Browsing by Author "Nahathai Dukaew"

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    Enhancement of Radiosensitivity by Eurycomalactone in Human NSCLC Cells through G2/M Cell Cycle Arrest and Delayed DNA Double-Strand Break Repair
    (2020-03-27) Nahathai Dukaew; Teruaki Konishi; Kongthawat Chairatvit; Narongchai Autsavapromporn; Noppamas Soonthornchareonnon; Ariyaphong Wongnoppavich; Institute for Quantum Life Science; National Institute of Radiological Sciences Chiba; Mahidol University; Chiang Mai University
    © 2020 Cognizant, LLC. Radiotherapy (RT) is an important treatment for non-small cell lung cancer (NSCLC). However, the major obstacles to successful RT include the low radiosensitivity of cancer cells and the restricted radiation dose, which is given without damaging normal tissues. Therefore, the sensitizer that increases RT efficacy without dose escalation will be beneficial for NSCLC treatment. Eurycomalactone (ECL), an active quassinoid isolated from Eurycoma longifolia Jack, has been demonstrated to possess anticancer activity. In this study, we aimed to investigate the effect of ECL on sensitizing NSCLC cells to X-radiation (X-ray) as well as the underlying mechanisms. The results showed that ECL exhibited selective cytotoxicity against the NSCLC cells A549 and COR-L23 compared to the normal lung fibroblast. Clonogenic survival results indicated that ECL treatment prior to irradiation synergistically decreased the A549 and COR-L23 colony number. ECL treatment reduced the expression of cyclin B1 and CDK1/2 leading to induce cell cycle arrest at the radiosensitive G2/M phase. Moreover, ECL markedly delayed the repair of radiation-induced DNA double-strand breaks (DSBs). In A549 cells, pretreatment with ECL not only delayed the resolving of radiation-induced ?-H2AX foci but also blocked the formation of 53BP1 foci at the DSB sites. In addition, ECL pretreatment attenuated the expression of DNA repair proteins Ku-80 and KDM4D in both NSCLC cells. Consequently, these effects led to an increase in apoptosis in irradiated cells. Thus, ECL radiosensitized the NSCLC cells to X-ray via G2/M arrest induction and delayed the repair of X-ray-induced DSBs. This study offers a great potential for ECL as an alternative safer radiosensitizer for increasing the RT efficiency against NSCLC.
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    Inactivation of AKT/NF-κB signaling by eurycomalactone decreases human NSCLC cell viability and improves the chemosensitivity to cisplatin
    (2020-10-01) Nahathai Dukaew; Kongthawat Chairatvit; Pornsiri Pitchakarn; Arisa Imsumran; Jirarat Karinchai; Wirote Tuntiwechapikul; Ariyaphong Wongnoppavich; Mahidol University; Chiang Mai University; Graduate/PhD Degree Program in Biochemistry
    © This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License. The high activation of protein kinase B (AKT)/nuclear factor-κB (NF-κB) signaling has often been associated with the induction of non-small cell lung cancer (NSCLC) cell survival and resistance to cisplatin, which is one of the most widely used chemotherapeutic drugs in the treatment of NSCLC. The inhibition of AKT/NF-κB can potentially be used as a molecular target for cancer therapy. Eurycomalactone (ECL), a quassinoid from Eurycoma longi- folia Jack, has previously been revealed to exhibit strong cytotoxic activity against the human NSCLC A549 cell line, and can inhibit NF-κB activity in TNF-α-activated 293 cells stably transfected with an NF-κB luciferase reporter. The present study was the first to investigate whether ECL inhibits the activation of AKT/NF-κB signaling, induces apoptosis and enhances chemosensitivity to cisplatin in human NSCLC cells. The anticancer activity of ECL was evaluated in two NSCLC cell lines, A549 and Calu-1. ECL decreased the viability and colony formation ability of both cell lines by inducing cell cycle arrest and apoptosis through the activation of pro-apoptotic caspase-3 and poly (ADP-ribose) polymerase, as well as the reduction of anti-apoptotic proteins Bcl-xL and survivin. In addition, ECL treatment suppressed the levels of AKT (phospho Ser473) and NF-κB (phospho Ser536). Notably, ECL significantly enhanced cisplatin sensitivity in both assessed NSCLC cell lines. The combination treatment of cisplatin and ECL promoted cell apoptosis more effectively than cisplatin alone, as revealed by the increased cleaved caspase-3, but decreased Bcl-xL and survivin levels. Exposure to cisplatin alone induced the levels of phosphorylated-AKT and phosphorylated-NF-κB, whereas co-treatment with ECL inhibited the cisplatin-induced phosphorylation of AKT and NF-κB, leading to an increased sensitization effect on cisplatin-induced apoptosis. In conclusion, ECL exhibited an anticancer effect and sensitized NSCLC cells to cisplatin through the inactivation of AKT/NF-κB signaling. This finding provides a rationale for the combined use of chemotherapy drugs with ECL to improve their efficacy in NSCLC treatment.
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    Safety and bioactivity assessment of aqueous extract of Thai Henna (Lawsonia inermis Linn.) Leaf
    (2021-01-01) Orawan Khantamat; Nahathai Dukaew; Jirarat Karinchai; Teera Chewonarin; Pornsiri Pitchakarn; Piya Temviriyanukul; Mahidol University; Chiang Mai University
    The worldwide demand for a natural dye by the cosmetic and food industry has recently gained interest. To provide scientific data supporting the usage of Thai henna leaf as a natural colorant, the phytochemical constituents, safety, and bioactivity of aqueous extract of the henna leaf by autoclave (HAE) and hot water (HHE) were determined. HAE contained a higher amount of total phenolic and flavonoid contents than HHE. The major constituents in both extracts were ferulic acid, gallic acid, and luteolin. The extracts displayed no marked mutagenic activity both in vitro and in vivo mammalian-like biotransformation. HAE and HHE also exhibited non-cytotoxicity to human immortalized keratinocyte cells (HaCaT), peripheral blood mononuclear cells (PBMCs), and murine macrophage RAW 264.7 cell line with IC20 and IC50 > 200 μg/ml. The extracts exhibited antioxidant and anti-inflammatory activity as evidenced by significant scavenging of ABTS and DPPH radicals and decreasing NO levels in LPS-induced RAW 264.7 cells. The antioxidant and anti-inflammatory properties of the extracts might be attributed to their phenolic and flavonoid contents. In conclusion, the traditional use of henna as a natural dye appears not to exert toxic effects and seems biosecure. Regarding safety, antioxidant, and anti-inflammatory properties, the aqueous extract of Thai henna leaf might thus serve as a readily available source for utilization in commercial health industries.
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    Upregulation of maspin expression in human cervical carcinoma cells by transforming growth factor β1 through the convergence of Smad and non-Smad signaling pathways
    (2017-05-01) Ariyaphong Wongnoppavich; Nahathai Dukaew; Sirinthip Choonate; Kongthawat Chairatvit; Chiang Mai University; Mahidol University
    © 2017, Spandidos Publications. All rights reserved. Mammary serine protease inhibitor (maspin), encoded by the serpin family B member 5 gene, serves as a tumor suppressor through the inhibition of cancer cell invasion and metastasis. Paradoxically, maspin levels are upregulated in a number of types of malignant cells. Therefore, the regulation of maspin expression may depend on the genetic or epigenetic background and the specific microenvironment of carcinoma cells. In the present study, it was demonstrated that transforming growth factorβ1 (TGF-β1) induced maspin expression at the transcript and protein levels in the human cervical carcinoma HeLa and human oral squamous carcinoma HSC4 cell lines. The inhibition of the mothers against decapentaplegic homolog (Smad)-dependent pathway by a Smad3-specific inhibitor suppressed maspin induction by TGF-β1 in HeLa cells. Inhibition of the non-Smad pathway by pretreatment with the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor U0126, or the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB202190, attenuated the effect of TGF-β1 on maspin upregulation, whereas pretreatment with pyrrolidine dithiocarbamate (a nuclear factorκB inhibitor), wortmannin (a phosphoinositide 3-kinase inhibitor) or SP600125 (a c-Jun N-terminal kinase inhibitor) did not. Notably, none of these inhibitors eliminated the TGF-β1-induced phosphorylation of Smad2. In addition, mutations at p53-binding sites in the maspin promoter suppressed TGF-β1-induced maspin expression, indicating the necessity of intact p53-binding sites on the maspin promoter. In summary, the induction of maspin expression in HeLa cells requires the convergence of TGF-β1-induced Smad and non-Smad signaling pathways, in which the latter acts via the intermediate signaling molecules MEK1/2 and p38 MAPK.