The Anti-Cancer Effect of Linusorb B3 from Flaxseed Oil through the Promotion of Apoptosis, Inhibition of Actin Polymerization, and Suppression of Src Activity in Glioblastoma Cells

Linusorbs (LOs) are natural peptides found in flaxseed oil that exert various biological activities. Of LOs, LOB3 ([1–9-NαC]-linusorb B3) was reported to have antioxidative and anti-inflammatory activities; however, its anti-cancer activity has been poorly understood. Therefore, this study investigated the anti-cancer effect of LOB3 and its underlying mechanism in glioblastoma cells. LOB3 induced apoptosis and suppressed the proliferation of C6 cells by inhibiting the expression of anti-apoptotic genes, B cell lymphoma 2 (Bcl-2) and p53, as well as promoting the activation of pro-apoptotic caspases, caspase-3 and -9. LOB3 also retarded the migration of C6 cells, which was achieved by suppressing the formation of the actin cytoskeleton critical for the progression, invasion, and metastasis of cancer. Moreover, LOB3 inhibited the activation of the proto-oncogene, Src, and the downstream effector, signal transducer and activator of transcription 3 (STAT3), in C6 cells. Taken together, these results suggest that LOB3 plays an anti-cancer role by inducing apoptosis and inhibiting the migration of C6 cells through the regulation of apoptosis-related molecules, actin polymerization, and proto-oncogenes.

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Lycium barbarum polysaccharide induced apoptosis and inhibited proliferation in infantile hemangioma endothelial cells via down-regulation of PI3K/AKT signaling pathway

Bioscience Reports ◽

10.1042/bsr20191182 ◽

2019 ◽

Vol 39 (8) ◽

Cited By ~ 1

Author(s):

Lin Lou ◽

Guo Chen ◽

Bing Zhong ◽

Feng Liu

Keyword(s):

Endothelial Cells ◽

Biological Activities ◽

Quantitative Polymerase Chain Reaction ◽

B Cell Lymphoma ◽

Infantile Hemangioma ◽

Cell Counting ◽

Nuclear Antigen ◽

Lycium Barbarum ◽

Lycium Barbarum Polysaccharide ◽

Induced Apoptosis

Abstract Lycium barbarum polysaccharide (LBP) has a variety of pharmacological and biological activities such as anti-inflammatory, antioxidation, anti-apoptosis, immune regulation and other pharmacological effects; however, the effect of LBP on infantile hemangioma (IH) was less reported. Primary human hemangioma endothelial cells (HemECs) were isolated from fresh surgical specimens of patients. HemECs was treated with LBP and the changes in proliferative and apoptotic signaling pathways were investigated by performing cell counting kit-8, cloning formation experiment, in vitro angiogenesis experiment, flow cytometry, Western blot, immunofluorescence, HE stain and real-time quantitative polymerase chain reaction. We found that LBP potently inhibited the proliferation of HemECs and achieved a low-micromolar IC50 (45 and 40 μg/ml, the half maximal inhibitory concentration) value and less angiogenesis, however, the IC50 had no effect on human umbilical vein endothelial cells (HUVECs) viability. LBP treatment induced apoptosis in HemECs, which was supported by positive Annexin-V-FITC staining, the activation of cleaved caspase-3 and Bcl-2-associated X protein (Bax) and the inhibition of B-cell lymphoma/leukemia-2 (Bcl-2). Moreover, the result demonstrated that LBP suppressed the expressions of proliferating cell nuclear antigen (PCNA), Ki67, vascular endothelial growth factor (VEGF), VEGFR2 and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signal pathway. PI3K-specific agonist (IGF-1) had promotive effects on HemECs proliferation, which was reversed by LBP. Our study suggests that the effectiveness of LBP in IHs may be associated with its potent anti-proliferative and apoptotic activities in HemECs. Thus, our findings may provide an effective medicine for IHs treatment.

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Dehydroxyhispolon Methyl Ether, A Hispolon Derivative, Inhibits WNT/β-Catenin Signaling to Elicit Human Colorectal Carcinoma Cell Apoptosis

International Journal of Molecular Sciences ◽

10.3390/ijms21228839 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8839

Author(s):

Hueng-Chuen Fan ◽

Ya-Chu Hsieh ◽

Li-Hsuan Li ◽

Ching-Chin Chang ◽

Karolína Janoušková ◽

...

Keyword(s):

Methyl Ether ◽

Cell Apoptosis ◽

Ectopic Expression ◽

Annexin V ◽

B Cell Lymphoma ◽

Human Colon ◽

Underlying Mechanism ◽

Parp Cleavage ◽

Signaling Axis ◽

Induced Apoptosis

Colorectal cancer (CRC) is the fourth leading cause of cancer mortality worldwide. Aberrant activation of WNT/β-catenin signaling present in the vast majority of CRC cases is indispensable for CRC initiation and progression, and thus is a promising target for CRC therapeutics. Hispolon is a fungal-derived polyphenol with a pronounced anticancer effect. Several hispolon derivatives, including dehydroxyhispolon methyl ether (DHME), have been chemically synthesized for developing lead molecules with stronger anticancer activity. Herein, a DHME-elicited anti-CRC effect with the underlying mechanism is reported for the first time. Specifically, DHME was found to be more cytotoxic than hispolon against a panel of human CRC cell lines, while exerting limited toxicity to normal human colon cell line CCD 841 CoN. Additionally, the cytotoxic effect of DHME appeared to rely on inducing apoptosis. This notion was evidenced by DHME-elicited upregulation of poly (ADP-ribose) polymerase (PARP) cleavage and a cell population positively stained by annexin V, alongside the downregulation of antiapoptotic B-cell lymphoma 2 (BCL-2), whereas the blockade of apoptosis by the pan-caspase inhibitor z-VAD-fmk attenuated DHME-induced cytotoxicity. Further mechanistic inquiry revealed the inhibitory action of DHME on β-catenin-mediated, T-cell factor (TCF)-dependent transcription activity, suggesting that DHME thwarted the aberrantly active WNT/β-catenin signaling in CRC cells. Notably, ectopic expression of a dominant–active β-catenin mutant (∆N90-β-catenin) abolished DHME-induced apoptosis while also restoring BCL-2 expression. Collectively, we identified DHME as a selective proapoptotic agent against CRC cells, exerting more potent cytotoxicity than hispolon, and provoking CRC cell apoptosis via suppression of the WNT/β-catenin signaling axis.

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Carnosol induces apoptotic cell death through ROS-dependent inactivation of STAT3 in human melanoma G361 cells

Applied Biological Chemistry ◽

10.1186/s13765-019-0463-z ◽

2019 ◽

Vol 62 (1) ◽

Cited By ~ 1

Author(s):

Seung Mi Choi ◽

Do-Hee Kim ◽

Kyung-Soo Chun ◽

Joon-Seok Choi

Keyword(s):

B Cell ◽

Molecular Mechanisms ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Human Melanoma ◽

Dependent Manner ◽

Bax Protein ◽

Wide Range ◽

Anti Cancer ◽

Induced Apoptosis

Abstract Melanoma is the leading cause of skin cancer deaths, and the poor prognosis of metastatic melanoma has made needs for a novel pharmacological treatment or efficient intervention. Carnosol, a major polyphenolic compound from Rosmarinus officinalis, has a wide range of biological activities including anti-cancer effect. However, the underlying molecular mechanisms of its anti-cancer effect remain poorly understood in malignant human melanoma cells. In the present study, we investigate the apoptotic effect and the underlying anti-cancer mechanisms of carnosol. Our results revealed that carnosol strongly induced apoptosis against human melanoma G361 cells in a dose- and time-dependent manner, and caused dramatical elevation in cellular reactive oxygen species (ROS) level during apoptosis. In mechanistic studies, carnosol treatment decreased protein level of anti-apoptotic B‑cell lymphoma 2 (Bcl-2) and B cell lymphoma-extra large (Bcl-xL), however, increased level of pro-apoptotic Bcl-2-associated X protein (Bax) protein. Moreover, carnosol escalated cellular level of p53, which was accompanied by a decline of mouse double minute 2 homolog (MDM2) level. Also, carnosol inhibited activation of Src and signal transducer and activator of transcription 3 (STAT3), therefore down-regulated STAT3-dependent gene expression, such as D-series cyclin and survivin. These changes by carnosol were attenuated by pre-treatment of N-acetyl cysteine, and abolished progression of carnosol-induced apoptosis. In conclusion, carnosol induced apoptosis in human melanoma G361 cells through ROS generation and inhibition of STAT3-mediated pathway. Our results provide molecular bases of carnosol-induced apoptosis, and suggest a novel candidate for human melanoma treatment.

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Biosynthesis of Lemongrass Essential Oil and the Underlying Mechanism for Its Insecticidal Activity

10.20944/preprints202009.0276.v1 ◽

2020 ◽

Author(s):

Mohammad Mukarram ◽

M. Masroor A. Khan ◽

Andleeb Zehra ◽

Sadaf Choudhary ◽

Tariq Aftab ◽

...

Keyword(s):

Essential Oil ◽

Synergistic Effects ◽

Biological Activities ◽

Perennial Grass ◽

Underlying Mechanism ◽

Cymbopogon Flexuosus ◽

Anti Cancer ◽

Lemongrass Oil ◽

Cytotoxic Responses ◽

Lemongrass Essential Oil

Lemongrass (Cymbopogon flexuosus) is an aromatic perennial grass grown extensively for its essential oil. Lemongrass oil is chiefly a mixture of various cyclic and acyclic bioactive monoterpenes. We reviewed lemongrass oil and its biosynthesis in the present chapter along with its biochemical composition. Furthermore, we attempted to explore both the possible routes for essential oil biosynthesis in lemongrass, i.e. mevalonate and non-mevalonate pathways and how these pathways interwind with each other. Lemongrass oil has high commercial potential in medicinal, cosmetic, food and energy industries. Regarding the pharmacological properties, a wide array of biological activities has been observed in lemongrass oil such as antimicrobial, insecticidal, analgesic and anti-cancer properties as well as its efficacy as insect-repellent. The later sections were dedicated for the analysis of insecticidal property of the lemongrass oil and the mechanism working behind this phenomenon where it was observed that in addition to synergistic effects, various components of lemongrass oil can also induce specific neurotoxic and cytotoxic responses in the insects.

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2,5-Hexanedione induced apoptosis in rat spinal cord neurons and VSC4.1 cells via the proNGF/p75NTR and JNK pathways

Bioscience Reports ◽

10.1042/bsr20204264 ◽

2021 ◽

Author(s):

Mengxin Luo ◽

Xiaoxia Shi ◽

Qi Guo ◽

Shuangyue Li ◽

Qing Zhang ◽

...

Keyword(s):

Neuronal Apoptosis ◽

B Cell Lymphoma ◽

Underlying Mechanism ◽

Neurotrophin Receptor ◽

P75 Neurotrophin Receptor ◽

Sprague Dawley ◽

Spinal Cord Neurons ◽

Sd Rats ◽

Induced Apoptosis

Increasing evidence suggests that n-hexane induces nerve injury via neuronal apoptosis induced by its active metabolite 2,5-hexanedione (HD). However, the underlying mechanism remains unknown. Studies have confirmed that pro-nerve growth factor (proNGF), a precursor of mNGF, might activate apoptotic signaling by binding to p75 neurotrophin receptor (p75NTR) in neurons. Therefore, we studied the mechanism of the proNGF/p75NTR pathway in HD-induced neuronal apoptosis. Sprague Dawley (SD) rats were injected with 400 mg/kg HD once a day for 5 weeks, and VSC4.1 cells were treated with 10, 20, and 40 mM HD in vitro. Results showed that HD effectively induced neuronal apoptosis. Moreover, it upregulated proNGF and p75NTR levels, activated c-Jun N-terminal kinase (JNK) and c-Jun, and disrupted the balance between B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax). Our findings revealed that the proNGF/p75NTR signaling pathway was involved in HD-induced neuronal apoptosis; they can serve as a theoretical basis for further exploration of the neurotoxic mechanisms of HD.

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Investigating the in Vitro Antiproliferative and Apoptosis-Inducing Effects of Pyranochromene Derivatives

Biointerface Research in Applied Chemistry ◽

10.33263/briac113.1098710995 ◽

2020 ◽

Vol 11 (3) ◽

pp. 10987-10995

Keyword(s):

Cell Lines ◽

Biological Activities ◽

Para Position ◽

Lead Compounds ◽

Three Component Reaction ◽

Anti Cancer ◽

Important Health ◽

Induced Apoptosis ◽

Mcf 7

Cancer is one of the important health problems, and researchers continue their efforts to discover new anti-cancer agents. Coumarins (chromene-2-ones), a group of natural metabolites, have shown different biological activities based on their substitutions. In this study, 15 compounds of 1,5-dihydropyrano[2,3-c]chromene were synthesized by three-component reaction and investigated for the antiproliferative activity on the breast (MCF-7), colorectal (SW48 and HT-29), lung (A549), and brain (U-87 MG) cancer cell lines as well as two normal cell lines (3T3 and HUVEC). The apoptosis/necrosis-inducing effect of the selected compounds was determined on the MCF-7 cell line by flow cytometry. The results showed that the compounds bearing a moiety on their phenyl ring's para position had potent cytotoxic effects on the tested cell lines. These compounds induced apoptosis in MCF-7 cells. The compounds were also toxic for 3T3 and HUVECs and did not display a high selectivity for tumor cells. Our results revealed that the compounds having a moiety at the para position of their phenyl ring might be suitable lead compounds for the synthesis of potent anti-cancer agents.

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ANTICANCER EFFECT OF UVARIA GENUS

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2013.6.16 ◽

2014 ◽

pp. 98-101

Author(s):

Thi Bich Hien Le ◽

Viet Duc Ho ◽

Thi Hoai Nguyen

Keyword(s):

Biological Activities ◽

Current Trend ◽

Healthcare Systems ◽

Chemical Compositions ◽

Cancer Therapies ◽

Pharmacological Effects ◽

Anticancer Effect ◽

Anti Cancer ◽

Tropical Areas ◽

Cancer Activity

Nowadays, cancer treatment has been a big challenge to healthcare systems. Most of clinical anti-cancer therapies are toxic and cause adverse effects to human body. Therefore, current trend in science is seeking and screening of natural compounds which possess antineoplastic activities to utilize in treatment. Uvaria L. - Annonaceae includes approximately 175 species spreading over tropical areas of Asia, Australia, Africa and America. Studies on chemical compositions and pharmacological effects of Uvaria showed that several compound classes in this genus such as alkaloid, flavonoid, cyclohexen derivaties, acetogenin, steroid, terpenoid, etc. indicate considerable biological activities, for example anti-tumor, anti-cancer, antibacterial, antifungal, antioxidant, etc. Specifically, anti-cancer activity of fractions of extract and pure isolated compounds stands out for cytotoxicity against many cancer cell lines. This study provides an overview of anti-cancer activity of Uvaria and suggests a potential for further studies on seeking and developing novel anti-cancer compounds. Key words: Anti-cancer, Uvaria.

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Structure-Bioactivity Relationship Study of Xanthene Derivatives: A Brief Review

Current Organic Synthesis ◽

10.2174/1570179416666191017094908 ◽

2020 ◽

Vol 16 (8) ◽

pp. 1071-1077

Author(s):

Aref G. Ghahsare ◽

Zahra S. Nazifi ◽

Seyed M.R. Nazifi

Keyword(s):

Biological Activities ◽

Cyclic Compound ◽

Research Field ◽

Pharmaceutical Chemistry ◽

Therapeutic Effects ◽

Main Research ◽

Research Fields ◽

Xanthene Derivatives ◽

Anti Cancer ◽

Heterocyclic Derivatives

: Over the last decades, several heterocyclic derivatives compounds have been synthesized or extracted from natural resources and have been tested for their pharmaceutical activities. Xanthene is one of these heterocyclic derivatives. These compounds consist of an oxygen-containing central heterocyclic structure with two more cyclic structures fused to the central cyclic compound. It has been shown that xanthane derivatives are bioactive compounds with diverse activities such as anti-bacterial, anti-fungal, anti-cancer, and anti-inflammatory as well as therapeutic effects on diabetes and Alzheimer. The anti-cancer activity of such compounds has been one of the main research fields in pharmaceutical chemistry. Due to this diverse biological activity, xanthene core derivatives are still an attractive research field for both academia and industry. This review addresses the current finding on the biological activities of xanthene derivatives and discussed in detail some aspects of their structure-activity relationship (SAR).

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Synthesis of Indolyl Pyrazole Scaffolds as Potential Anti-cancer Agents and their Molecular Modelling Studies

Letters in Drug Design & Discovery ◽

10.2174/1570180816666191024103534 ◽

2020 ◽

Vol 17 (7) ◽

pp. 828-839

Author(s):

Ganga Reddy Gaddam ◽

Pramod Kumar Dubey ◽

Venkata Ramana Reddy Chittireddy

Keyword(s):

Cell Lines ◽

Biological Activities ◽

Moderate Activity ◽

Lung Cancer Cell ◽

Anti Cancer ◽

A549 Lung Cancer Cell ◽

New Chemical Entities ◽

Molecular Modelling Studies ◽

Modelling Studies ◽

A549 Lung

Background:: Indole and pyrazoles are one of the prime structural units in the field of medicinal chemistry and have been reported to exhibit a variety of biological activities specifically anti-cancer. In view of their medicinal significance, we synthesized a conjugate of the two moieties to get access to newer and potential anti-cancer agents. Methods: Indolyl pyrazoles [3-(1,3-diphenyl-1H-pyrazol-4-yl)-2-(1-methyl-1H-indole-3-carbon yl)acrylonitriles] (4a-l) were synthesized by adopting simple and greener protocol and all the synthesized derivatives were docked against Bcl-2 protein and the selected chemical moieties were screened for their cytotoxicity by using the MTT assay. Results: : All the synthesized compounds were docked against BCL-2 protein in order to understand their binding pattern. Among the 12 compounds docked, 4d, 4f, 4h, 4j, and 4l compounds exhibited better protein binding interactions and the same were screened for their anti-cancer activity against A549 (lung) cancer cell lines at a concentration of 100 μM using Doxorubicin as standard. Substitutions such as N-benzyl, N-ethyl groups and halogen groups such as Br, Cl on indole ring showed moderate activity against A-549 cell lines. Conclusion:: Among the 5 indolyl pyrazole derivatives screened, compounds 4h and 4j showed significantly better activity with an IC50 of 33.12 and 34.24 μM, respectively. Further, structural tweaking of the synthesized new chemical entities may lead to potential hit/lead-like molecules.

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Natural Sesquiterpene Lactones in the Prevention and Treatment of Inflammatory Disorders and cancer: A Systematic Study of this Emerging Therapeutic Approach based on Chemical and Pharmacological Aspect

Letters in Drug Design & Discovery ◽

10.2174/1570180817999200421144007 ◽

2020 ◽

Vol 17 (9) ◽

pp. 1102-1116

Author(s):

Sudip Kumar Mandal ◽

Utsab Debnath ◽

Amresh Kumar ◽

Sabu Thomas ◽

Subhash Chandra Mandal ◽

...

Keyword(s):

Drug Discovery ◽

Biological Activities ◽

Sesquiterpene Lactones ◽

Structural Diversity ◽

Cancer Drug ◽

Cancer Drug Discovery ◽

Anti Cancer ◽

Drug Discovery Program ◽

Anti Inflammatory ◽

Family Based

Background and Introduction: Sesquiterpene lactones are a class of secondary metabolite that contains sesquiterpenoids and lactone ring as pharmacophore moiety. A large group of bioactive secondary metabolites such as phytopharmaceuticals belong to this category. From the Asteraceae family-based medicinal plants, more than 5,000 sesquiterpene lactones have been reported so far. Sesquiterpene lactone-based pharmacophore moieties hold promise for broad-spectrum biological activities against cancer, inflammation, parasitic, bacterial, fungal, viral infection and other functional disorders. Moreover, these moiety based phytocompounds have been highlighted with a new dimension in the natural drug discovery program worldwide after the 2015 Medicine Nobel Prize achieved by the Artemisinin researchers. Objective: These bitter substances often contain an α, β-unsaturated-γ-lactone as a major structural backbone, which in recent studies has been explored to be associated with anti-tumor, cytotoxic, and anti-inflammatory action. Recently, the use of sesquiterpene lactones as phytomedicine has been increased. This study will review the prospect of sesquiterpene lactones against inflammation and cancer. Methods: Hence, we emphasized on the different features of this moiety by incorporating its structural diversity on biological activities to explore structure-activity relationships (SAR) against inflammation and cancer. Results: How the dual mode of action such as anti-inflammatory and anti-cancer has been exhibitedby these phytopharmaceuticals will be forecasted in this study. Furthermore, the correlation of anti-inflammatory and anti-cancer activity executed by the sesquiterpene lactones for fruitful phytotherapy will also be revealed in the present review in the milieu of pharmacophore activity relation and pharmacodynamics study as well. Conclusion: So, these metabolites are paramount in phytopharmacological aspects. The present discussion on the future prospect of this moiety based on the reported literature could be a guide for anti-inflammatory and anti-cancer drug discovery programs for the upcoming researchers.

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