Skip to main content

SATABDI DATTA

Follower

1

Following

1

Mentions

1

Public Views

Interests

Uploads

Papers by SATABDI DATTA

Bacterioboat—A novel tool to increase the half-life period of the orally administered drug

Science Advances, 2022

The short half-life in the GI tract necessitates an excess of drugs causing side effects of oral ... more The short half-life in the GI tract necessitates an excess of drugs causing side effects of oral formulations. Here, we report the development and deployment of Bacterioboat, which consists of surface-encapsulated mesoporous nanoparticles on metabolically active Lactobacillus reuteri as a drug carrier suitable for oral administration. Bacterioboat showed up to 16% drug loading of its dry weight, intestinal anchorage around alveoli regions, sustained release, and stability in physiological conditions up to 24 hours. In vivo studies showed that oral delivery of 5-fluorouracil leads to increased potency, resulting in improved shrinkage of solid tumors, enhanced life expectancy, and reduced side effects. This novel design and development make this system ideal for orally administrable drugs with low solubility or permeability or both and even making them effective at a lower dose.

NMK-BH2, a novel microtubule-depolymerising bis (indolyl)-hydrazide-hydrazone, induces apoptotic and autophagic cell death in cervical cancer cells by binding to tubulin at colchicine – site

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2020

BACKGROUND Microtubules, the key components of the eukaryotic cytoskeleton and mitotic spindle ar... more BACKGROUND Microtubules, the key components of the eukaryotic cytoskeleton and mitotic spindle are one of the most sought-after targets for cancer chemotherapy, especially due to their indispensible role in mitosis. Cervical cancer is a prevalent malignancy among women of developing countries including India. In spite of the remarkable therapeutic advancement, the non-specificity of chemotherapeutic drugs adversely affects the patients' survival and well-being, thus, necessitating the quest for novel indole-based anti-microtubule agent against cervical cancer, with high degree of potency and selectivity. METHODS For in vitro studies, we used MTT assay, confocal microscopy, fluorescence microscopy, flow cytometry and Western blot analysis. Study in cell free system was accomplished by spectrophotometry, fluorescence spectroscopy and TEM and computational analysis was done by AutodockTools 1.5.6. RESULTS NMK-BH2 exhibited significant and selective anti-proliferative activity against cervical cancer HeLa cells (IC50 = 1.5 μM) over normal cells. It perturbed the cytoskeletal and spindle microtubules of HeLa cells leading to mitotic block and cell death by apoptosis and autophagy. Furthermore, NMK-BH2 targeted the tubulin-microtubule system through fast and strong binding to the αβ-tubulin heterodimers at colchicine-site. CONCLUSION This study identifies and characterises NMK-BH2 as a novel anti-microtubule agent and provides insights into its key anti-cancer mechanism through two different cell death pathways: apoptosis and autophagy, which are mutually independent. GENERAL SIGNIFICANCE It navigates the potential of the novel bis (indolyl)-hydrazide-hydrazone, NMK-BH2, to serve as lead for development of new generation microtubule-disrupting chemotherapeutic with improved efficacy and remarkable selectivity towards better cure of cervical cancer.

Paclitaxel-encapsulated core–shell nanoparticle of cetyl alcohol for active targeted delivery through oral route

Nanomedicine, 2019

Aim: Paclitaxel (PTX) has no clinically available oral formulations. Cetyl alcohol is metabolized... more Aim: Paclitaxel (PTX) has no clinically available oral formulations. Cetyl alcohol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase that are overexpressed in cancer cells. So, PTX-encapsulated core–shell nanoparticle of cetyl alcohol (PaxSLN) could target the cancer cells through oral route. Materials & methods: PaxSLN was synthesized using microemulsion template. Efficiency of PaxSLN was evaluated by ALDEFLUOR™, multicellular tumor spheroid formation inhibition assays and CT26 colorectal carcinoma animal model. Pharmacokinetics and biodistribution studies were done in Sprague Dawley rats. Results: PTX was encapsulated at the core of approximately 78 nm PaxSLN. PaxSLN targeted aldehyde dehydrogenase overexpressing cells. Its oral bioavailability was approximately 95% and chemotherapeutic efficacy was better than Taxol® and nab-PTX. Conclusion: A novel oral nanoformulation of PTX was developed.

Correction to: Autophagy inhibition with chloroquine reverts paclitaxel resistance and attenuates metastatic potential in human nonsmall lung adenocarcinoma A549 cells via ROS mediated modulation of β-catenin pathway

Apoptosis, 2019

Autophagy inhibition with chloroquine reverts paclitaxel resistance and attenuates metastatic potential in human nonsmall lung adenocarcinoma A549 cells via ROS mediated modulation of β-catenin pathway

Apoptosis, 2019

Paclitaxel is one of the most commonly used drugs for the treatment of nonsmall cell lung cancer ... more Paclitaxel is one of the most commonly used drugs for the treatment of nonsmall cell lung cancer (NSCLC). However acquired resistance to paclitaxel, epithelial to mesenchymal transition and cancer stem cell formation are the major obstacles for successful chemotherapy with this drug. Some of the major reasons behind chemoresistance development include increased ability of the cancer cells to survive under stress conditions by autophagy, increased expression of drug efflux pumps, tubulin mutations etc. In this study we found that inhibition of autophagy with chloroquine prevented development of paclitaxel resistance in A549 cells with time and potentiated the effect of paclitaxel by increased accumulation of superoxideproducing damaged mitochondria, with elevated ROS generation, it also increased the apoptotic rate and sub G0/ G1 phase arrest with time in A549 cells treated with paclitaxel and attenuated the metastatic potential and cancer stem cell population of the paclitaxel-resistant cells by ROS mediated modulation of the Wnt/β-catenin signaling pathway, thereby increasing paclitaxel sensitivity. ROS here played a crucial role in modulating Akt activity when autophagy process was hindered by chloroquine, excessive ROS accumulation in the cell inhibited Akt activity. In addition, chloroquine pre-treatment followed by taxol (10 nM) treatment did not show significant toxicity towards non-carcinomas WI38 cells (lung fibroblast cells). Thus autophagy inhibition by CQ pre-treatment can be used as a fruitful strategy to combat the phenomenon of paclitaxel resistance development as well as metastasis in lung cancer.

Novel nano-insulin formulation modulates cytokine secretion and remodeling to accelerate diabetic wound healing

Nanomedicine : nanotechnology, biology, and medicine, Jan 10, 2018

Little is known about insulin's wound healing capability in normal as well as diabetic condit... more Little is known about insulin's wound healing capability in normal as well as diabetic conditions. We here report specific interaction of silver nanoparticles (AgNPs) with insulin by making a ~2 nm thick coat around the AgNPs and its potent wound healing efficacy. Characterization of the interaction of human insulin with silver nanoparticles showed confirmed alteration of amide-I in insulin whereas amide-II and III remained unaltered. Further, nanoparticles protein interaction kinetics showed spontaneous interaction at physiological temperature with ΔG, ΔS, Ea and Ka values -7.48, 0.076, 3.84 kcal mol and 6 × 10 s respectively. Insulin loaded AgNPs (IAgNPs) showed significant improvement in healing activity in vitro (HEKa cells) and in vivo (Wister Rats) in comparison with the control in both normal and diabetic conditions. The underlying mechanism was attributed to a regulation of the balance between pro (IL-6, TNFα) and anti-inflammatory cytokines (IL-10) at the wound site to ...

Development of novel bis(indolyl)-hydrazide-hydrazone derivatives as potent microtubule- targeting cytotoxic agents against A549 lung cancer cells

Biochemistry, May 25, 2016

The biological significance of microtubules makes them a validated target of cancer therapy. In t... more The biological significance of microtubules makes them a validated target of cancer therapy. In this study, we have utilized indole, an important pharmacological scaffold, to synthesise novel bis(indolyl)-hydrazide-hydrazone derivatives (NMK-BH compounds) and recognised NMK-BH3 as the most effective one in inhibiting A549 cell proliferation and assembly of tissue purified tubulin. Cell viability experiments showed that NMK-BH3 inhibited proliferation of human lung adenocarcinoma (A549) cells and normal human lung fibroblast (WI38) and Peripheral Blood Mononuclear Cells (PBMC) with IC50 values of ~2 µM, 48.5 µM and 62 µM , respectively. Thus, relative high cytotoxicity of NMK-BH3 towards lung carcinoma (A549) cells over normal lung fibroblast (WI38) and PBMC cells confers therapeutic advantage of reduced host toxicity. Flow cytometry, Western blot and immunofluorescence studies in A549 cell line revealed that NMK-BH3 induced G2/M arrest, mitochondrial depolarisation and apoptosis by ...

Colchicine induces autophagy and senescence in lung cancer cells at clinically admissible concentration: potential use of colchicine in combination with autophagy inhibitor in cancer therapy

Tumor Biology, 2016

Colchicine is a well-known and potent microtubule targeting agent, but the therapeutic value of c... more Colchicine is a well-known and potent microtubule targeting agent, but the therapeutic value of colchicine against cancer is limited by its toxicity against normal cells. But, there is no report of its cytotoxic potential against lung cancer cell, at clinically permissible or lower concentrations, minimally toxic to non-cancerous cells. Hence, in the present study, we investigated the possible mechanism by which the efficacy of colchicine against lung cancer cells at less toxic dose could be enhanced. Colchicine at clinically admissible concentration of 2.5 nM had no cytotoxic effect and caused no G2/M arrest in A549 cells. However, at this concentration, colchicine strongly hindered the reformation of cold depolymerised interphase and spindle microtubule. Colchicine induced senescence and reactive oxygen species mediated autophagy in A549 cells at this concentration. Autophagy inhibitor 3-methyladenine (3-MA) sensitised the cytotoxicity of colchicine in A549 cells by switching senescence to apoptotic death, and this combination had reduced cytotoxicity to normal lung fibroblast cells (WI38). Together, these findings indicated the possible use of colchicine at clinically relevant dose along with autophagy inhibitor in cancer therapy.

Inhibition of autophagy by chloroquine potentiates synergistically anti-cancer property of artemisinin by promoting ROS dependent apoptosis

Biochimie, 2014

Inhibition of autophagy by chloroquine potentiates synergistically anti-cancer property of artemi... more

Covid-19 pandemic in India: Chronological comparison of the regional heterogeneity in the pandemic progression and gaps in mitigation strategies

COVID-19 second wave, in India, exerted more catastrophe than the first. The progressions of both... more COVID-19 second wave, in India, exerted more catastrophe than the first. The progressions of both waves were heterogeneous in the six different regions involving 28 states and 8 union territories. An analysis of the temporal variations in new cases and fatalities in all the states of India was done for both the 1st (30th January 2020 to 31st January 2021) and 2nd wave (1st February 2021 to 29th May 2021) showed India accounted for over 16% and 9% of the cases and fatalities of the world respectively. The Southern and Western regions remained the top contributor of cases and fatalities in both waves. The state of Punjab and Maharashtra reported the highest CFR (3.24 and 2.5 respectively) in the country during 1st wave, and in the second wave, Andaman & Nicobar Islands (2.6), and Punjab (2.25) reported the highest CFR. Goa and Delhi showed the highest CCR and CDR for 1st wave respectively, whereas Lakshadweep and Goa reported the highest CCR and CDR respectively in the 2nd wave. The s...

Paclitaxel resistance development is associated with biphasic changes in reactive oxygen species, mitochondrial membrane potential and autophagy with elevated energy production capacity in lung cancer cells: A chronological study

Tumor Biology, 2017

Paclitaxel (Tx) is one of the first-line chemotherapeutic drugs used against lung cancer, but acq... more Paclitaxel (Tx) is one of the first-line chemotherapeutic drugs used against lung cancer, but acquired resistance to this drug is a major challenge against successful chemotherapy. In this work, we have focused on the chronological changes of various cellular parameters and associated effect on Tx (10 nM) resistance development in A549 cell line. It was observed, at initial stage, the cell death percentage due to drug treatment had increased up to 20 days, and thereafter, it started declining and became completely resistant by 40 days. Expressions of βIII tubulin and drug efflux pumps also increased over the period of resistance development. Changes in cellular autophagy and reactive oxygen species generation showed a biphasic pattern and increased gradually over the course of upto 20 days, thereafter declined gradually; however, their levels remained higher than untreated cells when resistance was acquired. Increase in extracellular acidification rates and oxygen consumption rates ...

Bacterioboat—A novel tool to increase the half-life period of the orally administered drug

Science Advances, 2022

The short half-life in the GI tract necessitates an excess of drugs causing side effects of oral ... more The short half-life in the GI tract necessitates an excess of drugs causing side effects of oral formulations. Here, we report the development and deployment of Bacterioboat, which consists of surface-encapsulated mesoporous nanoparticles on metabolically active Lactobacillus reuteri as a drug carrier suitable for oral administration. Bacterioboat showed up to 16% drug loading of its dry weight, intestinal anchorage around alveoli regions, sustained release, and stability in physiological conditions up to 24 hours. In vivo studies showed that oral delivery of 5-fluorouracil leads to increased potency, resulting in improved shrinkage of solid tumors, enhanced life expectancy, and reduced side effects. This novel design and development make this system ideal for orally administrable drugs with low solubility or permeability or both and even making them effective at a lower dose.

NMK-BH2, a novel microtubule-depolymerising bis (indolyl)-hydrazide-hydrazone, induces apoptotic and autophagic cell death in cervical cancer cells by binding to tubulin at colchicine – site

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2020

BACKGROUND Microtubules, the key components of the eukaryotic cytoskeleton and mitotic spindle ar... more BACKGROUND Microtubules, the key components of the eukaryotic cytoskeleton and mitotic spindle are one of the most sought-after targets for cancer chemotherapy, especially due to their indispensible role in mitosis. Cervical cancer is a prevalent malignancy among women of developing countries including India. In spite of the remarkable therapeutic advancement, the non-specificity of chemotherapeutic drugs adversely affects the patients' survival and well-being, thus, necessitating the quest for novel indole-based anti-microtubule agent against cervical cancer, with high degree of potency and selectivity. METHODS For in vitro studies, we used MTT assay, confocal microscopy, fluorescence microscopy, flow cytometry and Western blot analysis. Study in cell free system was accomplished by spectrophotometry, fluorescence spectroscopy and TEM and computational analysis was done by AutodockTools 1.5.6. RESULTS NMK-BH2 exhibited significant and selective anti-proliferative activity against cervical cancer HeLa cells (IC50 = 1.5 μM) over normal cells. It perturbed the cytoskeletal and spindle microtubules of HeLa cells leading to mitotic block and cell death by apoptosis and autophagy. Furthermore, NMK-BH2 targeted the tubulin-microtubule system through fast and strong binding to the αβ-tubulin heterodimers at colchicine-site. CONCLUSION This study identifies and characterises NMK-BH2 as a novel anti-microtubule agent and provides insights into its key anti-cancer mechanism through two different cell death pathways: apoptosis and autophagy, which are mutually independent. GENERAL SIGNIFICANCE It navigates the potential of the novel bis (indolyl)-hydrazide-hydrazone, NMK-BH2, to serve as lead for development of new generation microtubule-disrupting chemotherapeutic with improved efficacy and remarkable selectivity towards better cure of cervical cancer.

Paclitaxel-encapsulated core–shell nanoparticle of cetyl alcohol for active targeted delivery through oral route

Nanomedicine, 2019

Aim: Paclitaxel (PTX) has no clinically available oral formulations. Cetyl alcohol is metabolized... more Aim: Paclitaxel (PTX) has no clinically available oral formulations. Cetyl alcohol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase that are overexpressed in cancer cells. So, PTX-encapsulated core–shell nanoparticle of cetyl alcohol (PaxSLN) could target the cancer cells through oral route. Materials & methods: PaxSLN was synthesized using microemulsion template. Efficiency of PaxSLN was evaluated by ALDEFLUOR™, multicellular tumor spheroid formation inhibition assays and CT26 colorectal carcinoma animal model. Pharmacokinetics and biodistribution studies were done in Sprague Dawley rats. Results: PTX was encapsulated at the core of approximately 78 nm PaxSLN. PaxSLN targeted aldehyde dehydrogenase overexpressing cells. Its oral bioavailability was approximately 95% and chemotherapeutic efficacy was better than Taxol® and nab-PTX. Conclusion: A novel oral nanoformulation of PTX was developed.

Correction to: Autophagy inhibition with chloroquine reverts paclitaxel resistance and attenuates metastatic potential in human nonsmall lung adenocarcinoma A549 cells via ROS mediated modulation of β-catenin pathway

Apoptosis, 2019

Autophagy inhibition with chloroquine reverts paclitaxel resistance and attenuates metastatic potential in human nonsmall lung adenocarcinoma A549 cells via ROS mediated modulation of β-catenin pathway

Apoptosis, 2019

Paclitaxel is one of the most commonly used drugs for the treatment of nonsmall cell lung cancer ... more Paclitaxel is one of the most commonly used drugs for the treatment of nonsmall cell lung cancer (NSCLC). However acquired resistance to paclitaxel, epithelial to mesenchymal transition and cancer stem cell formation are the major obstacles for successful chemotherapy with this drug. Some of the major reasons behind chemoresistance development include increased ability of the cancer cells to survive under stress conditions by autophagy, increased expression of drug efflux pumps, tubulin mutations etc. In this study we found that inhibition of autophagy with chloroquine prevented development of paclitaxel resistance in A549 cells with time and potentiated the effect of paclitaxel by increased accumulation of superoxideproducing damaged mitochondria, with elevated ROS generation, it also increased the apoptotic rate and sub G0/ G1 phase arrest with time in A549 cells treated with paclitaxel and attenuated the metastatic potential and cancer stem cell population of the paclitaxel-resistant cells by ROS mediated modulation of the Wnt/β-catenin signaling pathway, thereby increasing paclitaxel sensitivity. ROS here played a crucial role in modulating Akt activity when autophagy process was hindered by chloroquine, excessive ROS accumulation in the cell inhibited Akt activity. In addition, chloroquine pre-treatment followed by taxol (10 nM) treatment did not show significant toxicity towards non-carcinomas WI38 cells (lung fibroblast cells). Thus autophagy inhibition by CQ pre-treatment can be used as a fruitful strategy to combat the phenomenon of paclitaxel resistance development as well as metastasis in lung cancer.

Novel nano-insulin formulation modulates cytokine secretion and remodeling to accelerate diabetic wound healing

Nanomedicine : nanotechnology, biology, and medicine, Jan 10, 2018

Little is known about insulin's wound healing capability in normal as well as diabetic condit... more Little is known about insulin's wound healing capability in normal as well as diabetic conditions. We here report specific interaction of silver nanoparticles (AgNPs) with insulin by making a ~2 nm thick coat around the AgNPs and its potent wound healing efficacy. Characterization of the interaction of human insulin with silver nanoparticles showed confirmed alteration of amide-I in insulin whereas amide-II and III remained unaltered. Further, nanoparticles protein interaction kinetics showed spontaneous interaction at physiological temperature with ΔG, ΔS, Ea and Ka values -7.48, 0.076, 3.84 kcal mol and 6 × 10 s respectively. Insulin loaded AgNPs (IAgNPs) showed significant improvement in healing activity in vitro (HEKa cells) and in vivo (Wister Rats) in comparison with the control in both normal and diabetic conditions. The underlying mechanism was attributed to a regulation of the balance between pro (IL-6, TNFα) and anti-inflammatory cytokines (IL-10) at the wound site to ...

Development of novel bis(indolyl)-hydrazide-hydrazone derivatives as potent microtubule- targeting cytotoxic agents against A549 lung cancer cells

Biochemistry, May 25, 2016

The biological significance of microtubules makes them a validated target of cancer therapy. In t... more The biological significance of microtubules makes them a validated target of cancer therapy. In this study, we have utilized indole, an important pharmacological scaffold, to synthesise novel bis(indolyl)-hydrazide-hydrazone derivatives (NMK-BH compounds) and recognised NMK-BH3 as the most effective one in inhibiting A549 cell proliferation and assembly of tissue purified tubulin. Cell viability experiments showed that NMK-BH3 inhibited proliferation of human lung adenocarcinoma (A549) cells and normal human lung fibroblast (WI38) and Peripheral Blood Mononuclear Cells (PBMC) with IC50 values of ~2 µM, 48.5 µM and 62 µM , respectively. Thus, relative high cytotoxicity of NMK-BH3 towards lung carcinoma (A549) cells over normal lung fibroblast (WI38) and PBMC cells confers therapeutic advantage of reduced host toxicity. Flow cytometry, Western blot and immunofluorescence studies in A549 cell line revealed that NMK-BH3 induced G2/M arrest, mitochondrial depolarisation and apoptosis by ...

Colchicine induces autophagy and senescence in lung cancer cells at clinically admissible concentration: potential use of colchicine in combination with autophagy inhibitor in cancer therapy

Tumor Biology, 2016

Colchicine is a well-known and potent microtubule targeting agent, but the therapeutic value of c... more Colchicine is a well-known and potent microtubule targeting agent, but the therapeutic value of colchicine against cancer is limited by its toxicity against normal cells. But, there is no report of its cytotoxic potential against lung cancer cell, at clinically permissible or lower concentrations, minimally toxic to non-cancerous cells. Hence, in the present study, we investigated the possible mechanism by which the efficacy of colchicine against lung cancer cells at less toxic dose could be enhanced. Colchicine at clinically admissible concentration of 2.5 nM had no cytotoxic effect and caused no G2/M arrest in A549 cells. However, at this concentration, colchicine strongly hindered the reformation of cold depolymerised interphase and spindle microtubule. Colchicine induced senescence and reactive oxygen species mediated autophagy in A549 cells at this concentration. Autophagy inhibitor 3-methyladenine (3-MA) sensitised the cytotoxicity of colchicine in A549 cells by switching senescence to apoptotic death, and this combination had reduced cytotoxicity to normal lung fibroblast cells (WI38). Together, these findings indicated the possible use of colchicine at clinically relevant dose along with autophagy inhibitor in cancer therapy.

Inhibition of autophagy by chloroquine potentiates synergistically anti-cancer property of artemisinin by promoting ROS dependent apoptosis

Biochimie, 2014

Inhibition of autophagy by chloroquine potentiates synergistically anti-cancer property of artemi... more

Covid-19 pandemic in India: Chronological comparison of the regional heterogeneity in the pandemic progression and gaps in mitigation strategies

COVID-19 second wave, in India, exerted more catastrophe than the first. The progressions of both... more COVID-19 second wave, in India, exerted more catastrophe than the first. The progressions of both waves were heterogeneous in the six different regions involving 28 states and 8 union territories. An analysis of the temporal variations in new cases and fatalities in all the states of India was done for both the 1st (30th January 2020 to 31st January 2021) and 2nd wave (1st February 2021 to 29th May 2021) showed India accounted for over 16% and 9% of the cases and fatalities of the world respectively. The Southern and Western regions remained the top contributor of cases and fatalities in both waves. The state of Punjab and Maharashtra reported the highest CFR (3.24 and 2.5 respectively) in the country during 1st wave, and in the second wave, Andaman & Nicobar Islands (2.6), and Punjab (2.25) reported the highest CFR. Goa and Delhi showed the highest CCR and CDR for 1st wave respectively, whereas Lakshadweep and Goa reported the highest CCR and CDR respectively in the 2nd wave. The s...

Paclitaxel resistance development is associated with biphasic changes in reactive oxygen species, mitochondrial membrane potential and autophagy with elevated energy production capacity in lung cancer cells: A chronological study

Tumor Biology, 2017

Paclitaxel (Tx) is one of the first-line chemotherapeutic drugs used against lung cancer, but acq... more Paclitaxel (Tx) is one of the first-line chemotherapeutic drugs used against lung cancer, but acquired resistance to this drug is a major challenge against successful chemotherapy. In this work, we have focused on the chronological changes of various cellular parameters and associated effect on Tx (10 nM) resistance development in A549 cell line. It was observed, at initial stage, the cell death percentage due to drug treatment had increased up to 20 days, and thereafter, it started declining and became completely resistant by 40 days. Expressions of βIII tubulin and drug efflux pumps also increased over the period of resistance development. Changes in cellular autophagy and reactive oxygen species generation showed a biphasic pattern and increased gradually over the course of upto 20 days, thereafter declined gradually; however, their levels remained higher than untreated cells when resistance was acquired. Increase in extracellular acidification rates and oxygen consumption rates ...