Assoc.Prof. Parinya Noisa

Year	Title	Journal
2019	Curcumin induces neural differentiation of human pluripotent embryonal carcinoma cells through the activation of autophagy Heebkaew N., Rujanapun N., Kunhorm P., Jaroonwitchawan T., Chaicharoenaudomrung N., Promjantuek W., Noisa P.	BioMed Research International
Abstract: Curcumin is a natural polyphenolic compound, isolated from Curcuma longa, and is an important ingredient of Asian foods. Curcumin has revealed its strong activities of anti-inflammatory, antioxidant, and anticancer. The efficient amount of curcumin could induce differentiation of stem cells and promoted the differentiation of glioma-initiating cells; however, the mechanisms underlying neural induction of curcumin have not yet been revealed. In this study, neural-inducing ability of curcumin was explored by using human pluripotent embryonal carcinoma cells, NTERA2 cells. The cells were induced toward neural lineage with curcumin and were compared with a standard neutralizing agent (retinoic acid). It was found that, after 14 days of the induction by curcumin, NTERA2 cells showed neuronal morphology and expressed neural-specific genes, including NeuroD, TUJ1, and PAX6. Importantly, curcumin activated neurogenesis of NTERA2 cells via the activation of autophagy, since autophagy-related genes, such as LC3, LAMP1, and ATG5, were upregulated along with the expression of neural genes. The inhibition of autophagy by chloroquine suppressed both autophagy and neural differentiation, highlighting the positive role of autophagy during neural differentiation. This autophagy-mediated neural differentiation of curcumin was found to be an ROS-dependent manner; curcumin induced ROS generation and suppressed antioxidant gene expression. Altogether, this study proposed the neural-inducing activity of curcumin via the regulation of autophagy within NTERA2 cells and underscored the health beneficial effects of curcumin for neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. © 2019 Nudjanad Heebkaew et al. Keyword: Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85061298824&doi=10.1155%2f2019%2f4378710&partnerID=40&md5=351b7392446b900b60e6ada6a4c82efa DOI: 10.1155/2019/4378710
2018	Roles of autophagy in controlling stem cell identity: a perspective of self-renewal and differentiation Sotthibundhu A., Promjuntuek W., Liu M., Shen S., Noisa P.	Cell and Tissue Research
Abstract: Autophagy is crucial for the removal of dysfunctional organelles and protein aggregates and for maintaining stem cell homeostasis, which includes self-renewal, cell differentiation and somatic reprogramming. Loss of self-renewal capacity and pluripotency is a major obstacle to stem cell-based therapies. It has been reported that autophagy regulates stem cells under biological stimuli, starvation, hypoxia, generation of reactive oxygen species (ROS) and cellular senescence. On the one hand, autophagy is shown to play roles in self-renewal by co-function with the ubiquitin-proteasome system (UPS) to promote pluripotency-associated proteins (NANOG, OCT4 and SOX2) in human embryonic stem cells (hESCs). On the other hand, autophagy activity acts as cell reprogramming processes that play an important role for clearance fate determination and upregulates neural and cardiac differentiation. Deregulation of autophagy triggers protein disorders such as neurodegenerative cardiac/muscle diseases and cancer. Therefore, understanding of the roles of the autophagy in stem cell renewal and differentiation may benefit therapeutic development for a range of human diseases. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Keyword: Autophagy; Brain development; Differentiation; Self-renewal; Stem cells Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85055084400&doi=10.1007%2fs00441-018-2829-7&partnerID=40&md5=53c0c563c5c5f2d330657fb3b494a994 DOI: 10.1007/s00441-018-2829-7
2018	Combined effects of curcumin and doxorubicin on cell death and cell migration of SH-SY5Y human neuroblastoma cells Namkaew J., Jaroonwitchawan T., Rujanapun N., Saelee J., Noisa P.	In Vitro Cellular and Developmental Biology - Animal
Abstract: Neuroblastoma is the most common cancer of the sympathetic nervous system in children. Here, the influences of curcumin on survival, apoptosis, migration, and its combined effects with doxorubicin were investigated in SH-SY5Y cells by cell survival assay, flow cytometry, migration assays, and RT-PCR. Curcumin inhibited SH-SY5Y cell growth and induced apoptosis in dose- and time-dependent manners. This apoptotic induction relied on the upregulation of p53 and p21. Moreover, the treatment of curcumin for 24 h significantly suppressed cell migration, together with the downregulation of matrix metalloproteinase-2 (MMP-2) and upregulation of tissue inhibitor of metalloproteinases-1 (TIMP-1). The combination of curcumin augmented the anticancer activity of doxorubicin and significantly induced apoptosis. Pretreatment with curcumin increased the fraction of doxorubicin-induced apoptotic cells from 21.76 ± 0.50 to 57.74 ± 2.68%. Co-treatment with doxorubicin plus curcumin further inhibited 3D tumor migration. Altogether, the results suggest that curcumin suppresses growth and migration of SH-SY5Y cells and enhances the anticancer activity of doxorubicin. The addition of curcumin to therapeutic regimens may be promising for the treatment of neuroblastomas if a number of problems related to its in vivo bioavailability can be resolved. [Figure not available: see fulltext.]. © 2018, The Society for In Vitro Biology. Keyword: Apoptosis; Curcumin; Doxorubicin; Migration; Neuroblastoma Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85052627077&doi=10.1007%2fs11626-018-0288-9&partnerID=40&md5=54c9462c0bdde2f4989b62f1177d90f1 DOI: 10.1007/s11626-018-0288-9
2018	Cordycepin induces apoptotic cell death of human brain cancer through the modulation of autophagy Chaicharoenaudomrung N., Jaroonwitchawan T., Noisa P.	Toxicology in Vitro
Abstract: Brain cancer, in particular neuroblastoma and glioblastoma, is a global challenge to human health. Cordycepin, extracted from Cordyceps ssp., has been revealed as a strong anticancer agent through several ways; however, the mechanism, by which cordycepin counteracts brain cancers, is still poorly understood. In this study, the underlying mechanisms of cordycepin against human brain cancer cells were explored. SH-SY5Y and U251 cells were being a model to represent human neuroblastoma and glioblastoma, respectively. Here, it was found that cordycepin inhibited cell growth, and induced apoptosis in a dose-dependent manner in both SH-SY5Y and U-251 cell lines. The expression of pro-apoptotic genes, including P53, BAX, Caspase-3, and Caspase-9, were upregulated, whereas the expression of anti-apoptotic gene, BCL-2, was suppressed. Besides, cordycepin induced the generation of reactive oxygen species (ROS) along with the suppression of antioxidant genes, including GPX, SOD, and Catalase. Importantly, cordycepin was shown to involve in the activation of autophagy, which was evidenced by the increment of LC3I/II. The combination of cordycepin with chloroquine, an autophagy inhibitor, further inhibited the growth, and enhanced the death of brain cancer cells. Altogether, this finding suggested that cordycepin induced apoptosis of human brain cancer cells through mitochondrial-mediated intrinsic pathway and the modulation of autophagy. Therefore, cordycepin could be a promising candidate for the development of anticancer drugs targeting human brain cancers. © 2017 Elsevier Ltd Keyword: Apoptosis; Autophagy; Brain cancer; Cordycepin Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85030855378&doi=10.1016%2fj.tiv.2017.10.002&partnerID=40&md5=4f19f4a99980276c1533003e1062246d DOI: 10.1016/j.tiv.2017.10.002
2018	Aza-BODIPY based polymeric nanoparticles for cancer cell imaging Chansaenpak K., Tanjindaprateep S., Chaicharoenaudomrung N., Weeranantanapan O., Noisa P., Kamkaew A.	RSC Advances
Abstract: Near infrared (NIR) fluorescent dyes that are widely used for cancer imaging usually suffer from their hydrophobicity. To overcome this problem, a water-suspendable and biodegradable NIR-light-activating aza-BODIPY (AZB-NO2) encapsulated in polymeric nanoparticles was prepared as a new class of deep-tissue imaging agent. AZB-NO2 possesses an intense, broad NIR absorption band (600-800 nm) with a remarkably high fluorescent quantum yield. After being encapsulated with a biodegradable polycaprolactone (PCL) and a Kolliphor P188 surfactant by emulsification-solvent evaporation method, the AZB-NO2 formed a spherical shape as observed in scanning electron micrographs (SEM) with a hydrodynamic average size of 201 nm (average PDI = 0.185). The results from transmission electron micrographs (TEM) and energy dispersive X-ray spectroscopy (EDS) elemental mapping indicated that the AZB-NO2 homogeneously distributed in the polymeric shell. UV-visible-NIR and fluorescence spectra of the obtained nanoparticles, AZB-NO2@PCL, revealed that the nanoparticles prepared by using 0.8 mg dye loading exhibited the highest fluorescence quantum yield. These nanoparticles were then applied for fluorescence imaging in human glioblastoma cell line (U-251). After the cells were exposed to AZB-NO2@PCL, the materials appeared to be localized inside U-251 cells within 3 h and the fluorescence signal enhanced along with the increased incubation times. Moreover, 3D cell culture was used in this study to mimic in vivo tumor environments. The AZB-NO2@PCL exhibited bright fluorescence from U-251 cells inside 3D Ca-alginate scaffolds after 24 h incubation. Our study successfully demonstrated that the encapsulation of hydrophobic aza-BODIPY dye could enhance the water-suspendability of the dye yielding biocompatible nanoparticles efficiently used in cancer cell imaging applications. © The Royal Society of Chemistry. Keyword: Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85057714694&doi=10.1039%2fc8ra08145j&partnerID=40&md5=f36bb4599683c3a9b3b315807c94548b DOI: 10.1039/c8ra08145j
2017	Inhibition of WNT signaling reduces differentiation and induces sensitivity to doxorubicin in human malignant neuroblastoma SH-SY5Y cells Suebsoonthron J., Jaroonwitchawan T., Yamabhai M., Noisa P.	Anti-Cancer Drugs
Abstract: Neuroblastoma is one of the most common cancers in infancy, arising from the neuroblasts during embryonic development. This cancer is difficult to treat and resistance to chemotherapy is often found; therefore, clinical trials of novel therapeutic approaches, such as targeted-cancer signaling, could be an alternative for a better treatment. WNT signaling plays significant roles in the survival, proliferation, and differentiation of human neuroblastoma. In this report, WNT signaling of a malignant human neuroblastoma cell line, SH-SY5Y cells, was inhibited by XAV939, a specific inhibitor of the Tankyrase enzyme. XAV939 treatment led to the reduction of β-catenin within the cells, confirming its inhibitory effect of WNT. The inhibition of WNT signaling by XAV939 did not affect cell morphology, survival, and proliferation; however, the differentiation and sensitivity to anticancer drugs of human neuroblastoma cells were altered. The treatment of XAV939 resulted in the downregulation of mature neuronal markers, including β-tubulin III, PHOX2A, and PHOX2B, whereas neural progenitor markers (PAX6, TFAP2α, and SLUG) were upregulated. In addition, the combination of XAV939 significantly enhanced the sensitivity of SH-SY5Y and IMR-32 cells to doxorubicin in both 2D and 3D culture systems. Microarray gene expression profiling suggested numbers of candidate target genes of WNT inhibition by XAV939, in particular, p21, p53, ubiquitin C, ZBED8, MDM2, CASP3, and FZD1, and this explained the enhanced sensitivity of SH-SY5Y cells to doxorubicin. Altogether, these results proposed that the altered differentiation of human malignant neuroblastoma cells by inhibiting WNT signaling sensitized the cells to anticancer drugs. This approach could thus serve as an effective treatment option for aggressive brain malignancy. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. Keyword: drug sensitivity; human neuroblastoma; SH-SY5Y cells; WNT signaling Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85014008673&doi=10.1097%2fCAD.0000000000000478&partnerID=40&md5=7a58cf140a83e763cb83e8c0770601ae DOI: 10.1097/CAD.0000000000000478
2017	Curcumin attenuates paraquat-induced cell death in human neuroblastoma cells through modulating oxidative stress and autophagy Jaroonwitchawan T., Chaicharoenaudomrung N., Namkaew J., Noisa P.	Neuroscience Letters
Abstract: Paraquat is a neurotoxic agent, and oxidative stress plays an important role in neuronal cell death after paraquat exposure. In this study, we assessed the neuroprotective effect of curcumin against paraquat and explored the underlying mechanisms of curcumin in vitro. Curcumin treatment prevented paraquat-induced reactive oxygen species (ROS) and apoptotic cell death. Curcumin also exerted a neuroprotective effect by increasing the expression of anti-apoptotic and antioxidant genes. The pretreatment of curcumin significantly decreased gene expression and protein production of amyloid precursor protein. The activation of autophagy process was found defective in paraquat-induced cells, indicated by the accumulation and reduction of LC3I/II. Noteworthy, curcumin restored LC3I/II expression after the pretreatment. Collectively, curcumin demonstrated as a prominent suppressor of ROS, and could reverse autophagy induction in SH-SY5Y cells. The consequences of this were the reduction of APP production and prevention of SH-SY5Y cells from apoptosis. Altogether, curcumin potentially serves as a therapeutic agent of neurodegenerative diseases, associated with ROS overproduction and autophagy dysfunction. © 2016 Elsevier Ireland Ltd Keyword: Alzheimer's disease; Autophagy; Curcumin; Oxidative stress Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85002168925&doi=10.1016%2fj.neulet.2016.10.050&partnerID=40&md5=558b6afc68365eb1b3753fdb80452e4f DOI: 10.1016/j.neulet.2016.10.050
2016	Inhibition of FGF signaling accelerates neural crest cell differentiation of human pluripotent stem cells Jaroonwitchawan T., Muangchan P., Noisa P.	Biochemical and Biophysical Research Communications
Abstract: Neural crest (NC) is a transient population, arising during embryonic development and capable of differentiating into various somatic cells. The defects of neural crest development leads to neurocristopathy. Several signaling pathways were revealed their significance in NC cell specification. Fibroblast growth factor (FGF) is recognized as an important signaling during NC development, for instance Xenopus and avian; however, its contributions in human species are remained elusive. Here we used human pluripotent stem cells (hPSCs) to investigate the consequences of FGF inhibition during NC cell differentiation. The specific-FGF receptor inhibitor, SU5402, was used in this investigation. The inhibition of FGF did not found to affect the proliferation or death of hPSC-derived NC cells, but promoted hPSCs to commit NC cell fate. NC-specific genes, including PAX3, SLUG, and TWIST1, were highly upregulated, while hPSC genes, such as OCT4, and E-CAD, rapidly reduced upon FGF signaling blockage. Noteworthy, TFAP-2α, a marker of migratory NC cells, abundantly presented in SU5402-induced cells. This accelerated NC cell differentiation could be due to the activation of Notch signaling upon the blockage of ERK1/2 phosphorylation, since NICD was increased by SU5402. Altogether, this study proposed the contributions of FGF signaling in controlling human NC cell differentiation from hPSCs, the crosstalk between FGF and Notch, and might imply to the influences of FGF signaling in neurocristophatic diseases. © 2016 Elsevier Inc. Keyword: FGF signaling; Human pluripotent stem cells; Neural crest; SU5402 Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85001085836&doi=10.1016%2fj.bbrc.2016.10.147&partnerID=40&md5=603b27b2b97968dad4e16e36e7f843a6 DOI: 10.1016/j.bbrc.2016.10.147
2016	Development of Gonadotropin-Releasing Hormone-Secreting Neurons from Human Pluripotent Stem Cells Lund C., Pulli K., Yellapragada V., Giacobini P., Lundin K., Vuoristo S., Tuuri T., Noisa P., Raivio T.	Stem Cell Reports
Abstract: Gonadotropin-releasing hormone (GnRH) neurons regulate human puberty and reproduction. Modeling their development and function in vitro would be of interest for both basic research and clinical translation. Here, we report a three-step protocol to differentiate human pluripotent stem cells (hPSCs) into GnRH-secreting neurons. Firstly, hPSCs were differentiated to FOXG1, EMX2, and PAX6 expressing anterior neural progenitor cells (NPCs) by dual SMAD inhibition. Secondly, NPCs were treated for 10 days with FGF8, which is a key ligand implicated in GnRH neuron ontogeny, and finally, the cells were matured with Notch inhibitor to bipolar TUJ1-positive neurons that robustly expressed GNRH1 and secreted GnRH decapeptide into the culture medium. The protocol was reproducible both in human embryonic stem cells and induced pluripotent stem cells, and thus provides a translational tool for investigating the mechanisms of human puberty and its disorders. © 2016 The Author(s) Keyword: GnRH; gonadotropin-releasing hormone; human embryonic stem cells; human pluripotent stem cells; hypogonadotropic hypogonadism; induced pluripotent stem cells; Kallmann syndrome; puberty Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84978924548&doi=10.1016%2fj.stemcr.2016.06.007&partnerID=40&md5=d51942b475575edac0537bd338cf56b2 DOI: 10.1016/j.stemcr.2016.06.007
2016	Human Embryonic Stem Cells: A Model for the Study of Neural Development and Neurological Diseases Prajumwongs P., Weeranantanapan O., Jaroonwitchawan T., Noisa P.	Stem Cells International
Abstract: Although the mechanism of neurogenesis has been well documented in other organisms, there might be fundamental differences between human and those species referring to species-specific context. Based on principles learned from other systems, it is found that the signaling pathways required for neural induction and specification of human embryonic stem cells (hESCs) recapitulated those in the early embryo development in vivo at certain degree. This underscores the usefulness of hESCs in understanding early human neural development and reinforces the need to integrate the principles of developmental biology and hESC biology for an efficient neural differentiation. © 2016 Piya Prajumwongs et al. Keyword: Scopus Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84973162923&doi=10.1155%2f2016%2f2958210&partnerID=40&md5=6976a66091ca5c43d2c87e9ed5a97f48 DOI: 10.1155/2016/2958210