Antitumor and Immunostimulatory Activity of Two Chromones and Other Constituents from Cassia Petersiana

Phytochemical and biological investigation of the leaves of Cassia petersiana afforded two new chromones (1, 2), in addition, to the known glyceryl-1-hexacosanoate (3) and stigmasterol-3-O-β-D-glucoside (4). The structures of the compounds were determined by comprehensive NMR studies, including DEPT, COSY, HMQC, HMBC and IR spectroscopy and MS. 1–4 were investigated against different types of cell lines, including solid tumor cells (Hep-G2, and MCF-7 cells) and leukemia (1301) cells for their cytotoxic effects. 1–3 possessed a dose-dependent cytotoxic effect against Hep-G2 cells, but in relatively high concentrations; 4 was the most cytotoxic with the lowest IC50 value of 82.7 μM. The calculated IC50 values against MCF-7 cells were 112.2 μM, 143.7 μM, 68.1 μM, and 114.3 μM for 1, 2, 3, and 4, respectively. The alteration in the macrophage proliferation index, using Raw 264.7 cells, was monitored. 1 and 3 were the highest stimulators of macrophage proliferation in a dose-dependent manner, whereas 2 and 4 showed a peak point of stimulation at 20 μM. The effect of these compounds on pre-induced NO was explored. 1–4 inhibited the LPS-induced NO, with inhibition percentages of 80.5%, 89.3%, 82.1%, and 92.1%, respectively, at a concentration of 20 μM. The antioxidant capacity of 1–4, using the DPPH assay was also investigated. 1–3 possessed weak scavenging activity; while 4 had an effective SC50 value as low as 36 μM. These results indicated that 4 possessed the highest anti-tumor, immunoproliferative, macrophage proliferation, anti-inflammatory, and antioxidant activities.

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Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽

10.3390/pharmaceutics13030386 ◽

2021 ◽

Vol 13 (3) ◽

pp. 386

Author(s):

Tung-Hu Tsai ◽

Yu-Jen Chen ◽

Li-Ying Wang ◽

Chen-Hsi Hsieh

Keyword(s):

Stereotactic Body Radiation Therapy ◽

In Vivo Studies ◽

Control Group ◽

High Dose ◽

Dependent Manner ◽

Hep G2 ◽

Time Curve ◽

Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

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Abstract 619: Alpha Keto Acids Decompose Peroxides and Prevents Oxidation of Lipoproteins

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.619 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Chandrakala Aluganti Narasimhulu ◽

Kathryn Young Burge ◽

Yu Yuan ◽

Sampath Parthasarathy

Keyword(s):

Therapeutic Potential ◽

Lipid Peroxides ◽

Enzymatic Oxidation ◽

Raw 264.7 Cells ◽

Dependent Manner ◽

Gene Expressions ◽

Dual Effect ◽

Keto Acids ◽

Hydroperoxyoctadecadienoic Acid ◽

Dose Dependent

Background: Alpha keto acids are unstable and decompose rapidly. In this study, we tested the ability of alpha keto acids to reduce peroxides and inhibit oxidation of lipoproteins. Methods: Keto salicylic acid (KSA) and Keto Octanoicacid (KoA) were synthesized and their ability to reduce hydrogen peroxides as well as lipid peroxides (LOOH) was measured using 13-hydroperoxyoctadecadienoic acid (13-HPODE). Lipoproteins (LDL and HDL) were isolated from human plasma and oxidation of liporproteins was performed using copper and MPO in the presence or absence of the keto compounds. RAW 264.7 cells and HUVECS were incubated with LPS and mm-LDL respectively either in the presence or absence of the keto compounds. RNA was isolated from treated cells and real time PCR was performed to analyze IL-1α, IL-6, MCP-1 and VCAM1 gene expressions. Reactive oxygen species were evaluated using DCF fluorescence in presence and absence of the keto compounds. Results: KSA reduced both H2O2 and 13-HPODE whereas KoA is able to reduce the former but not the latter. Both compounds inhibited the lipoprotein oxidation in a dose dependent manner and were able to reduce ROS production by H2O2. KSA is able to inhibit both LPS as well as mm-LDL induced inflammation. However, KoA showed a dual effect as it induced inflammatory markers in the presence of LPS, but inhibited the mm-LDL-induced inflammatory gene expressions. Conclusion: The results of our studies suggest that these keto compounds a) inhibit both enzymatic and non enzymatic oxidation of lipoproteins; b) reduce peroxides and ROS and c) have inhibitory and inducing effect on inflammatory cytokine/gene production in presence of mm-LDL and LPS respectively. Based on these results, we predict that these keto compounds could have therapeutic potential in reducing CVD/atherosclerosis-associated inflammation.

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Synthesis and In Vitro Antitumor Activity of Novel Bivalent β-Carboline-3-carboxylic Acid Derivatives with DNA as a Potential Target

International Journal of Molecular Sciences ◽

10.3390/ijms19103179 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3179 ◽

Cited By ~ 4

Author(s):

Hongling Gu ◽

Na Li ◽

Jiangkun Dai ◽

Yaxi Xi ◽

Shijun Wang ◽

...

Keyword(s):

Antitumor Activity ◽

Cell Apoptosis ◽

Docking Studies ◽

In Vitro Cytotoxicity ◽

Dependent Manner ◽

Cycle Arrest ◽

Dna Binding Affinity ◽

Dose Dependent ◽

Mcf 7

A series of novel bivalent β-carboline derivatives were designed and synthesized, and in vitro cytotoxicity, cell apoptosis, and DNA-binding affinity were evaluated. The cytotoxic results demonstrated that most bivalent β-carboline derivatives exhibited stronger cytotoxicity than the corresponding monomer against the five selected tumor cell lines (A549, SGC-7901, Hela, SMMC-7721, and MCF-7), indicating that the dimerization at the C3 position could enhance the antitumor activity of β-carbolines. Among the derivatives tested, 4B, 6i, 4D, and 6u displayed considerable cytotoxicity against A549 cell line. Furthermore, 4B, 6i, 4D, and 6u induced cell apoptosis in a dose-dependent manner, and caused cell cycle arrest at the S and G2/M phases. Moreover, the levels of cytochrome C in mitochondria, and the expressions of bcl-2 protein, decreased after treatment with β-carbolines, which indicated that 6i and 6u could induce mitochondria-mediated apoptosis. In addition, the results of UV-visible spectral, thermal denaturation, and molecular docking studies revealed that 4B, 6i, 4D, and 6u could bind to DNA mainly by intercalation.

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Inhibition of angiotensinogen production by angiotensin II analogues in human hepatoma cell line

AJP Cell Physiology ◽

10.1152/ajpcell.1989.257.5.c888 ◽

1989 ◽

Vol 257 (5) ◽

pp. C888-C895 ◽

Cited By ~ 3

Author(s):

E. Coezy ◽

I. Darby ◽

J. Mizrahi ◽

B. Cantau ◽

M. H. Donnadieu ◽

...

Keyword(s):

Angiotensin Ii ◽

Cell Line ◽

Binding Sites ◽

Inhibitory Effect ◽

Hepatoma Cell Line ◽

Dependent Manner ◽

Human Hepatoma ◽

Ang Ii ◽

Hep G2 ◽

Dose Dependent

The aim of this study was to examine in Hep G2, a human hepatoma-derived cell line, the presence of angiotensin II (ANG II) receptors and the effect of ANG II and its analogues on angiotensinogen production. The presence of ANG II receptors was demonstrated using a long-acting ANG II analogue, 125I-labeled [Sar1]ANG II. A single class of specific binding sites was identified in these cells with a dissociation constant (Kd) of 2 nM. The number and affinity of these binding sites were not changed by [Sar1]ANG II treatment over 24 h. ANG II showed an inhibitory effect on angiotensinogen production. [Sar1]ANG II also exhibited a similar inhibitory effect as that of ANG II but to a greater extent and therefore was used throughout these studies. [Sar1]ANG II inhibited angiotensinogen production in a dose-dependent manner, exhibiting a half-maximal inhibitory concentration (IC50) of 2 nM. Other ANG II analogues showed similar effects on angiotensinogen production. In order of decreasing ability, they were [Sar1]ANG II greater than [Sar1-Ala8]ANG II greater than [Sar1-Val8]ANG II greater than [Sar1-Val5-(Br5)-Phe8]ANG II greater than [Sar1-Val5-DPhe8]ANG II. Results of these studies show that the Hep G2 cell possesses specific ANG II receptors and that [Sar1]ANG II induces a dose-dependent inhibition of angiotensinogen production in this system.

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Physicochemical Properties of Collagen from Acaudina Molpadioides and Its Protective Effects against H2O2-Induced Injury in RAW264.7 Cells

Marine Drugs ◽

10.3390/md18070370 ◽

2020 ◽

Vol 18 (7) ◽

pp. 370

Author(s):

Jie Li ◽

Yan Li ◽

Yuyao Li ◽

Zuisu Yang ◽

Huoxi Jin

Keyword(s):

Sulfonic Acid ◽

Antioxidant Activities ◽

Physicochemical Characterization ◽

Raw264.7 Cells ◽

Composition Analysis ◽

Dependent Manner ◽

Protective Effects ◽

Dose Dependent ◽

Zeta Potential Analysis ◽

Improve Cell Viability

Collagen is a promising biomaterial used in the beauty and biomedical industries. In this study, the physicochemical characterization, antioxidant activities, and protective effects against H2O2-induced injury of collagen isolated from Acaudina molpadioides were investigated. The amino acid composition analysis showed that the collagen was rich in glycine (Gly), alanine (Ala), and glutamic acid (Glu), but poor in tyrosine (Tyr) and phenylalanine (Phe). Zeta potential analysis revealed that the isoelectric point (pI) of collagen from Acaudina molpadioides was about 4.25. It possessed moderate scavenging activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals in a dose-dependent manner. In addition, the collagen was able to effectively improve cell viability and morphology, inhibit the production of Malondialdehyde (MDA), and increase the activities of Superoxide Dismutase (SOD) and Glutathione Peroxidase (GSH-Px) in cultured RAW264.7 cells, resulting in a protective effect against H2O2-induced injury. Overall, the results showed that collagen extracted from A. molpadioides has promising prospects in the beauty and cosmetics industries.

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On the Molecular Pharmacology of Resveratrol on Oxidative Burst Inhibition in Professional Phagocytes

Oxidative Medicine and Cellular Longevity ◽

10.1155/2014/706269 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Radomír Nosáľ ◽

Katarína Drábiková ◽

Viera Jančinová ◽

Tomáš Perečko ◽

Gabriela Ambrožová ◽

...

Keyword(s):

Oxidative Burst ◽

Antioxidant Activities ◽

Raw 264.7 Cells ◽

Human Neutrophils ◽

Nitrite Production ◽

Inos Protein Expression ◽

Dependent Inhibition ◽

Dose Dependent Inhibition ◽

Dose Dependent

Resveratrol—3,5,4′-trihydroxystilbene—possesses antioxidant activitiesin vitro. It dose-dependently inhibited the generation of peroxyl, hydroxyl, peroxides, and lipid peroxidation products in cell free systems. Oxidative burst of whole human blood stimulated with PMA, fMLP, OpZ, and A23187 was inhibited in a concentration-dependent way, indicating suppression of both receptor and nonreceptor activated chemiluminescence by resveratrol. Results from isolated human neutrophils revealed that resveratrol was active extracellularly as well as intracellularly in inhibiting the generation of reactive oxygen species. Liberation of ATP and analysis of apoptosis showed that in the concentration of 100 μM, resveratrol did not change the viability and integrity of isolated neutrophils. Western blot analysis documented that resveratrol in concentrations of 10 and 100 μM significantly decreased PMA-induced phosphorylation of PKCα/βII. Dose-dependent inhibition of nitrite production and iNOS protein expression in RAW 264.7 cells indicated possible interference of resveratrol with reactive nitrogen radical generation in professional phagocytes. The results suggest that resveratrol represents an effective naturally occurring substance with potent pharmacological effect on oxidative burst of human neutrophils and nitric oxide production by macrophages. It should be further investigated for its pharmacological activity against oxidative stress in ischaemia reperfusion, inflammation, and other pathological conditions, particularly neoplasia.

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Therapeutic Effects of Matrine on Primary and Metastatic Breast Cancer

The American Journal of Chinese Medicine ◽

10.1142/s0192415x10008512 ◽

2010 ◽

Vol 38 (06) ◽

pp. 1115-1130 ◽

Cited By ~ 40

Author(s):

Hali Li ◽

Gang Tan ◽

Xian Jiang ◽

Haiquan Qiao ◽

Shangha Pan ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Cells ◽

Metastatic Breast ◽

Proliferation Index ◽

Therapeutic Effects ◽

Dependent Manner ◽

Therapeutic Benefits ◽

4T1 Breast Cancer ◽

Dose Dependent

Matrine, one of the main components extracted from a traditional Chinese herb, Sophora flavescens Ait, has displayed anti-cancer activity in several types of cancer cells. This study aims to evaluate the therapeutic benefits of matrine on primary and metastatic breast cancer. Matrine inhibited the viability of and induced apoptosis in human MCF-7 and mouse 4T1 breast cancer cells in a dose-dependent manner in vitro as shown by MTT assay, flow cytometry and laser scanning confocal microscopy. Administration of matrine inhibited the growth of primary tumors and their metastases to lungs and livers, in a dose-dependent manner, in a highly metastatic model of 4T1 breast cancer established in syngeneic Balb/c mice. Tumors from matrine-treated mice had a smaller proliferation index, shown by immunostaining with an anti-Ki-67 antibody, a greater apoptosis index, shown by TUNEL-staining, and a less microvessel density, shown by immunostaining with an anti-CD31 A antibody, compared to the controls. Western blot analysis of tumoral homogenates indicated that matrine therapy reduced the ratio of Bcl-2/Bax, downregulated the expressions of VEGF and VEGFR-2, and increased the activation of caspase-3 and caspase-9. This study suggests matrine may be a potent agent, from a natural resource, for treating metastatic breast cancer because of its anti-apoptotic, anti-proliferative and anti-angiogenic activities.

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CYTOTOXIC AND ANTIOXIDANT ACTIVITIES OF SECONDARY METABOLITES FROM PULICARIA UNDULATA

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i9.12814 ◽

2016 ◽

Vol 8 (9) ◽

pp. 150 ◽

Cited By ~ 6

Author(s):

Taha A. Hussien ◽

Sayed A. El-toumy ◽

Hossam M. Hassan ◽

Mona H. Hetta

Keyword(s):

Antioxidant Activity ◽

Secondary Metabolites ◽

Antioxidant Activities ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Hep G2 ◽

Structure Activity ◽

Dpph Method ◽

Mcf 7

Objective: To evaluate the in vitro cytotoxicity, antioxidant activities and structure-activity relationship of secondary metabolites isolated from Pulicaria undulata.Methods: The methylene chloride-methanol (1:1) extract of the air-dried aerial parts of Pulicaria undulata was fractionated and separated to obtain the isolated compounds by different chromatographic techniques. Structures of the isolated compounds were determined on the basis of the extensive spectroscopic analysis, including 1D and 2D NMR and compared with the literature data. The crude extract and the isolated compounds were evaluated for in vitro antioxidant activity using the 2,2 diphenyl dipicryl hydrazine (DPPH) method and cytotoxic assay using human breast cancer (MCF-7) and hepatoma (Hep G2) cell line.Results: Nine secondary metabolites were isolated from Pulicaria undulata in this study. Of which two terpenoidal compounds; 8-epi-ivalbin and 11β, 13-dihydro-4H-xanthalongin 4-O-β-D-glucopyranoside firstly isolated from the genus pulicaria and three flavonoids; eupatolitin, 6-methoxykaempferol, and patulitrin firstly isolated from P. undulata. 6-methoxykaempferol (IC50 2.3 µg/ml) showed the most potent antioxidant activity. The highest cytotoxic effect against MCF-7 and Hep G2 cells was obtained with eupatolitin (IC50 27.6 and 23.5 µg/ml) respectively. The structure-activity relationship was also examined and the findings presented here showed that 3, 5, 7, 4' and 3, 5, 4', 5'-hydroxy flavonoids were potent antioxidant and has cytotoxic activity.Conclusion: Pulicaria undulata is a promising medicinal plant, and our study tends to support the therapeutic value of this plant as antioxidant drug and in the treatment of cancer.

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Extract of Rhus verniciflua Stokes Induces p53-Mediated Apoptosis in MCF-7 Breast Cancer Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/9407340 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Min Sung Kim ◽

Chul Won Lee ◽

Jung-Hoon Kim ◽

Jang-Cheon Lee ◽

Won Gun An

Keyword(s):

Breast Cancer ◽

High Performance ◽

Annexin V ◽

Food Supplement ◽

Dependent Manner ◽

Related Factors ◽

Rhus Verniciflua Stokes ◽

Rhus Verniciflua ◽

Dose Dependent ◽

Mcf 7

Rhus verniciflua Stokes has long been used as a food supplement and traditional herbal medicine for various ailments in East Asia. We evaluated the anticancer effects of Rhus verniciflua Stokes extract (RVSE) on MCF-7 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, annexin V/7-AAD staining, and western blotting. In addition, the gallic acid content of RVSE was assayed using high-performance liquid chromatography. RVSE inhibited the growth of MCF-7 cells in a dose-dependent manner by inducing apoptosis in the sub-G1 phase. RVSE also significantly increased the number of apoptotic cells and increased the expression of p53 and p21 in a dose-dependent manner. Furthermore, RVSE treatment increased the Bax:Bcl-2 ratio and the levels of apoptosis-related factors, such as cleaved caspase-3 and -9 and PARP, in MCF-7 cells. Our findings suggest that the proapoptotic effect of RVSE on MCF-7 cells is mediated by p53, p21, and the intrinsic mitochondrial cascade. Thus, RVSE shows promise for the prevention and treatment of breast cancer.

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Bersavine: A Novel Bisbenzylisoquinoline Alkaloid with Cytotoxic, Antiproliferative and Apoptosis-Inducing Effects on Human Leukemic Cells

Molecules ◽

10.3390/molecules25040964 ◽

2020 ◽

Vol 25 (4) ◽

pp. 964 ◽

Cited By ~ 2

Author(s):

Darja Koutova ◽

Monika Kulhava ◽

Radim Havelek ◽

Martina Majorosova ◽

Karel Královec ◽

...

Keyword(s):

Leukemic Cells ◽

Dependent Manner ◽

Carcinoma Cell Lines ◽

Ic50 Values ◽

Bisbenzylisoquinoline Alkaloid ◽

Human Leukemic Cells ◽

Induced Apoptosis ◽

Dose Dependent ◽

Increased Activity ◽

Mcf 7

Bersavine is the new bisbenzylisoquinoline alkaloid isolated from the Berberis vulgaris L. (Berberidaceae) plant. The results of cytotoxicity screening 48 h post-treatment showed that bersavine considerably inhibits the proliferation and viability of leukemic (Jurkat, MOLT-4), colon (HT-29), cervix (HeLa) and breast (MCF-7) cancer cells with IC50 values ranging from 8.1 to 11 µM. The viability and proliferation of leukemic Jurkat and MOLT-4 cells were decreased after bersavine treatment in a time- and dose-dependent manner. Bersavine manifested concentration-dependent antiproliferative activity in human lung, breast, ovarian and hepatocellular carcinoma cell lines using a xCELLigence assay. Significantly higher percentages of MOLT-4 cells exposed to bersavine at 20 µM for 24 h were arrested in the G1 phase of the cell cycle using the flow cytometry method. The higher percentage of apoptotic cells was measured after 24 h of bersavine treatment. The upregulation of p53 phosphorylated on Ser392 was detected during the progression of MOLT-4 cell apoptosis. Mechanistically, bersavine-induced apoptosis is an effect of increased activity of caspases, while reduced proliferation seems dependent on increased Chk1 Ser345 phosphorylation and decreased Rb Ser807/811 phosphorylation in human leukemic cells.

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