scholarly journals New Humulenes from Hyptis incana (Labiatae)

2013 ◽  
Vol 8 (12) ◽  
pp. 1934578X1300801
Author(s):  
Mitsuru Satoh ◽  
Yoshio Satoh ◽  
Yasuhiro Anzai ◽  
Daisuke Ajisawa ◽  
Keiichi Matsuzaki ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Inhibitory Activity ◽  
Leukemia Cells ◽  
Moderate Activity ◽  
Mouse Leukemia ◽  
Aerial Parts ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Potent Growth

Two new humulene-type sesquiterpenes, named hyptishumulene I (1) and II (2), have been isolated, together with eight known compounds, a humulene-type sesquiterpene (3), a monoterpene (4) and six abietane-type diterpenoids (5–10) from the aerial parts of Hyptis incana (Labiatae). The cytotoxic activity of the isolated compounds against mouse leukemia cells (L1210) was examined. The abietane-type diterpenoids (5–10) showed rather potent growth inhibitory activity (IC50<15 μM), while the new humulene-type compounds (1 and 2) exhibited moderate activity (IC50>50 μM).

KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation

Blood ◽  
2009 ◽  
Vol 114 (8) ◽  
pp. 1607-1617 ◽  
Author(s):  
Yukimasa Shiotsu ◽  
Hitoshi Kiyoi ◽  
Yuichi Ishikawa ◽  
Ryohei Tanizaki ◽  
Makiko Shimizu ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Leukemia Cells ◽  
Significant Activity ◽  
Wild Type ◽  
Down Regulation ◽  
Multikinase Inhibitor ◽  
Growth Inhibitory ◽  
Imatinib Resistant ◽  
Flt3 Mutations ◽  
Potent Growth

Abstract KW-2449, a multikinase inhibitor of FLT3, ABL, ABL-T315I, and Aurora kinase, is under investigation to treat leukemia patients. In this study, we examined its possible modes of action for antileukemic effects on FLT3-activated, FLT3 wild-type, or imatinib-resistant leukemia cells. KW-2449 showed the potent growth inhibitory effects on leukemia cells with FLT3 mutations by inhibition of the FLT3 kinase, resulting in the down-regulation of phosphorylated-FLT3/STAT5, G1 arrest, and apoptosis. Oral administration of KW-2449 showed dose-dependent and significant tumor growth inhibition in FLT3-mutated xenograft model with minimum bone marrow suppression. In FLT3 wild-type human leukemia, it induced the reduction of phosphorylated histone H3, G2/M arrest, and apoptosis. In imatinib-resistant leukemia, KW-2449 contributed to release of the resistance by the simultaneous down-regulation of BCR/ABL and Aurora kinases. Furthermore, the antiproliferative activity of KW-2449 was confirmed in primary samples from AML and imatinib-resistant patients. The inhibitory activity of KW-2449 is not affected by the presence of human plasma protein, such as α1-acid glycoprotein. These results indicate KW-2449 has potent growth inhibitory activity against various types of leukemia by several mechanisms of action. Our studies indicate KW-2449 has significant activity and warrants clinical study in leukemia patients with FLT3 mutations as well as imatinib-resistant mutations.

A New Triterpenoid Alkaloid from Buxus sempervirens

2011 ◽  
Vol 66 (10) ◽  
pp. 1076-1078 ◽  
Author(s):  
Yu-Xin Yan ◽  
Yun Sun ◽  
Jian-Chao Chen ◽  
Jia Su ◽  
Yan Li ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Spectral Data ◽  
Human Cell ◽  
Spectral Methods ◽  
Inhibitory Activity ◽  
Human Cell Lines ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Buxus Sempervirens ◽  
Mcf 7

A new triterpenoid alkaloid, 16-deacetoxy-hyrcamine (1), together with six analogs, was isolated from the leaves and stems of Buxus sempervirens. Their structures were elucidated based on spectral methods and by comparison of the spectral data with those reported previously. All isolated compounds were evaluated for their growth inhibitory activity against human cell lines HL-60, SMMC-7721, A-549,MCF-7, and SW480. Compounds 1 - 4 and 6 showed modest cytotoxic activity against A-549, MCF-7, and SW480.

scholarly journals Modifications on the Tetrahydroquinoline Scaffold Targeting a Phenylalanine Cluster on GPER as Antiproliferative Compounds against Renal, Liver and Pancreatic Cancer Cells

2021 ◽  
Vol 14 (1) ◽  
pp. 49
Author(s):  
David Méndez-Luna ◽  
Loreley Araceli Morelos-Garnica ◽  
Juan Benjamín García-Vázquez ◽  
Martiniano Bello ◽  
Itzia Irene Padilla-Martínez ◽  
...  
Keyword(s):  
Binding Site ◽  
Cell Lines ◽  
Cancer Cell ◽  
Inhibitory Activity ◽  
In Silico ◽  
Cancer Cell Lines ◽  
Pancreatic Cancer Cells ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
New Compounds

The implementation of chemo- and bioinformatics tools is a crucial step in the design of structure-based drugs, enabling the identification of more specific and effective molecules against cancer without side effects. In this study, three new compounds were designed and synthesized with suitable absorption, distribution, metabolism, excretion and toxicity (ADME-tox) properties and high affinity for the G protein-coupled estrogen receptor (GPER) binding site by in silico methods, which correlated with the growth inhibitory activity tested in a cluster of cancer cell lines. Docking and molecular dynamics (MD) simulations accompanied by a molecular mechanics/generalized Born surface area (MMGBSA) approach yielded the binding modes and energetic features of the proposed compounds on GPER. These in silico studies showed that the compounds reached the GPER binding site, establishing interactions with a phenylalanine cluster (F206, F208 and F278) required for GPER molecular recognition of its agonist and antagonist ligands. Finally, a 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay showed growth inhibitory activity of compounds 4, 5 and 7 in three different cancer cell lines—MIA Paca-2, RCC4-VA and Hep G2—at micromolar concentrations. These new molecules with specific chemical modifications of the GPER pharmacophore open up the possibility of generating new compounds capable of reaching the GPER binding site with potential growth inhibitory activities against nonconventional GPER cell models.

Indole-3-carbinol inhibits the proliferation of colorectal carcinoma LoVo cells through activation of the apoptotic signaling pathway

2021 ◽  
pp. 096032712110214
Author(s):  
JY Lee ◽  
HM Lim ◽  
CM Lee ◽  
S-H Park ◽  
MJ Nam
Keyword(s):  
Colorectal Carcinoma ◽  
Cancer Cells ◽  
Inhibitory Activity ◽  
Annexin V ◽  
Fluorescein Isothiocyanate ◽  
Cell Counting ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Lovo Cells

Indole-3-carbinol (I3C) is a phytochemical that exhibits growth-inhibitory activity against various cancer cells. However, there are limited studies on the effects of I3C on colon cancer cells. In this study, the growth-inhibitory activity of I3C against the human colorectal carcinoma cell line (LoVo) was examined. The results of the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide, colony formation, and cell counting assays revealed that I3C suppressed the proliferation of LoVo cells. Microscopy and wound-healing analyses revealed that I3C affected the morphology and inhibited the migration of LoVo cells, respectively. I3C induced apoptosis and DNA fragmentation as evidenced by the results of fluorescein isothiocyanate-conjugated annexin V staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling assay, respectively. Additionally, I3C arrested the cell cycle at the G0/G1 phase and enhanced the reactive oxygen species levels. Western blotting analysis revealed that treatment with I3C resulted in the activation of apoptotic proteins, such as poly(ADP-ribose) polymerase, caspase-3, caspase-7, caspase-9, Bax, Bim, and p53 in LoVo cells. These results indicate that I3C induces apoptosis in LoVo cells by upregulating p53, leading to the activation of Bax and caspases. Taken together, I3C exerts cytotoxic effects on LoVo cells by activating apoptosis.

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