Publications by authors named "Sermkiat Tanuchit"

7 Publications

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Synergistic Genotoxic Effects and Modulation of Cell Cycle by Ginger Ethanolic Extracts in Adjunct to Doxorubicin in Human Lymphocytes In Vitro.

J Med Assoc Thai 2015 Apr;98 Suppl 3:S101-9

Background: Several natural phytochemicals are increasingly used, as an adjunct to chemotherapy, to reduce drug adverse effects. Zingiber officinale rhizome (ginger) product has been reported to be effective against nausea and vomiting in patients receiving emetogenic chemotherapy such as cisplatin/doxorubicin (DXR). In addition, its ethanolic extract of Zingiber officinale rhizome (EEZOR) has been reported to possess anticarcinogenic properties. However, the mechanism for anticancer activity of ginger especially when used in combination with chemotherapy has not well elucidated, one of its possible mechanisms might involve its genotoxicity.

Objective: To investigate genotoxic and cytotoxic potentials of EEZOR alone and EEZOR pretreatments followed by 0.1 mcg/ ml DXR, a genotoxic chemotherapeutic agent in human lymphocytes by sister chromatid exchange (SCE) assay in vitro. The effect on cell cycle kinetics was also explored.

Material And Method: Human lymphocytes were treated with EEZOR alone at 25-500 mcg/ml and EEZOR pretreated at 12.5-200 mcg/ml followed by 0.1 mcg/ml DXR. SCE levels and cell cycle kinetics were evaluated.

Results: EEZOR significantly induced biphasic SCE at 50 and 400 mcg/ml (p < 0.05). However, cytotoxicity manifested at 500 mcg/ml. All EEZOR pretreatments at 12.5, 25, 50, and 100 mcg/ml, except at 200 mcg/ml, prior to DXR, moderately enhanced DXR-induced genotoxicity by 1.3 times (p < 0.05). Both EEZOR alone and EEZOR prior to DXR at certain concentrations delayed cell cycle.

Conclusion: At specific doses, EEZOR could induce genotoxicity and in pretreatments could moderately enhance DXR-induced genotoxicity and delay cell cycle. This finding suggests that dosage use of EEZOR needs to be adjusted for long-term safety. In addition, EEZOR in adjunct to DXM might have potential benefits not only as an emetic agent but also in chemotherapy. Further in vivo animal and human studies to support this evidence is essentially needed.
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April 2015

In vitro enhancement of doxorubicin genotoxic activities and interference with cell cycle delay by Plumbago indica root ethanolic extract in human lymphocytes.

J Med Assoc Thai 2015 Mar;98 Suppl 2:S38-44

Background: Combinations of modern medicines with herbal medicines are being developedfor more effectiveness. Data on the safety and drug-herb interactions are needed to be clarified. Ethanolic extract of Plumbago indica root (EEPIR) is medicinally usedfor cancer treatment in Asian traditional medicine. However its mechanism of action is still inconclusive. Our previous study demonstrated that EEPIR was genotoxic and induced cell cycle delay in human lymphocytes in vitro.

Objective: To investigate genotoxic potency and interference with cell cycle of EEPIR in combination with doxorubicin (DXR), a standard chemotherapeutic agent, in human lymphocytes by in vitro sister chromatid exchange (SCE) assay.

Material And Method: Human lymphocytes were pretreated with EEPIR at 6.25-100 mcg/mlfollowed by DXR (0.1 mcg/ml). SCE levels and cell cycle kinetics were evaluated.

Results: EEPIR pretreatments (6.5-50 mcg/ml) significantly enhanced genetic damage induced by DXR (p<0. 05). Delaying of the cell cycle was detected and related to EEPIR concentration. EEPIR at 100 mcg/ml, on the contrary, did not enhance DXR-induced genotoxicity but tended to lower genotoxicity compared to DXR treatment alone. It significantly delayed cell cycle the most (p<0.05).

Conclusion: EEPIR pretreatments at proper doses enhanced genotoxic damage induced by DXR in human lymphocytes. Delaying cell cycle by EEPIR could lower that potency. Usage of EEPIR, therefore, should be adjusted for safety. Combination of EEPIR with DXR might be usefulfor more efficient cancer treatment with less DXR toxicity. Further in vivo study is needed to support this in vitro evidence.
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March 2015

A Comparison of Cefditoren Pivoxil 8-12 mg/kg/day and Cefditoren Pivoxil 16-20 mg/kg/day in Treatment of Children With Acute Presumed Bacterial Rhinosinusitis: A Prospective, Randomized, Investigator-Blinded, Parallel-Group Study.

Clin Exp Otorhinolaryngol 2015 Jun 13;8(2):129-35. Epub 2015 May 13.

Research Office, Faculty of Medicine, Thammasat University, Klong Luang, Thailand.

Objectives: Cefditoren pivoxil (CDT) has been used in the treatment of rhinosinusitis. However, little is known about the efficacy of this drug at low and high doses. This study was to compare the efficacy and safety of low dose (8-12 mg/kg/day) and high dose (16-20 mg/kg/day) CDT in the treatment of children with uncomplicated acute rhinosinusitis (ARS).

Methods: This investigation was a randomized, investigator-blinded, and parallel study, conducted in patients (aged 1-15 years) with a clinical diagnosis of uncomplicated ARS. Two groups of patients randomly received low dose or high dose CDT for 14 days. Patients' symptoms were assessed quantitatively using a quantitative symptom score (the S5 score). The changes in sinus symptoms and adverse events were provided by patients and their parents/caregivers. The response rate and adverse effects were evaluated at days 7 and 14. The relapse rate was recorded at days 21 and 28. The recurrences of sinus symptoms at day 60 were also assessed.

Results: One hundred forty patients were recruited and randomized; 72 received low dose CDT (group I) and 68 received high dose CDT (group II). There were no significant differences in demographic data including sex, age, presenting symptoms, medical history, and X-ray findings between two groups. The responses rate at day 14 in groups I and II were 95.5% and 95.4%, respectively (P>0.99). There were no significant differences between groups in relapse rate at day 28 and no recurrence at day 60 in either group. The most common treatment-related adverse events were diarrhea (4.2% in group I vs. 2.9% in group II) and vomiting (2.8% in group I vs. 10.3% in group II). There was no statistically significant difference in adverse events between groups.

Conclusion: Both low and high doses regimens of CDT appeared a similar clinical outcome for treatment in uncomplicated ARS in pediatric patients.
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http://dx.doi.org/10.3342/ceo.2015.8.2.129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451537PMC
June 2015

Growth arrest and apoptosis via caspase activation of dioscoreanone in human non-small-cell lung cancer A549 cells.

BMC Complement Altern Med 2014 Oct 24;14:413. Epub 2014 Oct 24.

Division of Biochemistry, Department of Preclinical Science, Faculty of Medicine, Thammasat University, Rangsit Campus, Khlong Luang, Pathum Thani 12120, Thailand.

Background: Dioscoreanone (DN) isolated from Dioscorea membranacea Pierre has been reported to exert potent cytotoxic effects against particular types of cancer. The present study was carried out to investigate the cytotoxicity of DN against a panel of different human lung cancer cell lines. The study further examined the underlying mechanisms of its anticancer activity in the human lung adenocarcinoma cell line A549.

Methods: Antiproliferative effects of DN were determined by SRB and CFSE assays. The effect of DN on cell cycle distribution was assessed by flow cytometric analysis. Apoptotic effects of DN were determined by sub-G1 quantitation and Annexin V-FITC/PI flow cytometric analyses, as well as by changes in caspase-3 activity and relative levels of Bax and Bcl-2 mRNA.

Results: DN exerted antiproliferative and cytotoxic effects on all three subtypes of non-small cell lung cancer (NSCLC) cells, but not on small cell lung cancer (SCLC) cells and normal lung fibroblasts. DN slowed down the cell division and arrested the cell cycle at the G2/M phase in treated A549 cells, leading to a dose- and time- dependent increase of the sub-G1 population (apoptotic cells). Consistently, early apoptotic cells (AnnexinV +/PI-) were detected in those cells that were treated for 24 h and increased progressively over time. Moreover, the highest activity of caspase-3 in DN-treated A549 cells was detected within the first 24 h, and pretreatment with the general caspase inhibitor z-VAD-fmk completely abolished such activity and also DN-induced apoptosis in a dose-dependent manner. Additionally, DN increased the Bax/Bcl-2 ratio in treated A549 cells with time, indicating its induction of apoptosis via the mitochondrial pathway.

Conclusions: This study reveals for the first time that the anticancer activity of DN was induced through regulation of the Bcl-2 family protein-mediated mitochondrial pathway and the subsequent caspase-3 activation in A549 cancer cells, thus supporting its potential role as a natural apoptosis-inducing agent for NSCLC.
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http://dx.doi.org/10.1186/1472-6882-14-413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286926PMC
October 2014

Genotoxicity and interference with cell cycle activities by an ethanolic extract from Thai Plumbago indica roots in human lymphocytes in vitro.

Asian Pac J Cancer Prev 2013 ;14(4):2487-90

Department of Preclinical Science, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.

In Thai traditional medicine, Plumbago indica or Jetamul-Pleung-Dang in Thai is known to have health benefit especially for anti-inflammatory, antibacterial, and antitumor activities. However, the mechanisms of its action are still uncertain. One of which might be genotoxic effects. In the present study, we investigated the genotoxicity of an ethanolic extract of Plumbago indica root (EEPIR) by sister chromatid exchange (SCE) assay in human lymphocytes. Results have shown that all treatments with EEPIR (12.5-100 μg/ml) could induce cell cycle delay as shown by significant increase in the number of metaphase cells in the first cell cycle but neither in the second nor the third cell cycle. Only at concentrations of 25, 50, and 100 μg/ml were SCE levels significantly increased above that of the control (p<0.05) . EEPIR at a concentration of 500 μg/ml induced cell death as few mitotic cells were shown. Accordingly, EEPIR (25-100 μg/ml) is genotoxic in human lymphocytes and cytotoxic at concentrations of ≥ 500 μg/ml in vitro. Therefore, these activities of the EEPIR could serve its potential therapeutic effects, especially as an anticancer agent. Further study of EEPIR in vivo is now needed to support this in vitro evidence.
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http://dx.doi.org/10.7314/apjcp.2013.14.4.2487DOI Listing
October 2013

Antigenotoxic activity of Thai Sangyod red rice extracts against a chemotherapeutic agent, doxorubicin, in human lymphocytes by sister chromatid exchange (SCE) assay in vitro.

J Med Assoc Thai 2012 Jan;95 Suppl 1:S109-14

Division of Biochemistry, Preclinical Science Department, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.

Background: Nowadays, anticarcinogenic potential of pigmented brown rice and rice bran varieties have been increasingly stated. However, their mechanisms of action are still inconclusive. One of which might be their antigenotoxic activity that no study in human cells was reported before.

Objective: To evaluate the antigenotoxic activities of Thai Sangyod red rice extracts against a chemotherapeutic agent, doxorubicin, by sister chromatid exchange (SCE) assay in human lymphocytes in vitro.

Material And Method: Two fractions of water-soluble of Sangyod rice extracts were used: (i) the washed water extract of brown rice (WWBR) and (ii) the water extract of rice bran (WERB). Human lymphocytes were pretreated with each extracts at concentrations of 6.2, 12.5, 25, 50 and 100 microg/ml for 2 h followed by a genotoxic agent, doxorubicin (DXR) (0.1 microg/ml) for 2 h. SCE level, mitotic index (MI) and proliferation index (PI) were evaluated. Statistical analysis by Dunnett's t-test was performed.

Results: The results indicated that the pretreatment of WERB fraction only at concentration of 6.2 microg/ml could significantly decrease SCE level as compared to that of the DXR treated alone (p < 0.05). On the other hand, WERB fraction at other concentrations and all WWBR pretreatments could not. In addition, there was no significant difference in MI and PI levels between all pretreated extracts as compared to the DXR treated alone.

Conclusion: Our data revealed that WERB pretreatment only at specific low concentration of 6.2 microg/ml possessed the antigenotoxic potential against genotoxic damage but not anticytotoxic induced by DXR. Further work is still needed to clarify more the antigenotoxic and anticytotoxic potentials from other fractions of Sangyod rice extracts.
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January 2012

Determination of phenolic compounds, flavonoids, and antioxidant activities in water extracts of Thai red and white rice cultivars.

J Med Assoc Thai 2010 Dec;93 Suppl 7:S83-91

Department of Preclinical Science, Faculty of Medicine, Thammasat University, Rangsit Campus, KlongLuang, Pathumthani, Thailand.

Background: Free radical-induced oxidative stress damages cellular components leading to many human diseases. Plant-derived antioxidant compounds have become a profitable alternative to prevent oxidative stress in cells.

Objective: To determine and compare total phenolic and flavonoid contents as well as antioxidant activity using both chemical and cell assays in the water extracts of brown rice and rice bran from two Thai rice cultivars: Sangyod, a red pigmented rice typically grown in Southern Thailand and Dawk Mali 105, a commercial white-colored rice.

Material And Method: All the rice water extracts were analyzed for their total phenolic and flavonoid contents using the colorimetric assays, as well as for their antioxidant activity through two chemical assays: DPPH radical-scavenging and inhibition of lipid peroxidation assays, as well as through cell-based assays: scavenging capacity of intracellular ROS in HL60 cells using the fluorescent DCF and the NBT reduction.

Results: The two chemical assays detected free radical scavenging and free radical chain breaking activities in all the rice extracts with EC50 values ranging from 26 to 357 microg/ml. Moreover, the cell-based assays detected ROS scavenging activities of these extracts with EC50 values in the range of 0.6-5 mg/ml. All these assays indicated that the water extracts of Sangyod exerted significantly higher antioxidant activity than those of Dawk Mali 105, which exhibited only moderate to low activity. Furthermore, high levels of antioxidant activity of the water extracts of Sangyod were closely correlated to their flavonoid and phenolic contents, which were approximately 2.5 and 3 times higher, respectively, than those of Dawk Mali 105.

Conclusion: These findings suggest that water extracts from colored brown rice or colored rice bran can be promising sources of potential natural antioxidants.
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http://dx.doi.org/10.1055/s-0030-1264431DOI Listing
December 2010