Souren Paul

@umn.edu

SENIOR RESEARCHER (RESEARCHER 5)
University of Minnesota



              

https://researchid.co/paulx215

EDUCATION

MSc in Botany with Plant Physiology and Biochemistry Specialization from The University of Burdwan, West Bengal, India
PhD in Biotechnology from Daegu University, Republic of Korea
Post-Doctoral: 2013-2016, Daegu University, Republic of Korea
Post-Dcotoral: 2016-2021, University of Minnesota, United States

RESEARCH, TEACHING, or OTHER INTERESTS

Agricultural and Biological Sciences, Biochemistry, Genetics and Molecular Biology, Cancer Research, Cell Biology

26

Scopus Publications

Scopus Publications

  • Centromere defects, chromosome instability, and cGAS-STING activation in systemic sclerosis
    Souren Paul, Mark H. Kaplan, Dinesh Khanna, Preston M. McCourt, Anjan K. Saha, Pei-Suen Tsou, Mahek Anand, Alexander Radecki, Mohamad Mourad, Amr H. Sawalha,et al.
    Springer Science and Business Media LLC
    AbstractCentromere defects in Systemic Sclerosis (SSc) have remained unexplored despite the fact that many centromere proteins were discovered in patients with SSc. Here we report that lesion skin fibroblasts from SSc patients show marked alterations in centromeric DNA. SSc fibroblasts also show DNA damage, abnormal chromosome segregation, aneuploidy (only in diffuse cutaneous (dcSSc)) and micronuclei (in all types of SSc), some of which lose centromere identity while retaining centromere DNA sequences. Strikingly, we find cytoplasmic “leaking” of centromere proteins in limited cutaneous SSc (lcSSc) fibroblasts. Cytoplasmic centromere proteins co-localize with antigen presenting MHC Class II molecules, which correlate precisely with the presence of anti-centromere antibodies. CENPA expression and micronuclei formation correlate highly with activation of the cGAS-STING/IFN-β pathway as well as markers of reactive oxygen species (ROS) and fibrosis, ultimately suggesting a link between centromere alterations, chromosome instability, SSc autoimmunity, and fibrosis.

  • GSTO1 confers drug resistance in HCT-116 colon cancer cells through an interaction with TNFαIP3/A20
    Souren Paul, Monika Bhardwaj, and Sun Kang
    Spandidos Publications
    The aim of the present study was to decipher the mechanism of glutathione-S-transferase Ω-1 (GSTO1)-induced drug resistance in colon cancer cells. Cisplatin is used widely as a therapeutic drug in cancer, but colon cancer is the most susceptible to acquired drug resistance. Autophagy is recognized as one of the contributors to drug resistance in cancers. Phase II detoxifying enzymes, such as GSTO1, serve important roles in autophagy-apoptosis cross talk. The present study revealed a novel interaction between GSTO1 and TNFα-induced protein 3/zinc-finger protein A20 (TNFαIP3/A20) as a prime target for cisplatin sensitization in drug-resistant cells. GSTO1 and ATP-binding cassette subfamily B member 1 (ABCB1) were both expressed at higher levels in multidrug-resistant (MDR) HCT-116 cells compared with the wild-type (WT) HCT-116 cells, suggesting they may serve vital roles in multidrug resistance. MDR cells showed autophagy induction, which is dependent on calcium signaling-dependent endoplasmic stress. In WT cells, the mitochondria-dependent pathway leads to apoptosis, which was not observed in MDR cells. The MDR conditions were mimicked by transfecting WT cells with the GSTO1-activation CRISPR plasmid, which induced autophagy. Similarly, MDR cells with GSTO1-knockdown (KD) CRISPR/Cas9 transfection showed reduced autophagy with increased apoptosis. These data revealed a potentially important role of GSTO1 in drug resistance. A GSTO1 pull-down assay detected TNFαIP3/A20 as a binding partner in MDR cells. The data suggested that the expression of TNFαIP3/A20 may be dependent on GSTO1 expression in MDR cells. Targeting either GSTO1 or TNFαIP3/A20 by CRISPR/Cas9 sensitized the MDR cells to cisplatin. GSTO1 and TNFαIP3/A20 dual-KD cells were more sensitive to cisplatin compared with single-gene KD cells. These data highlight the importance of the GSTO1-TNFαIP3/A20 interaction during drug resistance.

  • Fumonisin B1 induces poly (ADP-ribose) (PAR) polymer-mediated cell death (parthanatos) in neuroblastoma
    Souren Paul, Rekha Jakhar, Monika Bhardwaj, Anil Kumar Chauhan, and Sun Chul Kang
    Elsevier BV

  • GSK3b-mediated expression of CUG-translated WT1 is critical for tumor progression
    Hisae Yoshitomi, Kun Y. Lee, Ke Yao, Seung Ho Shin, Tianshun Zhang, Qiushi Wang, Souren Paul, Eunmiri Roh, Joohyun Ryu, Hanyong Chen,et al.
    American Association for Cancer Research (AACR)
    Abstract The Wilms' tumor 1 (WT1) gene is well known as a chameleon gene. It plays a role as a tumor suppressor in Wilms' tumor but also acts as an oncogene in other cancers. Previously, our group reported that a canonical AUG starting site for the WT1 protein (augWT1) acts as a tumor suppressor, whereas a CUG starting site for the WT1 protein (cugWT1) functions as an oncogene. In this study, we report an oncogenic role of cugWT1 in the AOM/DSS-induced colon cancer mouse model and in a urethane-induced lung cancer model in mice lacking cugWT1. Development of chemically-induced tumors was significantly depressed in cugWT1-deficient mice. Moreover, glycogen synthase kinase 3β promoted phosphorylation of cugWT1 at S64, resulting in ubiquitination and degradation of the cugWT1 associated with the F-box−/− WD repeat-containing protein 8. Overall, our findings suggest that inhibition of cugWT1 expression provides a potential candidate target for therapy. Significance: These findings demonstrate that CUG-translated WT1 plays an oncogenic role in vivo, and GSK3β-mediated phosphorylation of cugWT1 induces its ubiquitination and degradation in concert with FBXW8.


  • Vitexin induces apoptosis by suppressing autophagy in multidrug resistant colorectal cancer cells
    Monika Bhardwaj, Hee Jun Cho, Souren Paul, Rekha Jakhar, Imran Khan, Seon-Jin Lee, Bo-Yeon Kim, Manigandan Krishnan, Tejinder Pal Khaket, Hee Gu Lee,et al.
    Impact Journals, LLC
    Cancer treatment is limited due to the diverse multidrug resistance acquired by cancer cells and the collateral damage caused to adjacent normal cells by chemotherapy. The flavonoid compound vitexin exhibits anti-oxidative, anti-inflammatory and anti-tumor activity. This study elucidated the antitumor effects of vitexin and its underlying mechanisms in a multi-drug resistant human colon cancer cell line (HCT-116DR), which exhibits higher levels of multidrug-resistant protein 1 (MDR1) expression as compared with its parental cell line (HCT-116). Here, we observed that vitexin suppressed MDR-1 expression and activity in HCT-116DR cells and showed cytotoxic effect in HCT-116DR cells by inhibiting autophagy and inducing apoptosis in a concentration-dependent manner. Additionally, vitexin treatment caused cleavage of caspase-9 and caspase-3, and upregulated the expression of the pro-apoptotic proteins, BID and Bax. Moreover, the expression of autophagy-related proteins, such as ATG5, Beclin-1 and LC3-II, was markedly reduced by vitexin treatment. Furthermore, in vivo experiments showed that vitexin induced apoptosis and suppressed tumor growth in HCT-116DR xenograft model. These results revealed that vitexin induced apoptosis through suppression of autophagy in vitro and in vivo and provide insight into the therapeutic potential of vitexin for the treatment of chemo-resistant colorectal cancer.

  • Thymol elicits HCT-116 colorectal carcinoma cell death through induction of oxidative stress
    Anil Kumar Chauhan, Ashutosh Bahuguna, Souren Paul, and Sun Chul Kang
    Bentham Science Publishers Ltd.
    BACKGROUND Colon cancer is one of the most deadly and common carcinomas occurring worldwide and there have been many attempts to treat this cancer. The present work was designed in order to evaluate thymol as a potent drug against colon cancer. MATERIALS AND METHODS Cytotoxicity of thymol at different concentrations was evaluated against a human colon carcinoma cell line (HCT-116 cells). Fluorescent staining was carried out to evaluate the level of ROS as well as mitochondrial and DNA fragmentation and immunoblot analysis were performed to confirm apoptosis and mitoptosis. RESULTS AND CONCLUSION Results of the study demonstrated that thymol efficiently created an oxidative stress environment inside HCT-116 cells, a colorectal carcinoma cell line, through induction of ROS production along with intense damage to DNA and mitochondria, as observed through Hoechst and rhodamine 123 staining, respectively. Moreover, expression of PARP-1, p-JNK, cytochrome-C and caspase-3 proteins was up-regulated, suggesting HCT-116 cells underwent mitoptotic cell death. Therefore, thymol could be used as a potent drug against colon cancer due to its lower toxicity and prevalence in natural medicinal plants.

  • Vitexin confers HSF-1 mediated autophagic cell death by activating JNK and ApoL1 in colorectal carcinoma cells
    Monika Bhardwaj, Souren Paul, Rekha Jakhar, Imran Khan, Ji In Kang, Ho Min Kim, Jong Won Yun, Seon-Jin Lee, Hee Jun Cho, Hee Gu Lee,et al.
    Impact Journals, LLC
    Heat shock transcription factor-1 (HSF-1) guards the cancerous cells proteome against the alterations in protein homeostasis generated by their hostile tumor microenvironment. Contrasting with the classical induction of heat shock proteins, the pro-oncogenic activities of HSF-1 remains to be explored. Therefore, cancer's fragile proteostatic pathway governed by HSF-1 could be a potential therapeutic target and novel biomarker by natural compounds. Vitexin, a natural flavonoid has been documented as a potent anti-tumor agent on various cell lines. However, in the present study, when human colorectal carcinoma HCT-116 cells were exposed to vitexin, the induction of HSF-1 downstream target proteins, such as heat shock proteins were suppressed. We identified HSF-1 as a potential molecular target of vitexin that interact with DNA-binding domain of HSF-1, which inhibited HSF-1 oligomerization and activation (in silico). Consequently, HSF-1 hyperphosphorylation mediated by JNK operation causes transcriptional inactivation of HSF-1, and supported ROS-mediated autophagy induction. Interestingly, in HSF-1 immunoprecipitated and silenced HCT-116 cells, co-expression of apolipoprotein 1 (ApoL1) and JNK was observed which promoted the caspase independent autophagic cell death accompanied by p62 downregulation and increased LC3-I to LC3-II conversion. Finally, in vivo findings confirmed that vitexin suppressed tumor growth through activation of autophagic cascade in HCT-116 xenograft model. Taken together, our study insights a probable novel association between HSF-1 and ApoL-1 was established in this study, which supports HSF-1 as a potential target of vitexin to improve treatment outcome in colorectal cancer.

  • Novel quercetin derivative TEF induces ER stress and mitochondria-mediated apoptosis in human colon cancer HCT-116 cells
    Imran Khan, Souren Paul, Rekha Jakhar, Monika Bhardwaj, Jaehong Han, and Sun Chul Kang
    Elsevier BV

  • 5-Hydroxy-7-methoxyflavone triggers mitochondrial-associated cell death via reactive oxygen species signaling in human colon carcinoma cells
    Monika Bhardwaj, Na-Hyung Kim, Souren Paul, Rekha Jakhar, Jaehong Han, and Sun Chul Kang
    Public Library of Science (PLoS)
    Plant-derived compounds are an important source of clinically useful anti-cancer agents. Chrysin, a biologically active flavone found in many plants, has limited usage for cancer chemotherapeutics due to its poor oral bioavailability. 5-Hydroxy-7-methoxyflavone (HMF), an active natural chrysin derivative found in various plant sources, is known to modulate several biological activities. However, the mechanism underlying HMF-induced apoptotic cell death in human colorectal carcinoma cells in vitro is still unknown. Herein, HMF was shown to be capable of inducing cytotoxicity in HCT-116 cells and induced cell death in a dose-dependent manner. Treatment of HCT-116 cells with HMF caused DNA damage and triggered mitochondrial membrane perturbation accompanied by Cyt c release, down-regulation of Bcl-2, activation of BID and Bax, and caspase-3-mediated apoptosis. These results show that ROS generation by HMF was the crucial mediator behind ER stress induction, resulting in intracellular Ca2+ release, JNK phosphorylation, and activation of the mitochondrial apoptosis pathway. Furthermore, time course study also reveals that HMF treatment leads to increase in mitochondrial and cytosolic ROS generation and decrease in antioxidant enzymes expression. Temporal upregulation of IRE1-α expression and JNK phosphorylation was noticed after HMF treatment. These results were further confirmed by pre-treatment with the ROS scavenger N-acetyl-l-cysteine (NAC), which completely reversed the effects of HMF treatment by preventing lipid peroxidation, followed by abolishment of JNK phosphorylation and attenuation of apoptogenic marker proteins. These results emphasize that ROS generation by HMF treatment regulates the mitochondrial-mediated apoptotic signaling pathway in HCT-116 cells, demonstrating HMF as a promising pro-oxidant therapeutic candidate for targeting colorectal cancer.

  • Herbacetin is a novel allosteric inhibitor of ornithine decarboxylase with antitumor activity
    Dong Joon Kim, Eunmiri Roh, Mee-Hyun Lee, Naomi Oi, Do Young Lim, Myoung Ok Kim, Yong-Yeon Cho, Angelo Pugliese, Jung-Hyun Shim, Hanyong Chen,et al.
    American Association for Cancer Research (AACR)
    Abstract Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the first step of polyamine biosynthesis that is associated with cell growth and tumor formation. Existing catalytic inhibitors of ODC have lacked efficacy in clinical testing or displayed unacceptable toxicity. In this study, we report the identification of an effective and nontoxic allosteric inhibitor of ODC. Using computer docking simulation and an in vitro ODC enzyme assay, we identified herbacetin, a natural compound found in flax and other plants, as a novel ODC inhibitor. Mechanistic investigations defined aspartate 44 in ODC as critical for binding. Herbacetin exhibited potent anticancer activity in colon cancer cell lines expressing high levels of ODC. Intraperitoneal or oral administration of herbacetin effectively suppressed HCT116 xenograft tumor growth and also reduced the number and size of polyps in a mouse model of APC-driven colon cancer (ApcMin/+). Unlike the well-established ODC inhibitor DFMO, herbacetin treatment was not associated with hearing loss. Taken together, our findings defined the natural product herbacetin as an allosteric inhibitor of ODC with chemopreventive and antitumor activity in preclinical models of colon cancer, prompting its further investigation in clinical trials. Cancer Res; 76(5); 1146–57. ©2015 AACR.




  • Quercetin-3-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside suppresses melanin synthesis by augmenting p38 MAPK and CREB signaling pathways and subsequent cAMP down-regulation in murine melanoma cells
    Hyun Gug Jung, Han Hyuk Kim, Souren Paul, Jae Yoon Jang, Yong Hun Cho, Hyeon Jeong Kim, Jae Myo Yu, Eun Su Lee, Bong Jeun An, Sun Chul Kang,et al.
    Elsevier BV

  • 3,5,7,3′,4′-Pentamethoxyflavone, a quercetin derivative protects DNA from oxidative challenges: Potential mechanism of action
    Rekha Jakhar, Souren Paul, Young Rong Park, Jaehong Han, and Sun Chul Kang
    Elsevier BV

  • Potentiation of macrophage activity by thymol through augmenting phagocytosis
    Anil Kumar Chauhan, Rekha Jakhar, Souren Paul, and Sun Chul Kang
    Elsevier BV

  • Morin hydrate augments phagocytosis mechanism and inhibits LPS induced autophagic signaling in murine macrophage
    Rekha Jakhar, Souren Paul, Anil Kumar Chauhan, and Sun Chul Kang
    Elsevier BV

  • Protective effect of polyamine extract of salt stressed and sprouted soybean seeds against ethanol-induced gastric ulcer in rats
    Kandhasamy Sowndhararajan, Souren Paul, Gi Seok Kwon, Cher Won Hwang, and Sun Chul Kang
    Springer Science and Business Media LLC

  • Natural polyamine inhibits mouse skin inflammation and macrophage activation
    Souren Paul and Sun Chul Kang
    Springer Science and Business Media LLC

  • Elevated antioxidant potential of chlorocholine chloride-treated in vitro grown Stevia rebaudiana Bertoni
    Avishek Dey, Souren Paul, Sayanti Kundu, Abhijit Bandyopadhyay, and Aloke Bhattacharjee
    Springer Science and Business Media LLC

  • Studies on the viability and membrane integrity of human spermatozoa treated with essential oil of Trachyspermum ammi (L.) Sprague ex Turrill fruit
    S. Paul and S. C. Kang
    Wiley
    The present study aimed at investigating the effects of essential oil of Trachyspermum ammi fruits, an oil‐bearing plant of Apiaceae family, on human sperm viability and membrane integrity. Chemical compositions of the oil were analysed by GC‐MS. Thirty compounds representing 91.39% of the total oil were identified. The viability and membrane integrity of human spermatozoa were assessed using minimum effective dose (MED) concentration (125 μg ml−1) of the oil. Sperm treated with essential oil showed a significant decrease (P < 0.05) in viability assessed by eosin–nigrosin and fluorescence dual staining. Moreover, the treated sperm also showed a significant loss (P < 0.05) of functional mitochondria and antioxidant enzyme, catalase (EC 1.11.1.6, CAT), when compared to control. The cholesterol:phospholipid ratio was also increased (P < 0.05) in treated sperm when compared to control, which is an indicator of loss of binding ability of human spermatozoa to the zona pellucida. The scanning electron microscopic studies demonstrated the loss of membrane integrity in essential oil–treated human spermatozoa, which showed vacuolation, swelling of acrosomal cap, detachment of head portion and tail coiling. Present observations indicate the spermicidal property of essential oil of T. ammi fruits, which could be helpful to develop medicinal preparations as a male contraceptive.




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