Dr Soumosish Paul
@apccollege.ac.in
Assistant Professor, Dept. of Zoology
Acharya prafulla chandra college new barrakpore, kolkata West Bengal
RESEARCH INTERESTS
Molecular Biology, Cancer Biology, Cell Biology, Cell Signaling , Immunology
Scopus Publications
Scopus Publications
Soumosish Paul and Gobinda Chandra Sadhukhan
International Journal of Experimental Research and Review
Investigation of the efficacy of the combined drugs chelerythrine and DADS in restoring chemically induced hepatocellular carcinoma in Swiss albino mice. 4-6 week-old mice were considered for experimentation. The genotoxic carcinogen para-induced liver cancer--dimethyl-amino azobenzene along with nongenotoxic promoter carcinogen phenobarbital exposure. During the study, animals were co-treated with 100mg/kg body weight DADS and 5mg/kg body weight chelerythrine individually or in combination for 120 days. Bioparametric enzymatic assays of ALT, AST, ALKP, and GGT were performed. The estimation of TBARS, analysis of bone marrow chromosomal abnormalities, sperm head anomalies, and histopathological tissue structure in the co-treated group followed studies. An increase in enzymatic activities of plasma ALT, AST, ALKP, and GGT was observed after carcinogen exposure. Individual treatment of chelerythrine and DADS restored the activities mentioned above to some extent, although combined drugs successfully maintained the enzymatic activities in plasma. Changes in bone marrow chromosomal morphology and sperm head anomalies after carcinogen exposure were prevented in the individual and, most significantly, after combined drug therapy. Histopathological analysis of liver tissue of both male and female mice also demonstrated the preservation of tissue structures in the treated group, most significantly in the combined treatment, even after PB+P-DAB exposure. Chelerythrine and DADS individually protected liver tissue to a certain extent from the tumorigenic toxic effect of PB+P-DAB exposure. The combination of DADS and chelerythrine successfully guarded the tissue from any corrosive, carcinogenic impact and thus instigated further consideration as an effective alternative therapy against chemically induced hepatocarcinoma.
Dipanwita Sengupta, Kaustav Dutta Chowdhury, Sujan Chatterjee, Avik Sarkar, Soumosish Paul, Pradip Kumar Sur, and Gobinda Chandra Sadhukhan
Springer Science and Business Media LLC
Cancer cells often have faulty apoptotic pathways resulting in sustenance of survivability, tumour metastasis and resistance to anticancer drugs. Alternate strategies are sought to improve therapeutic efficacy and therefore HepG2 cells were treated with S-allyl-cysteine (SAC) and berberine (BER) to analyze their mechanistic impact upon necroptosis along with its interacting relationship to apoptosis. In the present study we observed that SAC and BER exposure reduced NFκβ nuclear translocation through adenylate cyclase-cAMP-protein kinaseA axis and eventually evaded c-FLIP inhibition. Effective RIP1 k63-polyubiquitination and persistent MKK3/MKK6 expression during drug treatment potentiated caspase8 activity via p53—DISC conformation. Resultant tBid associated lysosomal protease mediated AIF truncation induced DNA fragmentation and persuaded effector caspase mediated scramblase activation resulting induction of necroptosis in parallel to apoptotic events. SAC+BER effectively reduced Rb-phosphorylation resulting insignificant nuclear E2F presence led to ending of cell proliferation. Therefore necroptosis augmented the drug response and may be targeted alongside cell proliferation inhibition in formation of efficient therapeutics against liver cancer.
Dipanwita Sengupta, Sujan Chatterjee, Tania Chatterjee, Kaustav Dutta Chowdhury, Priya Bhowmick, Udipta Chakraborti, Avik Sarkar, Soumosish Paul, Pradip Kumar Sur, and Gobinda Chandra Sadhukhan
Springer Science and Business Media LLC
Oxidative stress is proposed to play a pivotal role in the development of hepatocellular carcinoma. With an accelerated metabolism cancer cells demand high reactive species accumulation to maintain their indiscriminate cell growth and proliferation. Here we wanted to see the status of reactive species in the chemically induced liver cancer. For this purpose swiss albino mice were exposed to DEN and CCl4 to develop an in vivo model of hepatocarcinoma. Depletion of cellular antioxidants regulated accretion of reactive species during the development of DEN + CCl4 induced tumor formation in hepatocytes. Currently available therapeutics for heptatocellular carcinoma is costly and coupled with certain bystander effects to the surrounding control cells. Therefore considering the antioxidant properties of SAC and berberine we treated DEN + CCl4 exposed mice after the development of liver tumor. Results effectively pointed out the usefulness of the alternative treatment with SAC and berberine in hepatoprotection. Replenishment of both enzymatic and non enzymatic antioxidant efficiently reduced accumulation of reactive species and that eventually closely associated with effective reduction in tumor number and size after drug treatment in DEN + CCl4 exposed mice.
Dipanwita Sengupta, Kaustav Dutta Chowdhury, Avik Sarkar, Soumosish Paul, and Gobinda Chandra Sadhukhan
Elsevier BV
BACKGROUND
Diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) have been used as initiator and promoter respectively to establish an animal model for investigating molecular events appear to be involved in development of liver cancer. Use of herbal medicine in therapeutics to avoid the recurrence of hepatocarcinoma has already generated considerable interest among oncologists. In this context studies involving S-allyl-cysteine (SAC) and berberine have come up with promising results. Here we have determined the individual effect of SAC and berberine on the biomolecules associated with DEN+CCl4 induced hepatocarcinoma. Effective therapeutic value of combined treatment has also been estimated.
METHODS
ROS accumulation was analyzed by FACS following DCFDA incubation. Bcl2-Bax and HDAC1-pMdm2 interaction were demonstrated by co-immunoprecipitation. Immunosorbent assay was performed to analyze PP2A and caspase3 activities. MMP was determined cytofluorimetrically by investigating JC-1 fluorescence. AnnexinV binding was demonstrated by labeling the cells with AnV-FITC followed by flow cytometry.
RESULTS
CytochromeP4502E1 mediated bioactivation of DEN+CCl4 induced Akt dependent pMdm2-HDAC1 interaction that led to p53 deacetylation, probable cause of its degradation. In parallel, oxidative stress dependent Nrf2-HO1 activation increased Bcl2 expression which in turn stimulated cell proliferation. SAC in combination with berberine inhibited Akt mediated cell proliferation. Activation of PP2A as well as inhibition of JNK resulted in induction of apoptosis after 30 days of treatment. Extension of combined treatment reverted tissue physiology towards control. Co-treated group displayed normal tissue structure.
CONCLUSION AND GENERAL SIGNIFICANCE
SAC and berberine mediated HDAC1/Akt inhibition implicates the efficacy of combined treatment in the amelioration of DEN+CCl4 induced hepatocarcinoma.
Samir Mandal, Sudip Mukherjee, Kaustav Dutta Chowdhury, Avik Sarkar, Kankana Basu, Soumosish Paul, Debasish Karmakar, Mahasweta Chatterjee, Tuli Biswas, Gobinda Chandra Sadhukhan,et al.
Elsevier BV
Corrigendum to “S-allyl cysteine in combination with clotrimazole downregulates Fas induced apoptotic events in erythrocytes of mice exposed to lead” [Biochim. Biophys. Acta 1820 (2012) 9–23] Samir Mandal, Sudip Mukherjee, Kaustav Dutta Chowdhury, Avik Sarkar, Kankana Basu, Soumosish Paul, Debasish Karmakar, Mahasweta Chatterjee, Tuli Biswas, Gobinda Chandra Sadhukhan, Gargi Sen⁎ a Indian Institute of Chemical Biology (CSIR), 4, Raja S.C. Mullick Road, Kolkata-700032, India b Department of Zoology, Vidyasagar College, 39 Sankar Ghosh Lane, Kolkata-700006, India
Samir Mandal, Sudip Mukherjee, Kaustav Dutta Chowdhury, Avik Sarkar, Kankana Basu, Soumosish Paul, Debasish Karmakar, Mahasweta Chatterjee, Tuli Biswas, Gobinda Chandra Sadhukhan,et al.
Elsevier BV
BACKGROUND
Chronic lead (Pb(2+)) exposure leads to the reduced lifespan of erythrocytes. Oxidative stress and K(+) loss accelerate Fas translocation into lipid raft microdomains inducing Fas mediated death signaling in these erythrocytes. Pathophysiological-based therapeutic strategies to combat against erythrocyte death were evaluated using garlic-derived organosulfur compounds like diallyl disulfide (DADS), S allyl cysteine (SAC) and imidazole based Gardos channel inhibitor clotrimazole (CLT).
METHODS
Morphological alterations in erythrocytes were evaluated using scanning electron microscopy. Events associated with erythrocyte death were evaluated using radio labeled probes, flow cytometry and activity gel assay. Mass spectrometry was used for detection of GSH-4-hydroxy-trans-2-nonenal (HNE) adducts. Fas redistribution into the lipid rafts was studied using immunoblotting technique and confocal microscopy.
RESULTS
Combination of SAC and CLT was better than DADS and CLT combination and monotherapy with these agents in prolonging the survival of erythrocytes during chronic Pb(2+) exposure. Combination therapy with SAC and CLT prevented redistribution of Fas into the lipid rafts of the plasma membrane and downregulated Fas-dependent death events in erythrocytes of mice exposed to Pb(2+).
CONCLUSION AND GENERAL SIGNIFICANCE
Ceramide generation was a critical component of Fas receptor-induced apoptosis, since inhibition of acid sphingomyelinase (aSMase) interfered with Fas-induced apoptosis during Pb(2+) exposure. Combination therapy with SAC and CLT downregulated apoptotic events in erythrocytes by antagonizing oxidative stress and Gardos channel that led to suppression of ceramide-initiated Fas aggregation in lipid rafts. Hence, combination therapy with SAC and CLT may be a potential therapeutic option for enhancing the lifespan of erythrocytes during Pb(2+) toxicity.