PHENYLPROPANOIDS, EUGENOL SCAFFOLD, AND ITS DERIVATIVES AS ANTICANCER

ABSTRACTEugenol (EU) is a phenylpropene, an allyl chain-substituted guaiacol. EU is a member of the phenylpropanoids class of chemical compounds. It is acolorless to pale yellow oily liquid extracted from certain essential oils especially from clove oil. Further, chemopreventive agents might be used singlyor in combination with chemotherapy or radiotherapy for the more effective treatment of cancer by enhancing the efficacy of these modalities withminimal side effects and toxicity. Considering that EU scaffold may be a prospective chemopreventive agent, its potent antitumor ability to interferewith solid cancer cell growth and its molecular mechanism were evaluated as an initiative toward the development of a novel strategy for cancertreatment. This review article will conduct that EU as the antiproliferative activity and molecular mechanism of the EU induced apoptosis against thecancer cells and animal models.Keywords: Eugenol, Derivatives of eugenol, Scaffold, Anticancer, Phenylpropanoids.

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DGG-100629 inhibits lung cancer growth by suppressing the NFATc1/DDIAS/STAT3 pathway

Experimental & Molecular Medicine ◽

10.1038/s12276-021-00601-2 ◽

2021 ◽

Author(s):

Joo-Young Im ◽

Bo-Kyung Kim ◽

Sung-Hoon Yoon ◽

Byoung Chul Cho ◽

Yu Mi Baek ◽

...

Keyword(s):

Lung Cancer ◽

Cell Growth ◽

Cancer Cell ◽

Target Genes ◽

Nuclear Translocation ◽

Lung Cancer Cell ◽

Chemical Library ◽

Cancer Cell Growth ◽

Novel Strategy ◽

Induced Apoptosis

AbstractDNA damage-induced apoptosis suppressor (DDIAS) promotes the progression of lung cancer and hepatocellular carcinoma through the regulation of multiple pathways. We screened a chemical library for anticancer agent(s) capable of inhibiting DDIAS transcription. DGG-100629 was found to suppress lung cancer cell growth through the inhibition of DDIAS expression. DGG-100629 induced c-Jun NH(2)-terminal kinase (JNK) activation and inhibited NFATc1 nuclear translocation. Treatment with SP600125 (a JNK inhibitor) or knockdown of JNK1 restored DDIAS expression and reversed DGG-100629-induced cell death. In addition, DGG-100629 suppressed the signal transducer and activator of transcription (STAT3) signaling pathway. DDIAS or STAT3 overexpression restored lung cancer cell growth in the presence of DGG-100629. In a xenograft assay, DGG-100629 inhibited tumor growth by reducing the level of phosphorylated STAT3 and the expression of STAT3 target genes. Moreover, DGG-100629 inhibited the growth of lung cancer patient-derived gefitinib-resistant cells expressing NFATc1 and DDIAS. Our findings emphasize the potential of DDIAS blockade as a therapeutic approach and suggest a novel strategy for the treatment of gefitinib-resistant lung cancer.

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Potential Therapeutic Targets of Curcumin, Most Abundant Active Compound of Turmeric Spice: Role in the Management of Various Types of Cancer

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892815999201102214602 ◽

2020 ◽

Vol 15 ◽

Author(s):

Saleh A. Almatroodi ◽

Mansoor Ali Syed ◽

Arshad Husain Rahmani

Keyword(s):

Clinical Trials ◽

Cancer Cells ◽

Active Compound ◽

Molecular Mechanisms ◽

Human Subjects ◽

Cell Signalling ◽

Chemopreventive Agents ◽

Signalling Molecules ◽

Cancer Management ◽

Induced Apoptosis

Background:: Curcumin, an active compound of turmeric spice is one of the most-studies natural compounds and have been widely recognized as chemopreventive agents. Several molecular mechanisms have been proven, curcumin and its analogs play a role in cancer prevention through modulating various cell signaling pathways as well as inhibition of carcinogenesis process. Objective:: To study the potential role of curcumin in the management of various types of cancer through modulating cell signalling molecules based on available literature and recent patents. Methods:: A wide-ranging literature survey was performed based on Scopus, PubMed, PubMed central and Google scholar for the implication of curcumin in cancer management along with special emphasis on human clinical trials. Moreover, patents were searched through www.google.com/patents, www.freepatentsonline.com and www.freshpatents.com. Result:: Recent studies based on cancer cells have proven that curcumin have potential effects against cancer cells, prevent the growth of cancer and act as cancer therapeutic agents. Besides, curcumin exerted anticancer effects through inducing apoptosis, activating tumor suppressor genes, cell cycle arrest, inhibiting tumor angiogenesis, initiation, promotion and progression stages of tumor. It was established that co-treatment of curcumin and anti-cancer drugs could induce apoptosis and also play a significant role in the suppression of the invasion and metastasis of cancer cells. Conclusion:: Accumulating evidences suggest that curcumin has potentiality to inhibit cancer growth, induced apoptosis and modulate various cell signalling pathways molecules. Well-designed clinical trials of curcumin based on human subjects are still needed to establish the bioavailability, mechanism of action, efficacy and safe dose in the management of various cancers.

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Hybridized Quinoline Derivatives as Anticancer Agents: Design, Synthesis, Biological Evaluation and Molecular Docking

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666181112121058 ◽

2019 ◽

Vol 19 (4) ◽

pp. 439-452 ◽

Cited By ~ 3

Author(s):

Mohamed R. Selim ◽

Medhat A. Zahran ◽

Amany Belal ◽

Moustafa S. Abusaif ◽

Said A. Shedid ◽

...

Keyword(s):

Cell Cycle ◽

Anticancer Agents ◽

Caspase 3 ◽

Biological Evaluation ◽

Tubulin Polymerization ◽

Design Synthesis ◽

Chemical Structures ◽

M Phase ◽

Induced Apoptosis ◽

Derivatives Of

Objective: Conjugating quinolones with different bioactive pharmacophores to obtain potent anticancer active agents. Methods: Fused pyrazolopyrimidoquinolines 3a-d, Schiff bases 5, 6a-e, two hybridized systems: pyrazolochromenquinoline 7 and pyrazolothiazolidinquinoline 8, different substituted thiazoloquinolines 13-15 and thiazolo[3,2-a]pyridine derivatives 16a-c were synthesized. Their chemical structures were characterized through spectral and elemental analysis, cytotoxic activity on five cancer cell lines, caspase-3 activation, tubulin polymerization inhibition and cell cycle analysis were evaluated. Results: Four compounds 3b, 3d, 8 and 13 showed potent activity than doxorubicin on HCT116 and three compounds 3b, 3d and 8 on HEPG2. These promising derivatives showed increase in the level of caspase-3. The trifloromethylphenyl derivatives of pyrazolopyrimidoquinolines 3b and 3d showed considerable tubulin polymerization inhibitory activity. Both compounds arrested cell cycle at G2/M phase and induced apoptosis. Conclusion: Compounds 3b and 3d can be considered as promising anticancer active agents with 70% of colchicine activity on tubulin polymerization inhibition and represent hopeful leads that deserve further investigation and optimization.

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Stachyose-induced apoptosis of Caco-2 cells via the caspase-dependent mitochondrial pathway

Food & Function ◽

10.1039/c4fo01017e ◽

2015 ◽

Vol 6 (3) ◽

pp. 765-771 ◽

Cited By ~ 15

Author(s):

Guidong Huang ◽

Jian Mao ◽

Zhongwei Ji ◽

Aisikaer Ailati

Keyword(s):

Colon Cancer ◽

Cell Growth ◽

Cancer Cell ◽

Mitochondrial Pathway ◽

Colon Cancer Cell ◽

Cancer Cell Growth ◽

Induced Apoptosis

Some studies have shown that stachyose, as prebiotics, can prevent indirectly colon cancer cell growth by promoting the proliferation of probiotics or producing beneficial materials in the intestine.

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Aldo-Keto Reductase 1C3 Mediates Chemotherapy Resistance in Esophageal Adenocarcinoma via ROS Detoxification

Cancers ◽

10.3390/cancers13102403 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2403

Author(s):

Chenghui Zhou ◽

Zhefang Wang ◽

Jiahui Li ◽

Xiaolin Wu ◽

Ningbo Fan ◽

...

Keyword(s):

Esophageal Adenocarcinoma ◽

Mrna Level ◽

Chemotherapy Resistance ◽

Poor Overall Survival ◽

Akt Phosphorylation ◽

Tumor Tissues ◽

Novel Strategy ◽

Induced Apoptosis ◽

First Time ◽

Eac Cells

Esophageal adenocarcinoma (EAC) is one of the most lethal malignancies, and limits promising treatments. AKR1C3 represents a therapeutic target to combat the resistance in many cancers. However, the molecular mechanism of AKR1C3 in the chemotherapy resistance of EAC is still unclear. We found that the mRNA level of AKR1C3 was higher in EAC tumor tissues, and that high AKR1C3 expression might be associated with poor overall survival of EAC patients. AKR1C3 overexpression decreased cell death induced by chemotherapeutics, while knockdown of AKR1C3 attenuated the effect. Furthermore, we found AKR1C3 was inversely correlated with ROS production. Antioxidant NAC rescued chemotherapy-induced apoptosis in AKR1C3 knockdown cells, while the GSH biosynthesis inhibitor BSO reversed a protective effect of AKR1C3 against chemotherapy. AKT phosphorylation was regulated by AKR1C3 and might be responsible for eliminating over-produced ROS in EAC cells. Intracellular GSH levels were modulated by AKR1C3 and the inhibition of AKT could reduce GSH level in EAC cells. Here, we reported for the first time that AKR1C3 renders chemotherapy resistance through controlling ROS levels via AKT signaling in EAC cells. Targeting AKR1C3 may represent a novel strategy to sensitize EAC cells to conventional chemotherapy.

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RNAIII Inhibiting Peptide (RIP) and Derivatives as Potential Tools for the Treatment of S. aureus Biofilm Infections

Current Topics in Medicinal Chemistry ◽

10.2174/1568026618666181022120711 ◽

2019 ◽

Vol 18 (24) ◽

pp. 2068-2079 ◽

Cited By ~ 4

Author(s):

Michele Ciulla ◽

Antonio Di Stefano ◽

Lisa Marinelli ◽

Ivana Cacciatore ◽

Giuseppe Di Biase

Keyword(s):

Medical Devices ◽

Biofilm Formation ◽

Heart Valves ◽

Cell Communication ◽

Antibiofilm Activity ◽

Host Immune System ◽

Excellent Growth ◽

Potential Applications ◽

Novel Strategy ◽

Derivatives Of

S. aureus under the biofilm mode of growth is often related to several nosocomial infections, more frequently associated with indwelling medical devices (catheters, prostheses, portacaths or heart valves). As a biofilm, the biopolymer matrix provides an excellent growth medium, increasing the tolerance to antibiotics and host immune system. To date, the antimicrobial therapy alone is not effective. A novel strategy to prevent biofilm formation is based on the interference with the bacterial cell–cell communication, a process known as quorum sensing (QS) and mediated by the RNA-III-activating peptide (RAP) and its target protein TRAP (Target of RAP). The RNAIII inhibiting peptide (RIP) is able to inhibit S. aureus pathogenesis by disrupting QS mechanism competing with RAP, thus inhibiting the phosphorylation of TRAP. This alteration leads to a reduced adhesion and to the inhibition of RNAIII synthesis, with the subsequent suppression of toxins synthesis. The present paper will provide an overview on the activity and potential applications of RIP as biofilm inhibiting compound, useful in the management of S. aureus biofilm infections. Moreover, medicinal chemistry strategies have been examined to better understand which modifications and/or structure alterations were able to produce new derivatives of this QS inhibitor with an improved antibiofilm activity.

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ACACIA HONEY INDUCES APOPTOSIS IN HUMAN BREAST ADENOCARCINOMA CELL LINES (MCF-7)

Jurnal Teknologi ◽

10.11113/jt.v79.9882 ◽

2017 ◽

Vol 79 (4) ◽

Author(s):

Muhammad Ashraf Mohd Salleh ◽

Zolkapli Eshak ◽

Wan Iryani Wan Ismail

Keyword(s):

Antioxidant Properties ◽

Breast Adenocarcinoma ◽

Total Phenolic ◽

Flavonoid Content ◽

Cell Shrinkage ◽

Cancer Cell Growth ◽

Breast Cancer Cell Growth ◽

Acacia Honey ◽

Induced Apoptosis ◽

Mcf 7

Apoptosis is one of markers considered in drug design including in treating cancers. Conventional treatments for cancer cause various side effects. One of possible alternatives is honey, an antioxidant driven by its phenolic and flavonoids content. This study aims to observe the effects of Malaysian Acacia honey in inhibiting breast cancer cell growth through apoptosis. Antioxidant properties of the honey were measured using total phenolic content (TPC) and total flavonoid content (TFC). Then, antiproliferative activity of the honey were observed using MTT assay. The honey exhibited IC50 at concentration of 5.5% (v/v). Further studies using TUNEL and live cell view revealed that Acacia honey induced apoptosis after 6 hours of treatment. Cell shrinkage, which is one of the apoptotic features, was observed as early as 2 hours, followed by the formation of apoptotic bodies within 6 hours of the honey treatment. Details of mechanism and actual compounds involved in displaying the results are being intensively studied.

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Caspase-2 is activated at the CD95 death-inducing signaling complex in the course of CD95-induced apoptosis

Blood ◽

10.1182/blood-2005-07-007096 ◽

2006 ◽

Vol 108 (2) ◽

pp. 559-565 ◽

Cited By ~ 46

Author(s):

Inna N. Lavrik ◽

Alexander Golks ◽

Simone Baumann ◽

Peter H. Krammer

Keyword(s):

B Cell ◽

Molecular Mechanism ◽

Cell Lines ◽

Caspase 8 ◽

Signaling Complex ◽

Deficient Cell ◽

Apoptotic Pathways ◽

Caspase 2 ◽

Induced Apoptosis

Caspase-2 was reported to be involved in a number of apoptotic pathways triggered by various stimuli. However, the molecular mechanism of procaspase-2 activation in the course of apoptosis remains poorly defined. In this report, we demonstrate that procaspase-2 is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex (DISC) in human T- and B-cell lines. We show that procaspase-2 is activated at the DISC on CD95 stimulation. Despite its presence at the DISC, caspase-2 does not initiate apoptosis on CD95 stimulation in caspase-8–deficient cell lines. Taken together, our data reveal that caspase-2 is activated at the DISC but does not play an initiating role in the CD95-induced apoptosis.

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