scholarly journals Chemoreversal Agents from Taiwanofungus Genus and Their More Potent Methyl Derivatives Targeting Signal Transducer and Activator of Transcription 3 (STAT3) Phosphorylation

2021 ◽  
Vol 14 (9) ◽  
pp. 916
Author(s):  
Ko-Hua Yu ◽  
Chin-Chuan Hung ◽  
Tian-Shung Wu ◽  
Chin-Fu Chen ◽  
I-Ting Wu ◽  
...  
Keyword(s):  
Methyl Ester ◽  
Cancer Cells ◽  
Acid Methyl Ester ◽  
Signal Transducer ◽  
Collateral Sensitivity ◽  
Structure Activity ◽  
Acid Methyl ◽  
Stat3 Phosphorylation ◽  
Transcription 3 ◽  
Better Than

Multidrug resistance (MDR), for which the mechanisms are not yet fully clear, is one of the major obstacles to cancer treatment. In recent years, signal transducer and activator of transcription 3 (STAT3) were found to be one of the important MDR mechanism pathways. Based on the previous research, zhankuic acid A, B, and C were found to have collateral sensitivity effects on MDR cancer cells, and MDR inhibitory activity of zhankuic acid methyl ester was found to be better than that of its acid. Therefore, we executed a systematic examination of the structure–activity relationship of zhankuic acid methyl ester derivatives to collateral sensitivity in MDR cancer cells. The results showed that compound 12 is the best in terms of chemoreversal activity, where the reversal fold was 692, and the IC50 value of paclitaxel combined with 10 μM compound 12 treatment was 1.69 nM in MDR KBvin cells. Among all the derivatives, methyl ester compounds were found to be better than their acids, and a detailed discussion of the structure–activity relationships of all of the derivatives is provided in this work. In addition, compounds 8, 12, and 26 were shown to influence the activation of STAT3 in KBvin cells, accounting for part of their chemoreversal effects. Our results may provide a new combined therapy with paclitaxel to treat multidrug-resistant cancers and provide a new therapy option for patients.

scholarly journals Newly synthesized 3-(4-chloro-phenyl)-3-hydroxy-2,2-dimethyl-propionic acid methyl ester derivatives selectively inhibit the proliferation of colon cancer cells

RSC Advances ◽  
2020 ◽  
Vol 10 (15) ◽  
pp. 8825-8841
Author(s):  
Samir M. El Rayes ◽  
Ahmed Aboelmagd ◽  
Mohamed S. Gomaa ◽  
Walid Fathalla ◽  
Ibrahim A. I. Ali ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Methyl Ester ◽  
Cancer Cells ◽  
Propionic Acid ◽  
Acid Methyl Ester ◽  
Colon Cancer Cells ◽  
Structure Modification ◽  
Acid Methyl

A series of 24 compounds were synthesized based on structure modification of the model methyl-3-(4-chlorophenyl)-3-hydroxy-2,2-dimethylpropanoate as potent HDACIs.

scholarly journals Triterpenoids and Alkaloids from the Roots of Peganum Nigellastrum

2008 ◽  
Vol 3 (2) ◽  
pp. 1934578X0800300
Author(s):  
Zhongze Ma ◽  
Yoshio Hano ◽  
Feng Qiu ◽  
Gang Shao ◽  
Yingjie Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Methyl Ester ◽  
Cancer Cells ◽  
Acid Methyl Ester ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Pentacyclic Triterpenoids ◽  
Acid Methyl ◽  
Androgen Independent ◽  
Chemical Evidence

Four lupane-type triterpenoids (1–4) and seven alkaloids (5–11) were isolated from the roots of Peganum nigellastrum. On the basis of spectroscopic and chemical evidence, the structures of the compounds were elucidated as 3α-hydroxy-27- trans-caffeoyloxylup-20(29)-en-28-oic acid methyl ester (1), 3β-hydroxy-27- trans-caffeoyloxylup-20(29)-en-28-oic acid methyl ester (2), 3α-acetoxy-27- trans-caffeoyloxylup-20(29)-en-28-oic acid methyl ester (3), 3β-acetoxy-27- trans-caffeoyloxylup-20(29)-en-28-oic acid methyl ester (4), luotonin C (5), luotonin D (6), harmine (7), harmol (8), harmaline (9), deoxyvasicinone (10) and vasicinone (11). Compounds 1, 3 and 4 are novel triterpenoids, and these pentacyclic triterpenoids were evaluated for their cytotoxicity against the androgen-sensitive LNCaP and androgen-independent PC-3 human prostate cancer cells.

scholarly journals Acacetin Inhibits the Growth of STAT3-Activated DU145 Prostate Cancer Cells by Directly Binding to Signal Transducer and Activator of Transcription 3 (STAT3)

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6204
Author(s):  
Sun Yun ◽  
Yu-Jin Lee ◽  
Jiyeon Choi ◽  
Nam Doo Kim ◽  
Dong Cho Han ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Critical Role ◽  
Cancer Drug ◽  
Dependent Manner ◽  
Signal Transducer ◽  
Prostate Cancer Cells ◽  
Stat3 Phosphorylation ◽  
Transcription 3

Signal transducer and activator of transcription 3 (STAT3) plays a critical role in the formation and growth of human cancer. Therefore, STAT3 is a therapeutic target for cancer drug discovery. Acacetin, a flavone present in various plants, inhibits constitutive and inducible STAT3 activation in STAT3-activated DU145 prostate cancer cells. Acacetin inhibits STAT3 activity by directly binding to STAT3, which we confirmed by a pull-down assay with a biotinylated compound and two level-free methods, namely, a drug affinity responsive target stability (DARTS) experiment and a cellular thermal shift assay (CETSA). Acacetin inhibits STAT3 phosphorylation at the tyrosine 705 residue and nuclear translocation in DU145 cells, which leads to the downregulation of STAT3 target genes. Acacetin then induces apoptosis in a time-dependent manner. Interestingly, acacetin induces the production of reactive oxygen species (ROS) that are not involved in the acacetin-induced inhibition of STAT3 activation because the suppressed p-STAT3 level is not rescued by treatment with GSH or NAC, which are general ROS inhibitors. We also found that acacetin inhibits tumor growth in xenografted nude mice. These results suggest that acacetin, as a STAT3 inhibitor, could be a possible drug candidate for targeting STAT3 for the treatment of cancer in humans.

scholarly journals Rosmarinic Acid Methyl Ester Regulates Ovarian Cancer Cell Migration and Reverses Cisplatin Resistance by Inhibiting the Expression of Forkhead Box M1

2020 ◽  
Vol 13 (10) ◽  
pp. 302
Author(s):  
Soo Hyun Lim ◽  
Ki Hong Nam ◽  
Kyungtae Kim ◽  
Sang Ah Yi ◽  
Jaecheol Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Methyl Ester ◽  
Cancer Cells ◽  
Rosmarinic Acid ◽  
Target Genes ◽  
Acid Methyl Ester ◽  
Ovarian Cancer Cells ◽  
Forkhead Box ◽  
Acid Methyl ◽  
Forkhead Box M1

Rosmarinic acid methyl ester (RAME), a derivative of rosmarinic acid (RA), is reported to have several therapeutic effects, including anti-tumor effects against cervical cancer. However, its anti-tumor effects in ovarian cancer is unclear. In this study, we studied the molecular pathways associated with the anti-tumor effects of RAME in ovarian cancer. To identify the effects of RAME in ovarian cancer, RNA sequencing was performed in RAME-treated ovarian cancer cells; we found that RAME treatment downregulated the genes closely involved with the target genes of the transcription factor Forkhead box M1 (FOXM1). It was reported that FOXM1 is overexpressed in a variety of cancer cells and is associated with cell proliferation and tumorigenesis. Therefore, we hypothesized that FOXM1 is a key target of RAME; this could result in its anti-tumor effects. Treatment of ovarian cancer cells with RAME-inhibited cell migration and invasion, as shown by wound healing and transwell migration assays. To examine whether RAME represses the action of FOXM1, we performed quantitative RT-PCR and ChIP-qPCR. Treatment of ovarian cancer cells with RAME decreased the mRNA expression of FOXM1 target genes and the binding of FOXM1 to its target genes. Moreover, FOXM1 expression was increased in cisplatin-resistant ovarian cancer cells, and combination treatment with RAME and cisplatin sensitized the cisplatin-resistant ovarian cancer cells, which was likely due to FOXM1 inhibition. Our research suggests that RAME is a promising option in treating ovarian cancer patients, as it revealed a novel molecular pathway underlying its anti-tumor effects.

Acetyl glycyrrhetinic acid methyl ester as a promising glycyrrhizin derivative against the breast cancer cells (MCF-7)

2019 ◽  
Vol 8 (2) ◽  
pp. 161
Author(s):  
FaridA Badria ◽  
MohamedG Ibrahim ◽  
FardousF El-Senduny ◽  
MagdyM Youssef ◽  
DiaaeldinM Elimam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Methyl Ester ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Acid Methyl Ester ◽  
Glycyrrhetinic Acid ◽  
Acid Methyl ◽  
Mcf 7
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