468 cell cultures, whereas metabolism by MCF-10A cells was negligible. Eupatorin was further shown to arrest the cell cycle of the CYP1-expressing cell line MDA-MB-468 in G 2 /M phase, whereas no effect was observed in MCF-10A cells, which do not express CYP1 enzymes. The effect of eupatorin on the MDA-MB-468 cell cycle could be reversed by co-application of the CYP1 inhibitor acacetin. Conclusion The flavone eupatorin is selectively activated in breast cancer cells, but not in normal breast cells, due to CYP1 family metabolism. This provides a basis for selectivity which is desired against breast tumour cells. In this sense, eupatorin is shown by this study to be a very promising chemopreventative candidate that should be examined further in an in vivo study.

Phytochemistry Reviews, Apr 9, 2009

It has been generally accepted that regular consumption of fresh fruits and vegetables is linked ... more It has been generally accepted that regular consumption of fresh fruits and vegetables is linked with a relatively low incidence of cancers (e.g. breast, cervix, and colon). A number of plant-derived compounds have been identified that are considered to play a role in cancer prevention. However, at present there is no satisfactory explanation for the cancer preventative properties of the above-mentioned compound groups. The current review is an effort to develop a consistent and unambiguous model that explains how some plant-derived compounds can prevent tumour development. The model is based on recent discoveries in the fields of genomics and drugmetabolism; notably, the discovery that CYP1 genes are highly expressed in developing tumour cells but not in the surrounding tissue, and that a variety of plantderived compounds are substrates for the CYP1 enzymes. Our hypothesis is that some dietary compounds act as prodrugs, i.e. compounds with little or no biological effect as such, but become pharmaceutically effective when activated. More specifically, we state that the abovementioned prodrugs are only activated in CYP1-expressing cells-i.e. cells in the early stages of tumour development-to be converted into compounds which inhibit cell growth. Thus, the prodrugs selectively kill precancerous cells early in tumour development. The review focuses on the identification of naturally-occurring prodrugs that are activated by the tumour-specific CYP1 enzymes and aims to assess their role in cancer prevention.

Vaccine, 2020

Background: The emergence and spread of highly pathogenic avian influenza (H5N1) viruses have rai... more Background: The emergence and spread of highly pathogenic avian influenza (H5N1) viruses have raised global concerns of a possible human pandemic, spurring efforts towards H5N1 influenza vaccine development and improvements in vaccine administration methods. We previously showed that a primeboost vaccination strategy induces robust and broadly cross-reactive antibody responses against the hemagglutinin globular head domain. Here, we specifically measure antibodies against the conserved hemagglutinin stem region in serum samples obtained from the prior study to determine whether stalk-reactive antibodies can also be induced by the prime-boost regimen. Method: Serum samples collected from 60 participants before vaccination and on days 7, 28 and 90 following boosting vaccination were used in this study. 40 participants received two doses of live attenuated H5N2 vaccine (LAIV H5N2) followed by one dose of inactivated H5N1 vaccine a year later, while 20 participants received only the inactivated H5N1 vaccine. We tested these serum samples for stalkreactive antibodies via enzyme-linked immunosorbent (ELISA) and microneutralization assays. Results: Stalk-specific antibody levels measured by both assays were found to be significantly higher in primed individuals than the unprimed group. ELISA results showed that 22.5, 70.5 and 57.5% of primed participants had a four-fold or more increase in stalk antibody titers on days 7, 28 and 90 following boosting vaccination, respectively; whereas the unprimed group had no increase. Peak geometric mean titers (GMT) for stalk antibodies in the LAIV H5N2 experienced group (24,675 [95% CI; 19,531-31,174]) were significantly higher than those who received only the inactivated H5N1 vaccine (8877 [7140-11,035]; p < 0Á0001). Moreover, stalk antibodies displaying neutralizing activity also increased in primed participants, but not in the unprimed group. Conclusion: Our finding emphasizes the importance of prime-boost vaccination for effectively inducing stalk antibodies, which is an attractive target for developing vaccines that induce stalk reactive antibodies.

Phytochemistry Reviews, Jun 14, 2014

It has been widely acknowledged that regular consumption of fresh fruits and vegetables is linked... more It has been widely acknowledged that regular consumption of fresh fruits and vegetables is linked with a relatively low incidence of cancers (e.g. breast, cervix, and colon). Notably, dietary polyphenolic compounds that show some structural similarity to human estrogen, e.g. isoflavones, coumestans, lignans, flavones, have been proposed to play a role in cancer prevention. However, at present there is no satisfactory explanation for the cancer preventative properties of this group of compounds. Whereas polyphenolic compounds have been shown to inhibit proliferation of tumour cells in vitro, the results of in vivo tests have mostly been disappointing in this respect. It seems that mammalian phase II detoxification mechanisms make that dietary polyphenols are rapidly and effectively removed from the body, i.e. their concentration in the blood plasma hardly ever reaches levels high enough to have a possible effect on tumour growth. The polymethoxyflavones nobiletin and tangeretin, common constituents of Citrus peel, are better absorbed than polyhydroxy flavonoids, and maintain their biological activity for a longer period of time. The compounds are known to be substrates for the estrogen-converting cytochrome P450 enzymes CYP1A1 and CYP1B1, which are typically over-expressed in a range of tumour tissues. The enzymes catalyse regioselective hydroxylation and dealkylation of the polymethoxyflavones, resulting in reaction products that appear to inhibit cell proliferation via interference with the MAPK/ERK cell signalling pathway.

Toxicology in Vitro, Aug 1, 2018

Food and Chemical Toxicology, Sep 1, 2012

Recent studies have demonstrated cytochrome P450 CYP1-mediated metabolism and CYP1-enzyme inducti... more Recent studies have demonstrated cytochrome P450 CYP1-mediated metabolism and CYP1-enzyme induction by naturally occurring flavonoids in cancer cell line models. The arising metabolites often exhibit higher activity than the parent compound. In the present study we investigated the CYP1-mediated metabolism of the citrus polymethoxyflavone nobiletin by recombinant CYP1 enzymes and MCF7 breast adenocarcinoma cells. Incubation of nobiletin in MCF7 cells produced one main metabolite (NM1) resulting from O-demethylation in either A or B rings of the flavone moiety. Among the three CYP1 isoforms, CYP1A1 exhibited the highest rate of metabolism of nobiletin in recombinant CYP microsomal enzymes. The intracellular CYP1-mediated bioconversion of the flavone was reduced in the presence of the CYP1A1 and CYP1B1-selective inhibitors a-napthoflavone and acacetin. In addition nobiletin induced CYP1 enzyme activity, CYP1A1 protein and CYP1B1 mRNA levels in MCF7 cells at a concentration dependent manner. MTT assays in MCF7 cells further revealed that nobiletin exhibited significantly lower IC50 (44 lM) compared to cells treated with nobiletin and CYP1A1 inhibitor (69 lM). FACS analysis demonstrated cell a cycle block at G1 phase that was attenuated in the presence of CYP1A1 inhibitor. Taken together the data suggests that the dietary flavonoid nobiletin induces its own metabolism and in turn enhances its cytostatic effect in MCF7 breast adenocarcinoma cells, via CYP1A1 and CYP1B1 upregulation.

British Journal of Pharmacology, Mar 22, 2011

The mechanisms by which the dietary compound tangeretin has anticancer effects may include acting... more The mechanisms by which the dietary compound tangeretin has anticancer effects may include acting as a prodrug, forming an antiproliferative product in cancer cells. Here we show that tangeretin also inhibits cell cycle progression in hepatocytes and investigate the role of its primary metabolite 4′-hydroxy-5,6,7,8-tetramethoxyflavone (4′-OH-TMF) in this effect. EXPERIMENTAL APPROACH We used epidermal growth factor (EGF)-stimulated rat hepatocytes, with [ 3 H]-thymidine incorporation into DNA as an index of progression to S-phase of the cell cycle, and Western blots for phospho-proteins involved in the cell signalling cascade. KEY RESULTS Incubation of tangeretin with microsomes expressing CYP1A, or with hepatocytes, generated a primary product we identified as 4′-OH-TMF. Low micromolar concentrations of tangeretin or 4′-OH-TMF gave a concentration-dependent inhibition of EGF-stimulated progression to S-phase while having little effect on cell viability. To determine whether time for conversion of tangeretin to an active metabolite would enhance the inhibitory effect we used long pre-incubations; this reduced the inhibitory effect, in parallel with a reduction in the concentration of tangeretin. The EGF-stimulation of hepatocyte cell cycle progression requires signalling through Akt/mTOR/p70S6K kinase cascades. The tangeretin metabolite 4′-OH-TMF selectively inhibited S6K phosphorylation in the absence of significant inhibition of upstream Akt activity, suggesting an effect at the level of mTOR. CONCLUSIONS AND IMPLICATIONS Tangeretin and 4′-OH-TMF both inhibit cell cycle progression in primary hepatocytes. The inhibition of p70S6K phosphorylation by 4′-OH-TMF raises the possibility that inhibition of the mTOR pathway may contribute to the anticancer influence of a flavonoid-rich diet.

Cell cycle analysis of MDA-MB-468 cells co-treated with 10 μM eupatorin and 1.5 μM acacetin for 4... more Cell cycle analysis of MDA-MB-468 cells co-treated with 10 μM eupatorin and 1.5 μM acacetin for 48 hours. Histograms are one trace of three independent experiments. Cell cycle profile of MDA-MB-468 cells treated with 10 μM cirsiliol for 48 hours. The experiment was performed in duplicate.Copyright information:Taken from "Antiproliferative and cytostatic effects of the natural product eupatorin on MDA-MB-468 human breast cancer cells due to CYP1-mediated metabolism"http://breast-cancer-research.com/content/10/3/R39Breast Cancer Research : BCR 2008;10(3):R39-R39.Published online 2 May 2008PMCID:PMC2481486.

Typical high-pressure liquid chromatography (HPLC) traces of 20-minute incubation of CYP1 enzymes... more Typical high-pressure liquid chromatography (HPLC) traces of 20-minute incubation of CYP1 enzymes with eupatorin. Expansion of showing metabolites E2 and E3. Co-elution studies of eupatorin with cirsiliol. A 20-minute CYP1B1 incubate of eupatorin was spiked with cirsiliol (0.2 μM). Reaction mixtures contained eupatorin, NADPH (nicotinamide adenine dinucleotide phosphate), and recombinant microsomes purchased from Gentest Corporation (now part of BD Biosciences). Reactions were terminated by the addition of 1% acetic acid in methanol. HPLC trace of metabolism of eupatorin in MDA-MB-468 cells. Samples were analysed by HPLC using a UV detector at 350 nm. Experiments were performed in triplicate. A: absorption of light at wavelength 350 nm. AU: arbitrary units.Copyright information:Taken from "Antiproliferative and cytostatic effects of the natural product eupatorin on MDA-MB-468 human breast cancer cells due to CYP1-mediated metabolism"http://breast-cancer-...

Disappearance of eupatorin over time by CYP1 family enzymes. Formation of the metabolite cirsilio... more Disappearance of eupatorin over time by CYP1 family enzymes. Formation of the metabolite cirsiliol over a 20-minute time period. Experiments were performed in duplicate as described in Materials and methods. Error bars represent mean ± minimum or maximum values for n = 2 determinations.Copyright information:Taken from "Antiproliferative and cytostatic effects of the natural product eupatorin on MDA-MB-468 human breast cancer cells due to CYP1-mediated metabolism"http://breast-cancer-research.com/content/10/3/R39Breast Cancer Research : BCR 2008;10(3):R39-R39.Published online 2 May 2008PMCID:PMC2481486.

EROD activity of MDA-MB-468 and MCF-10A cells. Cells were seeded at a density of 5 × 10cells per ... more EROD activity of MDA-MB-468 and MCF-10A cells. Cells were seeded at a density of 5 × 10cells per millilitre in 24-well plates and left to grow for 48 hours. EROD activity was measured as described in Materials and methods. Error bars represent mean ± standard deviation for n = 4 determinations. Selective and inducible CYP1A and CYP1B1 expression in MDA-MB-468 cells. Lysates were probed with anti-CYP1A and anti-CYP1B1 antibodies from Gentest Corporation (now part of BD Biosciences) and Auvation Limited. Lane 1: Recombinant CYP1A1 (top, 0.2 μg) or CYP1B1 (bottom, 0.4 μg) used as positive control. Lane 2: MDA-MB-468 cells. Lane 3: MDA-MB-468 cells treated with 10 nM TCDD for 24 hours. Lane 4: MCF-10A cells. Experiments were performed in duplicate. EROD, ethoxyresorufin--deethylase; TCDD, 2,3,7,8-tetrachlorodibenzo--dioxin.Copyright information:Taken from "Antiproliferative and cytostatic effects of the natural product eupatorin on MDA-MB-468 human breast cancer ...

Cytotoxicity of eupatorin in MDA-MB-468 cells and MCF-10A cells. Decrease of eupatorin cytotoxici... more Cytotoxicity of eupatorin in MDA-MB-468 cells and MCF-10A cells. Decrease of eupatorin cytotoxicity in MDA-MB-468 cells after addition of acacetin. Cytotoxicity of acacetin in MDA-MB-468 cells and MCF-10A cells. Cytotoxicity of cirsiliol in MDA-MB-468 cells and MCF-10A cells. Cells were plated into 96-well plates and treated with 10to 100 μM eupatorin, acacetin, or cirsiliol (as described in Materials and methods) and allowed to grow for 96 hours. For the inhibition experiment, acacetin was used at a final concentration of 1.5 μM. Error bars represent mean ± standard deviation (SD) for n = 4 determinations. MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.Copyright information:Taken from "Antiproliferative and cytostatic effects of the natural product eupatorin on MDA-MB-468 human breast cancer cells due to CYP1-mediated metabolism"http://breast-cancer-research.com/content/10/3/R39Breast Cancer Research : BCR 2008;10(3):R39-R39.Published...

Vaccine, 2011

Phytochemistry Reviews, 2009

Breast Cancer Research, 2008

eClinicalMedicine, 2022

Background Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and midd... more Background Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based recombinant Newcastle disease virus vaccine expressing the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It's being developed by public sector manufacturers in Thailand, Vietnam, and Brazil; herein are initial results from Thailand. Methods This phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy males and non-pregnant females, aged 18–59 years and negative for SARS-CoV-2 antibodies, were eligible. Participants were randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 µg, 1 µg+CpG1018 (a toll-like receptor 9 agonist), 3 µg, 3 µg+CpG1018, 10 µg, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov (NCT04764422). Findings Between March 20 and April 23, 2021, 377 individuals were screened and 210 were enroled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (<63%), fatigue (<35%), headache (<32%), and myalgia (<32%). The proportion reporting a vaccine-related AE ranged from 5·7% to 17·1% among vaccine groups and was 2·9% in controls; there was no vaccine-related serious adverse event. The 10 µg formulation's immunogenicity ranked best, followed by 3 µg+CpG1018, 3 µg, 1 µg+CpG1018, and 1 µg formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122·23 international units per mL (IU/mL; 1 µg, 95% confidence interval (CI) 86·40–172·91) to 474·35 IU/mL (10 µg, 95% CI 320·90–701·19), with 93·9% to 100% of vaccine groups attaining a ≥ 4-fold increase over baseline. Interpretation NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 µg and 3 µg+CpG1018 formulations advanced to phase 2. Funding National Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA).

Flow cytometric DNA analysis of MDA-MB-468 and MCF-10A cells treated with 10 μM eupatorin. Percen... more Flow cytometric DNA analysis of MDA-MB-468 and MCF-10A cells treated with 10 μM eupatorin. Percentage of MDA-MB-468 cells in G, S+G/M, and sub-Gphases of the cell cycle. Cells were plated in 24-well plates and left to grow for 48 hours. Eupatorin was incubated with the cells for 30 and 48 hours, and 0.1% dimethylsulfoxide was used as a control. The cells were stained with propidium iodide and analysed using a Beckman Coulter flow cytometer as described in Materials and methods. Error bars represent mean ± standard deviation for n = 3 determinations.Copyright information:Taken from "Antiproliferative and cytostatic effects of the natural product eupatorin on MDA-MB-468 human breast cancer cells due to CYP1-mediated metabolism"http://breast-cancer-research.com/content/10/3/R39Breast Cancer Research : BCR 2008;10(3):R39-R39.Published online 2 May 2008PMCID:PMC2481486.