Treatment of Ovarian Cancer Cells with Nutlin-3 and Resveratrol Combination Leads to Apoptosis via Caspase Activation

Palanisamy Marimuthu,Kamal Kaur,Umadevi Kandalam,Vandana Jasani,Nidha Bukhari,Michelle Nguyen,Alleesa Abdul,Farheen F. Pervez,Appu Rathinavelu 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.1

The current study was focused on the induction of apoptotic effects of resveratrol along with the combination treatments of nutlin-3 and transforming growth factor-β (TGF-β) against the human ovarian cancer cell line A2780/CP70. To determine the extent of apoptosis following the above-mentioned treatments, we assessed the execution of apoptotic events that proceed via caspase activation and cytochrome c release. We estimated the caspase-3 and -9 activities using a direct enzymatic assay that measures the cleavage of synthetic peptide substrate (N-acetyl-Asp-Glu-Val-Asp-p-nitroanilide). Our experiments showed an increase in caspase-3 and -9 activities in the cells that were treated with the combination of resveratrol (5μM) with nutlin-3 (5μM) or TGF-β (1μg/mL). Since activation of procaspase-3 by caspase-9 requires the release of cytochrome c into the cytoplasm, we measured the levels of cytochrome c in the cytoplasm by western blot experiments. The data indicated a considerable increase in caspase-3 and cytochrome c levels when cells were treated with drugs for 24 hours. Experiments with 4,6′-diamino-2-phenylindole dihydrochloride (DAPI) staining also confirmed the induction of apoptosis in all the above-mentioned treatments done at 24 and 48 hours. These results support our hypothesis that resveratrol combination can induce programmed cell death at doses that

Antibacterial efficacy of a fucoidan fraction (Fu-F2) extracted from <i>Sargassum polycystum</i>

Palanisamy, Subramanian,Vinosha, Manoharan,Rajasekar, Periyannan,Anjali, Ravichandran,Sathiyaraj, Ganesan,Marudhupandi, Thangapandi,Selvam, Samayanan,Prabhu, Narayanasamy Marimuthu,You, SangGuan Elsevier 2019 INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Vol.125 No.-

<P><B>Abstract</B></P> <P>In this study therapeutic potential of fucoidan fraction-2 (Fu-F2) isolated from <I>Sargassum polycystum</I> was evaluated for the development of antibacterial agent against the human and animal pathogenic bacteria by <I>in vitro</I> and <I>in vivo</I> analysis. The Fu-F2 contained 51.12 ± 0.86% of total sugar and 20.41 ± 0.91% of sulfate. The structural characterization of Fu-F2 was performed by HPLC, FTIR and NMR analysis and reported in our earlier study. The <I>in vitro</I> antibacterial assays such as MIC, MBC, killing kinetics, disk diffusion, protein leakage, ROS and confocal laser scanning microscopy demonstrate that Fu-F2 possesses the highest antibacterial activity against the tested pathogens. Among the tested pathogens, the highest antibacterial activity (21 ± 1.0 mm) was recorded at the concentration of 50 μg/ml against <I>Pseudomonas aeruginosa</I> and the lowest activity (16 ± 0.53 mm) was registered against <I>Staphylococcus aureus.</I> In the <I>in vivo</I> analysis, the pre-treatment group with Fu-F2 at the concentration of 15 mg/0.1 kg through feed exhibited the highest survival (83.4%) and antioxidant activities (<I>p</I> < 0.05) than the fish infected with pathogen. Thus, the present findings suggest that the Fu-F2 of <I>S. polycystum</I> encompasses significant antibacterial properties and that can be used as a therapeutic agent for controlling the bacterial disease.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The fucoidan fraction-2 (Fu-F2) was successfully isolated from <I>Sargassum polycystum</I>. </LI> <LI> The antibacterial activity of Fu-F2 was tested by various <I>in vitro</I> and <I>in vivo</I> assays. </LI> <LI> The Fu-F2 shows higher antibacterial activity against <I>P. aeruginosa</I> than the other bacteria. </LI> <LI> The <I>in vivo</I> studies confirmed that Fu-F2 treated zebrafish shows excellent antioxidant properties and improved the histological architecture. </LI> </UL> </P>

Synthesis of <i>Oldenlandia umbellata</i> stabilized silver nanoparticles and their antioxidant effect, antibacterial activity, and bio-compatibility using human lung fibroblast cell line WI-38

Subramanian, Palanisamy,Ravichandran, Anjali,Manoharan, Vinosha,Muthukaruppan, Reka,Somasundaram, Selvakumar,Pandi, Boomi,Krishnan, Anand,Marimuthu, Prabhu Narayanasamy,Somasundaram, Selliah Swamy Nat Elsevier 2019 Process biochemistry Vol.86 No.-

<P><B>Abstract</B></P> <P>In the past few years, green synthesized silver nanoparticles (AgNPs) are one of predominantly used materials in therapeutics and clinical practices. In this study, AgNPs were synthesized from aqueous extract of <I>Oldenlandia umbellata</I> and investigated their pharmaceutical properties. UV–vis spectroscopy of <I>O. umbellata</I> mediated silver nanoparticles (AgNPs@OUa) showed a peak at 423 nm. Fourier transform infrared spectroscopy and phytochemical screening explained the contribution of biomolecules in AgNPs@OUa synthesis. Field emission scanning electron microscope and high-resolution transmission electron microscope examination revealed that small monodispersed spherical nanoparticles had an average size of 22.7 nm. Antioxidant assays were used to examine antioxidant properties of AgNPs@OUa in comparison with <SMALL>L-</SMALL>ascorbic acid (Vitamin C) as a standard antioxidant. AgNPs@OUa showed dose-dependent antioxidant activities. Antibacterial activities of AgNPs@OUa exhibited the highest zone of inhibition against <I>Streptococcus mutans</I> and <I>Escherichia coli</I> were 16.03 ± 0.35 mm and 19.76 ± 0.25 mm, respectively, at concentration of 1.0 mg L<SUP>−1</SUP>. Biocompatibility of AgNPs@OUa against human lung fibroblast (WI-38) cell line was also tested. Even though, the cells treated with the uppermost concentration (100 μg/mL) of AgNPs@OUa, it enhances the cell viability (∼90%), suggesting that AgNPs@OUa had no toxicity with excellent biocompatibility.</P> <P><B>Highlights</B></P> <P> <UL> <LI> First report on the bio synthesis of AgNPs using <I>O. umbellata</I> aqueous extract. </LI> <LI> The AgNPs@OUa were characterized by spectral and microscopy analysis. </LI> <LI> AgNPs@OUa were act as a significant antioxidant and antibacterial activities. </LI> <LI> AgNPs@OUa showed excellent biocompatibility against WI-38 cell lines. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Biogenic synthesis of gold nanoparticles from <i>Halymenia dilatata</i> for pharmaceutical applications: Antioxidant, anti-cancer and antibacterial activities

Vinosha, Manoharan,Palanisamy, Subramanian,Muthukrishnan, Ramasamy,Selvam, Samayanan,Kannapiran, Ethiraj,You, SangGuan,Prabhu, Narayanasamy Marimuthu Elsevier 2019 PROCESS BIOCHEMISTRY Vol.85 No.-

<P><B>Abstract</B></P> <P>Biogenic synthesis of metal nanoparticles using seaweeds is more biocompatible and more valuable for biomedical applications. In this study, gold nanoparticles were synthesized from the aqueous extract of <I>Halymenia dilatata</I> (Hd-AuNPs) and characterized by various spectral and microscopic techniques. The Hd-AuNPs exhibit a surface plasmon resonance peak at 529 nm. FT-IR results confirm the presence of polysaccharides and pigments in the extract, which reduce Au<SUP>3+</SUP> to Au<SUP>0</SUP>. Microscopic analysis confirmed that Hd-AuNPs were triangular and spherical in shape with an average size of 16 nm. In terms of potential antioxidant properties, DPPH radical scavenging (13.7 ± 0.40 to 58.7 ± 0.85%), reducing power (16.3 ± 0.63 to 62.4 ± 0.60%) and total antioxidant (12.4 ± 0.50 to 56.6 ± 0.74%) activities were reasonably high in Hd-AuNPs compared with the extract alone. In the cytotoxicity assay, the IC<SUB>50</SUB> of Hd-AuNPs was 22.62 μg/ml against HT-29 cancer cells. Similarly, in the antibacterial assay, the highest zone of inhibition (21 mm) was recorded at 100 μg/ml against <I>Aeromonas hydrophila</I> and the activity was proportionate to the concentration of Hd-AuNPs. In addition, the biosynthesis of Hd-AuNPs was non-toxic to zebrafish embryo. Overall, synthesized Hd-AuNPs exhibit commendable antioxidant, anti-cancer and antibacterial activities.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Biogenic synthesis of gold nanoparticles using the aqueous extract of <I>H.dilatata</I> </LI> <LI> The synthesized Hd-AuNPs were confirmed by spectral and microscopic examination. </LI> <LI> Antioxidant, Anti-cancer and Antibacterial properties of Hd-AuNPs were studied. </LI> <LI> First report on the biological activities of GNPs synthesized from <I>H. dilatata</I>. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Induction of Apoptosis in HeLa Cells via Caspase Activation by Resveratrol and Genistein

Sivanesan Dhandayuthapani,Palanisamy Marimuthu,Vanessa Hormann,James Kumi-Diaka,Appu Rathinavelu 한국식품영양과학회 2013 Journal of medicinal food Vol.16 No.2

Selectively inducing apoptosis in cancer cells is a much desired strategy when tolerance toward side effects is minimal during chemotherapy. In our search for natural products that can induce apoptosis in human cervical cancer cells (HeLa), we selected resveratrol and genistein for our study. We conducted several experiments to test whether genistein can synergistically enhance the apoptotic potential of resveratrol at doses lower than the usual cytotoxic dose. Both resveratrol and genistein were able to induce apoptosis by enhancing the activities of caspase-9 and caspase-3 by themselves and also in combination. After 24 h of exposure to resveratrol and genistein, individually or in combination, lowered mitochondrial membrane potential was observed in HeLa cells. In addition, the mitochondrial membrane potential in HeLa cells was decreased, forcing JC-1 to stay in the monomeric form. The monomeric JC-1(5,5′,6,6′ -tetrachloro-1,1′,3,3′-tetraethyl benzimedazolyl carbocyanine iodide) emitted green fluorescence. In the control group, the color of the fluorescence was red due to aggregation of JC-1 in the physiological pH. The treatment groups exhibited DNA fragmentation as the hallmark of apoptotic nuclear features. We also detected an obvious decrease in the level of HDM2 gene expression after both individual and combination treatments with resveratrol and genistein. Our findings suggest that resveratrol and genistein when combined can induce apoptosis at doses lower than usual doses, through the activation of caspases cascade, and by decreasing the expression of HDM2.