Dalton's Lymphoma Research Articles

Supramolecular assemblies involving energetically significant unconventional π(CN)-π and anion-π(nitrile) contacts in Zn(II) coordination compounds: Antiproliferative evaluation and theoretical studies

Two new coordination compounds of Zn(II) involving cyanopyridine ligands viz. [Zn(2,6-PDC)(3-CNpy)(H2O)2] (1) and [Zn(4-CNpy)2Cl2] (2) (2,6-PDC = 2,6-pyridinedicarboxylate, 3-CNpy = 3-cyanopyridine, 4-CNpy = 4-cyanopyridine) have been synthesized and characterized using elemental analysis, TGA, spectroscopic (FT-IR, electronic and 1H-NMR) techniques and single crystal XRD. Crystal structure analyses of 1 and 2 unfold the presence of unusual π(CN)-π interactions which provide stability to the layered assemblies of the compounds. Anion-π with parallel nitrile–nitrile interactions in 1 and unconventional anion-π(nitrile) with antiparallel nitrile-nitrile interactions in 2 also contribute to the stability of the crystal structures. Antiparallel CO⋯CO interactions give additional reinforcement to the crystal structure of 1. DFT calculations in combination with MEP surface and NCI plot/QTAIM analyses on different self-assembled supramolecular dimers of the compounds revealed that the unusual CN···π interactions in 1 and Chlorine-π(nitrile) in 2 are energetically significant. The studies also reveal that both H-bonding and π-stacking interactions are energetically important for the stability of the compounds. Compounds 1 and 2 mediated anticancer evaluation on Dalton's lymphoma (DL) cancer cells has been explored considering cytotoxicity and apoptosis assays. The compounds induce significant concentration dependent cytotoxicity in DL cells with negligible effects on normal PBMC cells. Molecular docking studies reveal that the compounds effectively interact with the active sites of antiapoptotic proteins which are actively involved in cancer progression. Pharmacophore features of the structures of the compounds have been finally identified to establish the structure activity relationships (SAR).

Half-sandwich ruthenium(II), rhodium(III) and iridium(III) fluorescent metal complexes containing pyrazoline based ligands: DNA binding, cytotoxicity and antibacterial activities

A series of nine new complexes of ruthenium(II), rhodium(III), and iridium(III) incorporated with pyrazoline-based ligands were synthesized and characterized by various spectroscopic techniques such as FTIR, 1H NMR, 13C NMR, UV-Vis spectroscopy, ESI-MS spectrometry and X-ray crystallographic studies. All the synthesized compounds were assessed for their antibacterial abilities against Gram-positive and Gram-negative bacterial strains. The compounds showed better antibacterial activity against two Gram-positive bacteria (Staphylococcus aureus and Bacillus Thuringiensis), with activities superior to standard kanamycin. Antioxidant studies revealed the mild radical scavenging proficiency of the compounds. DNA binding studies using fluorescence spectroscopy showed that the compounds could bind to Salmon Milt DNA electrostatically via external contact and groove surface binding with moderate affinity. The synthesized complexes were tested for anticancer activity using cell cytotoxicity and apoptosis assays in Dalton's lymphoma (DL) cell lines. The findings were compared to cisplatin (the standard drug) under identical experimental conditions. The cell viability results showed that complex 7 induced higher cytotoxicity in the DL cell line than the other tested compounds. The results of the molecular docking analysis further suggest that selective complexes have complete contact with the active amino acids sites of anti-apoptotic Bcl-2 family protein.

Moringa oleifera L. leaf extract induces cell cycle arrest and mitochondrial apoptosis in Dalton's Lymphoma: An in vitro and in vivo study

Ethnopharmacological relevanceThe present work is based on a wide spectrum of evidences available from scientific literature which reflects nutritional and medicinal values of natural products such as plants and their extracts. Moringa oleifera is one such popular plant species amidst indigenous tribal communities which is frequently used to treat ailments such as piles, sore throat, eye and ear infections and even poisonous bites of tropical fauna such as insects or snakes. Furthermore decoction of leaf and bark was used to cure fever and cough. Evidences further reveal that Moringa oleifera L. (Family Moringaceae), is widely distributed not only over the Indian sub-continent, but also over Philippines, Central America, Saudi Arabia and the Caribbean Islands and have been traditionally used to treat cancers since ancient times. However, therapeutic effects of Moringa oleifera on Non-Hodgkin Lymphoma (NHL) are yet to be established. Aim of the studyThe study aims to investigate the anti-cancer effects of Moringa oleifera leaf extract against murine NHL Non-Hodgkin cells in vitro and in vivo. Material and methodsThe pharmacologically active compounds of Moringa oleifera leaf extract were identified by GC-HRMS analysis. Tests of Moringa oleifera leaf extract's cytotoxicity against DL cells were carried out using the MTT assay. Chromatin condensation along with other morphological alterations were visualized through Fluorescence microscopy. Changes in the mitochondrial membrane potential (ΔΨm), the cell cycle, and apoptosis were analysed through flow cytometer. We tried to identify proteins involved in apoptosis and cell cycle through Western blotting using BALB/c mice as a model organism. ResultsGC-HRMS study revealed that a methanol based leaf extract of Moringa oleifera (MOML) comprises of a variety of bioactive chemicals. Our results indicate that MOML successfully reduced the proliferation of DL cells by lowering ΔΨm, changing overall cell morphology. DL cells treated with MOML showed arrested cell cycle at the G2/M phase and substantially up-regulated the expression of p53 and p21. Elevated levels of Bax, Cyt-c, and Caspase-3 and lowered expression levels of Bcl-2 protein suggested induction of apoptosis. Mechanistically, the anticancer efficacy of MOML is attributed to MEK/ERK-mediated pathway inactivation in DL cells. It is also interesting to note that MOML-mediated inhibition of DL growth was accompanied by apoptosis induction and improvement in hematological parameters in DL-bearing mice. ConclusionOur finding suggested that MOML induces apoptosis and abrogates the growth of Dalton's lymphoma both in vitro and in vivo.

A novel role of Tinospora cordifolia in amelioration of cancer-induced systemic deterioration by taming neutrophil infiltration and hyperactivation

BackgroundCancer has emerged as a systemic disease which targets various organs thus challenging the overall physiology of the host. Recently, we have shown that hyperactive neutrophils infiltrate various organs of tumor bearing host and contribute to gradual systemic deterioration. Therefore, taming neutrophils via potent immunomodulators could be an appropriate therapeutic approach in regulating systemic damage. Tinospora cordifolia (TC), an Ayurvedic panacea, is known for its immense medicinal values in traditional literature and recent reports have also documented its immunomodulatory potential. However, whether TC can regulate neutrophils to exert its therapeutic effectiveness has not been deciphered so far. MethodsFor the in vivo study, we utilized murine model of Dalton's Lymphoma (DL). T. cordifolia extract (TCE) treatment was scheduled at early, mid and advanced stages of tumor growth at a dose of 400 mg/kg b.w for 30 consecutive days. Effect of TCE on neutrophil infiltration was examined by immunostaining. Neutrophil elastase (NE) level in serum, ascitic fluid and various tissues was monitored by ELISA. Further, qPCR was performed to assess transcripts levels of NE, myeloperoxidase (MPO), metalloproteinases (MMP-8, MMP-9) and cathepsin G (CSTG) in various tissues. ROS level in tissue was assessed by DHE staining and organ function was assessed by histology post TCE treatment. ResultsOur findings showed that TC treatment significantly reduced neutrophil count in peripheral blood and their infiltration in vital organs of tumor-bearing host. Further, it ameliorated neutrophil hyperactivation by down regulating the expression of its key cargoes including NE, MPO, MMP-8, MMP-9 and CSTG at early and mid stage of tumor growth. In addition, TC treatment prevented histopathological alterations and restored the normal serum enzyme levels at different stages of tumor growth. Importantly, TC treatment also showed significant reduction in tumor burden which was accompanied by a remarkable increase in survival of the tumor-bearing mice. ConclusionsWe conclude that T. cordifolia could limit systemic damage via regulating neutrophil infiltration and hyperactivation which can further lead to cancer control at both prophylactic and therapeutic level.

Co-expression and Interaction of Pax6 with Genes and Proteins of Immunological Surveillance in the Brain of Mice.

The Pax6 binds to promoter sequence elements of genes involved in immunological surveillance and interacts with Iba1, p53, Ras-GAP, and Sparc in the brain of mice. The Pax6 also affects the expression pattern of genes involved in neurogenesis and neurodegeneration. However, the expression and association of Pax6 in the brain under immunologically challenged conditions are still elusive. Therefore, it has been intended to analyze the association of Pax6 in the immunity of the brain using the immune-challenged Dalton's lymphoma (DL) mice model. The expressions of Pax6, Iba1, and Tmem119 decreased, but expressions of Ifn-γ, Tnf-α, Bdnf, and Tgf-β increased in the brain of immune-challenged mice as compared to the control. The level of co-expression of Pax6 decreased in dual positive cells with Iba1, Tmem119, Sparc, p53, Bdnf, and Tgf-β in the brain of immune-challenged mice. Binding of Pax6 to multiple sites of the promoter sequences of Bdnf and Tgf-β indicates their Pax6-associated differential expression and association with immune responsive gene. The levels of binding of Pax6 to Tmem119, Iba1, Ifn-γ, and Tnf-α got altered during the immune-challenged state as compared to control. Results provide the first evidence of the association of Pax6 in brain-specific immunity.

γc cytokine-aided crosstalk between dendritic cells and natural killer cells together with doxorubicin induces a healer response in experimental lymphoma by downregulating FOXP3 and programmed cell death protein 1

Background aimsThe stimulatory natural killer–dendritic cell axis in the tumor microenvironment could play a critical role in stimulating cytotoxic T cells and driving immune responses against cancer. MethodsWe established a novel treatment protocol by adroitly combining chemotherapy with doxorubicin and immunotherapy with dendritic cells and natural killer cells against a highly aggressive and malignant lymphoma called Dalton's lymphoma. ResultsOur data suggest that binary application of adoptive cell therapy and chemotherapy nearly cures (95%) early-stage experimental lymphoma. In the case of mid-stage cancer, the success rate was significantly lower but still impressive (75%). Our results demonstrated that the application of combination therapy in early-stage cancer significantly reduced the tumor volume and extended the lifespan of the experimental animal in addition to reinvigorating the immune system, including restoring the effector functions of dendritic cells and natural killer cells. The novel protocol limits the metastasis of tumor cells in vascularized organs and rearms the adaptive immune response mediated by dendritic cells and CD4+ and CD8+ T cells. ConclusionsCombination therapy in the early stage alters the cytokine profile, increases interferon-γ and tumor necrosis factor-α in the serum of treated animals and downregulates programmed cell death protein 1 expression in CD8+ T cells. Thus, cooperative and cognitive interactions between dendritic cells and natural killer cells in addition to therapy with doxorubicin promote the immune response and tumoricidal activities against lymphoma.

Supramolecular assemblies involving unconventional non-covalent contacts in pyrazole-based coordination compounds of Co(II) and Cu(II) pyridinedicarboxylates: Antiproliferative evaluation and theoretical studies

Two coordination compounds of Co(II) and Cu(II) viz. [Co(2,6-PDC)(Hdmpz)3]·H2O (1) and [Cu(2,6-PDC)(Hdmpz)2] (2) (2,6-PDC = 2,6-pyridinedicarboxylate, Hdmpz = 3,5-dimethylpyrazole) have been synthesized and characterized using single crystal XRD, elemental analysis, TGA, electronic, FT-IR and 1H NMR spectroscopy. Crystal structure analysis of 1 and 2 reveals the presence of supramolecular assemblies involving various non-covalent interactions. The crystal structure of 1 is stabilized by a structure guiding hydrogen bonded synthon involving the lattice water molecules and unusual double anion–π interactions involving the carboxylate moieties of 2,6-PDC. Unconventional CH⋯π(carbonyl) and CH⋯π(chelate) contacts involving carbonyl moiety and the chelate ring of 2,6-PDC observed in the crystal structure of 2 also provide rigidity to the layered assemblies. Such unconventional CH⋯π contacts involving carbonyl moiety and chelate ring of 2,6-PDC are scarcely explored. DFT calculations in combination with QTAIM and NCI Plot analyses have been performed on supramolecular dimers of the compounds to explore the energetic features of the self-assembled dimers. The large dimerization energies of the dimers indicate the significance of these non-covalent interactions in governing solid state stabilities of the compounds. Antiproliferative evaluation of the compounds considering cell cytotoxicity and apoptosis assays revealed that the compounds induced significant concentration dependent cytotoxicity in Dalton’s lymphoma (DL) cancer cells with nominal effects on normal PBMC cells. Molecular docking and pharmacophore modelling studies of the compounds have been further carried out to establish the structure activity relationship (SAR).

Glutor, a Glucose Transporter Inhibitor, Exerts Antineoplastic Action on Tumor Cells of Thymic Origin: Implication of Modulated Metabolism, Survival, Oxidative Stress, Mitochondrial Membrane Potential, pH Homeostasis, and Chemosensitivity.

Neoplastic cells overexpress glucose transporters (GLUT), particularly GLUT1 and GLUT3, to support altered metabolism. Hence, novel strategies are being explored to effectively inhibit GLUTs for a daunting interference of glucose uptake. Glutor, a piperazine-2-one derivative, is a newly reported pan-GLUT inhibitor with a promising antineoplastic potential. However, several aspects of the underlying mechanisms remain obscure. To understand this better, tumor cells of thymic origin designated as Dalton’s lymphoma (DL) were treated with glutor and analyzed for survival and metabolism regulatory molecular events. Treatment of tumor cells with glutor caused a decrease in cell survival with augmented induction of apoptosis. It also caused a decrease in glucose uptake associated with altered expression of GLUT1 and GLUT3. HIF-1α, HK-2, LDH-A, and MCT1 also decreased with diminished lactate production and deregulated pH homeostasis. Moreover, glutor treatment modulated the expression of cell survival regulatory molecules p53, Hsp70, IL-2 receptor CD25, and C-myc along with mitochondrial membrane depolarization, increased intracellular ROS expression, and altered Bcl-2/BAX ratio. Glutor also enhanced the chemosensitivity of tumor cells to cisplatin, accompanied by decreased MDR1 expression. Adding fructose to the culture medium containing glutor reversed the latter’s inhibitory action on tumor cell survival. These results demonstrate that in addition to inhibited glucose uptake, modulated tumor growth regulatory molecular pathways are also implicated in the manifestation of the antineoplastic action of glutor. Thus, the novel findings of this study will have a long-lasting clinical significance in evaluating and optimizing the use of glutor in anticancer therapeutic strategies.

Terephthalato and succinato bridged Mn(II) and Zn(II) coordination polymers involving structure-guiding H-bonded tetrameric assemblies: Antiproliferative evaluation and theoretical studies

Two new coordination polymers of Mn(II) and Zn(II) viz. {[Mn(µ-tp)(3-Ampy)2(H2O)2]2(3-Ampy)·2(H2O)}n (1) and {[Zn(µ-succ)(3-Ampy)2]·2H2O}n (2) (tp = terephthalate, 3-Ampy = 3-aminopyridine, succ = succinate) have been synthesized and characterized using elemental and spectroscopic analyses, TGA and single crystal X-ray diffraction techniques. Uncoordinated 3-AMpy and water molecules of the polymeric co-crystal hydrate 1 are involved in the formation of cyclic tetrameric {(3-Ampy)2(H2O)2} assembly which provide rigidity to the structure. The presence of guest 3-Ampy and water molecules in the voids of supramolecular Mn(II) host tetramer in 1 provides additional reinforcement to the crystal structure. The lattice water molecules of 2 are aggregated via non-covalent interactions to form discrete cyclic {(H2O)4} tetrameric clusters in the crystal structure. Density functional theory (DFT), non-covalent index (NCI) plot and quantum theory of atoms in molecules (QTAIM) computational analyses reveal that the supramolecular H-bonded cyclic tetrameric structure-guiding synthon in 1 and the (H2O)4 cyclic water clusters in 2 have significant energetic contribution towards the stability of the polymers. In vitro anticancer activities of the compounds considering trypan blue and apoptosis assays revealed that the compounds induce concentration dependent cytotoxicity in Dalton’s lymphoma (DL) cancer cells with nominal effects in normal peripheral blood mononuclear cells (PBMC) cells. Comparative analysis reveals that compound 2 induced higher apoptosis in DL cells; which is well consistent with the trypan blue exclusion assay. Molecular docking and pharmacophore modelling studies of the compounds reveal that the compound 2 significantly interacts with the antiapoptotic proteins to establish structure activity relationship (SAR).

Structural, spectral, cytotoxic and biocatalytic studies of a dinuclear phenoxo bridged Zn(II) complex from NNO donor tridentate Schiff base

• A zinc(II) complex derived from an NNO donor Schiff base system is discussed. • Complex is a centrosymmetric dinuclear phenoxo bridged compound. • Type I halogen interaction present in the crystal system is investigated. • Complex exhibits in vitro cytotoxicity against Dalton's lymphoma ascites cell lines. • Complex shows catecholase like activity in DMF medium. A zinc(II) complex of an NNO donor tridentate Schiff base, 4‑chloro-2-(((3-(methylamino)propyl)imino)methyl)phenol (HL) was synthesised and characterized by different physicochemical methods including single crystal XRD, elemental analysis, IR and electronic spectral analysis. Zinc(II) complex is a centrosymmetric dinuclear phenoxo bridged compound which crystallized in triclinic P 1 ¯ space group. There are a large number of intermolecular hydrogen bonding interactions present in the crystal system which give rise to the formation of a 2D supramolecular assembly and the visual analysis of those intermolecular interactions was done by Hirshfeld surface analysis. Type I halogen interactions, which are quite uncommon, are also discussed based on angular preference, intermolecular distance, and the size of the Cl atom. Complex exhibited negative solvatochromism. Luminescent properties were investigated and quenching of fluorescence was observed which is supported by the quantum yield values. Cytotoxic activity of the complex has been screened in vitro against lymphoma ascites cell lines. In addition, catecholase activity of the complex has been investigated in DMF medium and found that complex was able to catalyze the aerobic oxidation of 3,5-di‑ tert -butylcatechol (3,5-DTBC) to the corresponding quinone.

Effects of Semecarpus anacardium L.f. ethanol extract on serum biochemical parameters and antioxidant activity of DAL induced mice

Semecarpus anacardium L.f. nuts is one of the best, versatile and most commonly used herbs as a household remedy, distributed in sub-Himalayan region, Tropical region, Bihar, Bengal, Orissa and central and south parts of India. In this work, the anticancer efficacy of ethanol extract of Semecarpus anacardium nuts (EESA) was tested in Swiss albino mice with induced Dalton's Ascites Lymphoma (DAL). Ethanol extract of S. anacardium nuts was given daily for 14 days at doses of 200 mg/kg and 400 mg/kg body weight, after 24 hrs of tumor inoculation. After receiving the final dose and fasting for 18 hrs, the mice were euthanized. Serum biochemical and antioxidant characteristics were measured to determine antitumor activity. 5-Fluoro Uracil, a typical medication, was employed as a positive control. In comparison to the control group, ethanol extract-treated mice restored biochemical and antioxidant parameters to near-normal levels. Biochemical and antioxidant parameters in the Dalton's Ascited Lymphoma (DAL) animal model treated with EESA exhibited similar effects as the positive control drug 5-fluorouracil. Overall, the active ingredients present in ethanol extract of Semecarpus anacardium nuts, modulate serum biochemical and antioxidant parameters and bring about anti-tumor activity against Dalton's Ascites Lymphoma (DAL) in mice.

Nickel (II), Copper (II), and Zinc (II) Complexes of N-bis (4-methoxybenzyl) Dithiocarbamate: Synthesis, Characterization Studies, and Evaluation of Antitumor Activity

Three new complexes with the general formula [M(L)2] (L=N-bis(4-methoxybenzyl) dithiocarbamate; M= Ni(II) 1, Cu(II) 2, and Zn(II) 3 ), have been synthesized, and characterized by elemental analysis, IR, UV–visible, 1H, 13C NMR and mass spectrometry. The magnetic behavior of nickel and copper complexes was measured and found to be diamagnetic and paramagnetic, respectively. Complex 3 crystallized in the monoclinic space group P21/c and possessed a centrosymmetric dimeric structure stabilized by weak C-H···S, C-H···π, and C-H…O intermolecular interactions. Electronic absorption spectral studies of the complexes show the absorption band in the range of 270-331 nm, which is due to intraligand charge transfer transitions. Complexes 1 and 2 also show transitions in the range of 325-475 nm due to ligand to metal charge transfer transition. The antitumor activities of the complexes have been screened, and the results obtained show that the metal complexes have significant antitumor activity against Dalton's lymphoma cells in a concentration-dependent manner, and the metal complexes were relatively tolerant to normal human cells with low or marginal toxicity against both lymphocytes and monocytes.

Isolation and characterization of anti-inflammatory and anti-proliferative compound, for B-cell Non-Hodgkin lymphoma, from Nyctanthes arbor-tristis Linn.

Ethnopharmacological relevanceNyctanthes arbor-tristis Linn. is native to Indo-Pak sub-continent and has high medicinal values in Ayureda. This plant has been used traditionally for the treatment of sciatica, rheumatism, chronic fever, diabetes, snakebite, dysentery, cachexia and cancer. Studies have shown many pharmacological properties such as anti-cancer efficacy against Dalton's ascetic lymphoma, cytotoxicity against T-cell leukemia, anti-inflammatory, anti-diabetic and anti-oxidant effects. Aim of the studyAim of the study was to explore the anti-inflammatory and anti-proliferative potential of N. arbor-tristis. Material and methodsEthanol extract of fresh and uncrushed aerial parts of N. arbor-tristis was used in the present study. A new compound nyctanthesin A was isolated following a bioactivity-guided fractionation and chromatographic separations. Its chemical structure was elucidated through spectral studies including 1D, 2D-NMR experiments and HREIMS. The intracellular reactive oxygen species (ROS) and nitric oxide (NO) generation from phagocytes were detected by chemiluminescence technique and Griess method, respectively. TNF-α and TGF-β production was quantified by ELISA. Anti-lymphoma and cytotoxic activities were assessed by alamar blue and MTT assays, respectively. The transcription and protein expression level of Bcl-2, COX-2, p38 MAPK, PDL-1, NF-κB, c-Myc and PNF-κB was performed by qRT-PCR and protein blot assays, respectively. ResultsPetroleum ether insoluble fraction of the ethanol extract of fresh and uncrushed aerial parts of N. arbor-tristis revealed anti-inflammatory potential by inhibiting ROS. A previously undescribed compound nyctanthesin A was isolated from this fraction and characterized by UV, IR, NMR and HREIMS. It showed significant anti-inflammatory property by inhibiting ROS, NO and TNF-α production. The strong anti-proliferative effects on B- cell lymphoma cells, DOHH2 and Raji, revealed its anti-lymphoma potential along with non-toxic profile against BJ and NIH-3T3 fibroblast cells of normal origin. The qRT-PCR results showed marked inhibition of Bcl-2, COX-2, p38 MAPK, PDL-1, c-Myc, NF-κB, and PNF-κB at transcription level in DOHH2 cells with comparatively lesser but significant effects in Raji cells, where the expression of Bcl-2 gene was not affected. The protein expression of PNF-κB in DOHH2 cells was inhibited by 66% (P < 0.05) and COX-2 in both cell lines was inhibited by 50% (P < 0.05) at 60 μg/mL. A moderate non-significant inhibition of TGF-β (∼20%) was observed in both cell lines at 100 μg/mL ConclusionsScientific evidences reported here validate the anti-inflammatory and anti-cancer potential of the plant.

Phytochemical Profiling of Microalgae Euglena tuba and Its Anticancer Activity in Dalton's Lymphoma Cells.

Natural phytochemicals are considered safe to use as therapeutic agents. There is a growing trend toward exploring anticancer effects of crude algal extracts or their active ingredients. Euglena tuba, a microalga, contains excellent antioxidant potential. However, the anticancer property of E. tuba has not been explored. This study investigates the chemical profiling as well as antitumor property of methanolic extract of E. tuba (ETME) against Dalton's lymphoma (DL) cells. E. tuba, procured from northern part of India, was extracted in 70% methanol, dried at room temperature, and stored at -20 ∘C for future use. A freshly prepared aqueous solution of ETME of different concentrations was employed into each experiment. The ETME mediated anti-tumor response in Dalton's lymphoma was evaluated in the inbred populations of BALB/c (H2d) strain of mice of either sex at 8-12 weeks of age. The cytotoxicity of ETME in cancer cells, effects on morphology of cell and nucleus, alteration in the mitochondrial membrane potential, and level of expression of proapoptotic proteins (Bcl-2, cyt C, Bax and p53) were done using known procedures. The ETME contained high content of total alkaloids (96.02 ± 3.30 mg/100 mg), flavonoids (15.77 ± 2.38 mg/100 mg), carbohydrate (12.71 ± 0.59 mg/100 mg), ascorbic acid (12.48 ± 2.59 mg/100 mg), and phenolics (0.94 ± 0.05 mg/100 mg). Gas chromatography-mass spectrometry (GC-MS) analysis indicated the presence of 23 phytochemicals with known anticancer properties. DL cells treated with ETME exhibited significant and concentration dependent cytotoxicity. Florescent microscopy and flow cytometry of ETME treated DL cells indicated significant repair in cellular morphology and decreased mitochondrial potential, respectively. Western blot analysis displayed up-regulation of proapoptotic proteins (Bax, Cyt-c, p53) and down regulation of anti-apoptotic protein (Bcl2) in DL cells treated with ETME. The findings of this study clearly indicated that the anticancer property of ETME was mediated via reduction in mitochondrial potential and induction of apoptotic mechanism. Further studies are warranted to explore the anticancer activities of active ingredients present in this microalga of pharmaceutical importance.

Effect of Substituents on the Photodynamic Action of Anthraquinones: EPR, Computational and In Vitro Studies.

Anthraquinone class of compounds possesses a broad spectrum of therapeutic applications. Cancer cell targeting ability, together with photogeneration of reactive oxygen species, renders anthraquinones an interesting class of photosensitizers for photodynamic therapy (PDT). Screening of newer compounds for better singlet oxygen generation is of current interest to improve the practical usability in PDT. In this study, we investigate the photodynamic activity of nine commercially available anthraquinones, using EPR spectroscopy and computational techniques, to identify the role of substituents on singlet oxygen yield. Three anthraquinone derivatives, 1,5-diaminoanthraquinone, 15-dihydroxyanthraquinone and 1,2,7-trihydroxyanthraquinone, showed highest singlet oxygen quantum yield (0.21, 0.18 and 0.15, respectively) relative to Rose Bengal. Time-dependent density functional theory calculations indicate the singlet oxygen quantum yield of anthraquinones inversely correlate well with the excited singlet-triplet (S1-T1) energy gap. Electron-donating substituents present at positions 1, 2 and 5 of anthraquinone seem to reduce the S1-T1 energy gap, facilitating inter-system crossing and the production of singlet oxygen. This would greatly aid in the design of newer anthraquinone-based photosensitizers. This study also highlights the suitability of 1,5-diaminoanthraquinone for PDT applications as demonstrated by invitro experiments of photoinduced DNA cleavage and photocytotoxicity in Dalton's lymphoma ascites.

Cobalt (III) complex exerts anti-cancer effects on T cell lymphoma through induction of cell cycle arrest and promotion of apoptosis.

Cobalt-based compounds are emerging as a non-platinum-based anti-cancer effective therapeutic agent. However, there is a limited study regarding the therapeutic efficacy of Cobalt-based drugs against Non-Hodgkin's Lymphoma (NHLs) such as T cell lymphoma. Therefore, in the present study we investigated the anti-tumor role of cobalt(III) complex [Co(ptsm)NH3(o-phen)]·CH3OH on Dalton's Lymphoma (DL) cells. Cytotoxicity of the cobalt complex was estimated by MTT assay. Analysis of mitochondrial membrane potential, cell cycle and Reactive oxygen species (ROS) generation, and Annexin V/PI staining was done by Flow cytometry, while AO/EtBr staining by fluorescence microscopy in cobalt complex treated DL cell. Expression of cell cycle and apoptosis regulatory protein was analyzed by Western blotting. In addition, in vivo study of the cobalt complex was evaluated in well-established DL bearing mice by monitoring physiological parameters and mean survival time. Our study showed that cobalt complex triggered apoptosis and induced cell cycle arrest in DL cells. Furthermore, this also decreased mitochondrial membrane potential and increased intracellular ROS generation in cancer cells. In addition, changed expression of cell cycle and apoptosis regulatory protein was found with enhanced activity of caspase-3 and 9 in the treated cells. Additionally, administration of cobalt complex showed a significant increase in the survivability of tumor-bearing host, which was accomplished by decreasing physiological parameters. Taken together, these data revealed anti-tumor potential of cobalt complex against DL cells through cell cycle arrest and mitochondrial-dependent apoptosis. Henceforth, cobalt-based drugs could be a new generation therapeutic drug to treat hematological malignancies.

Pithecellobium dulce induces apoptosis and reduce tumor burden in experimental animals via regulating pro-inflammatory cytokines and anti-apoptotic gene expression

The present study demonstrates the efficacy of fruit extract of Pithecellobium dulce (FPD) against Dalton's lymphoma ascites (DLA) cell lines in vitro and in vivo (DLA induced ascitic and solid tumor). Administration of FPD induced apoptosis in DLA cells via p53 regulation both in vitro and in vivo. Cell viability was quantified by MTT assay. Apoptotic cells were determined by qualitative (staining methods) and quantitative analysis (Annexin-propidium iodide based flow cytometry). Expression of pro-apoptotic markers (Caspase 3, Caspase 9, and Bax) were markedly elevated, while expression of anti-apoptotic proteins (Bcl 2 and Bcl XL) were downregulated in tumor cells. FPD administration effectively reduced tumor burden, increased mean survival time via modulating NF-kB, and reduced the level of proinflammatory cytokines (IL-6, IL-1β, GM-CSF and TNF-α). Phytochemical screening of FPD by GC/MS analysis divulged the presence of several novel bioactive chemical constituents. Further, bioactive components identified from extract were evaluated for drug-like properties by Lipinski rule of five and properties. Naringenin, nootkatone, and gallic acid showed good drug-like properties and good pharmacokinetic profiles compared to other bioactive constituents in the extract.

New triterpenoids and sterol with potent cytotoxic activity from Justicia simplex – Isolation, characterisation and biological evaluation

Justicia is the largest genus of Acanthaceae family with nearly 600 species. Approximately eighteen species were chemically and biologically studied. Attempts were made to isolate, characterize and study the cytotoxic properties of three-petrol ether soluble components namely Methyl-(3β)-3, 23 dihydroxy olean-12-en-28-oate, 3β (Valeryloxy) olean-5,12-dien-1β, 11α, 28β -triol and Stigmasta-5, 20-dien-3β -yl undecanoates were isolated for the first time from this plant. The in vitro antiproliferative potential was assessed against MCF-7 and HeLa cells using MTT assay. 3β (Valeryloxy) olean-5,12-dien-1β, 11α, 28β -triol exhibited cytotoxicity in vitro with an IC50 value of 20.55 and 22.14 µg/mL for HeLa and MCF-7 cell lines respectively, which may be attributed to its apoptotic potential. Apoptotic property of the compounds was confirmed by the Ethidium bromide and Acridine orange double staining methods. 3β (Valeryloxy) olean-5,12-dien-1 β,11 α, 28β -triol revealed better apoptotic activity. Antitumor activity was evaluated by Daltons Lymphoma Ascites induced solid tumour model. Petrol ether extract of Justicia simplex at a dose of 200 mg/kg was capable of producing 71.74% of tumour inhibition. The newly isolated ester derivative of hederagenin and stigmasterol exhibited better cytotoxicity than the earlier reported compounds

Ruthenium, rhodium, and iridium complexes featuring coumarin hydrazone derivatives: Synthesis, characterization, and preliminary investigation of their anticancer and antibacterial activity

Coumarin hydrazone derivatives (L1, L2, L3, and L4) have been prepared by Knoevenagel condensation. Half‐sandwich ruthenium, rhodium, and iridium complexes containing these coumarin hydrazone derivatives (1–12) have been synthesized. The deprotonation of hydrazinic proton from the ligand leads to the formation of anionic species, thereby forming neutral N ∩ N chelation complexes. These complexes have been confirmed by spectroscopic technique and single‐crystal X‐ray diffraction studies. Spectroscopic analysis of the ligands and complexes shows that the data are consistent with the formulated data. The stability studies of some of the complexes (1, 5, and 6) were performed by the 1H‐NMR technique using deuterated DMSO‐d6 solvent. They are found to be stable in solution as well as in the air and are nonhygroscopic. In vitro antibacterial activity against gram‐positive Staphylococcus aureus and gram‐negative Escherichia coli, Klebsiella pneumoniae strains have been tested. Also, their cytotoxicity study was evaluated against Dalton's ascites lymphoma (DL), Ehrlich ascites carcinoma (EAC), and normal cell lines (peripheral blood mononuclear cells [PBMC]). In both the studies, complexes (5 and 6) are found to be the most active compared to the other complexes.

Anti cancer potential of 4H- chromene siprooxindole hybrid molecules against Dalton’s Lymphoma (DL) cells

The anticancer efficacy of 4H- Chromene Spirooxindole hybrid molecules 4i-m1 (Samples 1- 5) was investigated on Dalton’s lymphoma (non-Hodgkin lymphoma) cells. Dalton’s lymphoma (DL) is a spontaneous and highly invasive T-cell lymphoma that develops as an ascitic tumor in murines. It was observed that treatment of DL cells with compounds showed significant decrease in cell viability, altered morphology, nuclear disintegration and DNA fragmentation into low molecular weight DNA fragments and thus characteristic of apoptosis. In this view, these compounds may be used as potential therapeutic regimen to treat this type of cancer in experimental mice.