Apoptosis-inducing Effect of Hydroquinone 5-O-Cinnamoyl Ester Analog of Renieramycin M on Non-small Cell Lung Cancer Cells

Maiuthed, Arnatchai; Pinkhien, Tatchakorn; Chamni, Supakarn; Suwanborirux, Khanit; Saito, Naoki; Petpiroon, Nareerat; Chanvorachote, Pithi

doi:10.21873/anticanres.12077

Cited by 8 publications

(9 citation statements)

References 26 publications

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“…In addition, 5b increased caspase-3 protein expression (Figure 3F), an important effector protease of both the intrinsic and extrinsic pathways of apoptosis, which is generally activated by chemotherapeutic drugs (20,21). Increased apoptosis and caspase-3 expression following treatment with cinnamoyl and benzaldehyde derivatives in different types of cancer, including leukemia cells, have been reported (6,(33)(34)(35). Finally, increased Fas death receptor expression (Figure 3E) and increased Bax/Bcl-2 ratio (Table II 19).…”

Section: Discussionmentioning

confidence: 87%

Synthesis and Biological Evaluation of Cyclic Analogues from Nitrone LQB-278: A New Potential Antileukemia Compound

et al. 2021

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Background/Aim: A new set of LQB-nitrones and analogues was synthesized to evaluate anticancer activity based on the substitution of the terpenyl moiety of the antileukemic compound LQB-278 by the conformationally restricted cinnamyl ether. Materials and Methods: A structure-activity relationship study was performed in vitro on Jurkat cells to screen the antileukemic activity of LQB-nitrones and analogues and elucidate the mechanisms of action of the most active derivatives. Results: The cynamyl ramification and its ortho position aldehyde substitution improved the antileukemic activity. Three compounds showed an in vitro antiproliferative action, but only 5b induced apoptosis. Analysis of the molecular mechanisms showed increased expression of the cell cycle inhibitor p21CIP1/WAF1/Sdi1, caspase 3, Fas receptor, and Bax/Bcl-2 ratio. Conclusion: The cinnamyl derivative 5b (LQB-461) presented higher antileukemic effects than the prototype terpenyl nitrone, inducing Jurkat cell death by activating both extrinsic and intrinsic pathways of apoptosis. Therefore, this compound is a new promising candidate drug against leukemia.In a previous work, we reported the effects of O-isoprenylated-N-methylnitrones, derived from hydroxybenzaldehydes, on different tumor cell lines, and the most effective compound was the O-geranylated-N-methylnitrone 1 (LQB-278) (1), a conjugated molecule, which presents a great conformational liberty in the terpenyl branch. Constraining the conformation of

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Section: Discussionmentioning

confidence: 87%

Synthesis and Biological Evaluation of Cyclic Analogues from Nitrone LQB-278: A New Potential Antileukemia Compound

et al. 2021

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“…Anoikis resistance is (CIN-RM), a newlysynthesized derivative of RM, has been shown to be more cytotoxic against non-small cell lung cancer cells compared to RM. CIN-RM treatment induced apoptosis by increasing apoptosis inducing factor and by activating of caspase 3 and 9 through a p53-dependent mechanism (92). Another study has reported the formation of bishydroquinone renieramycin M (HQ-RM) by modifying the quinone ring of RM.…”

Section: The Preclinical and Clinical Trials Of Cancer Therapy Using mentioning

confidence: 99%

Therapeutic Application of Diverse Marine-derived Natural Products in Cancer Therapy

Yun

Kim

2019

Anticancer Res

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Natural products (NPs) are useful sources of bioactive compounds and play important roles in the development and discovery of new drugs for diverse human diseases. Most natural products originate from terrestrial species, but diverse marine organisms are another source of new agents for cancer therapy. Natural products derived from marine organisms show diverse pharmacological activities via bioactive secondary metabolites. They regulate biological activities, such as cell proliferation, cell viability, induction of ROS production, ER stress, and apoptosis via modulation of cellular mechanisms in many cancers. Many natural products isolated from marine species require further study to elucidate the efficacy of their biological activity and anticancer effects. In this review, we summarize the biological properties and anticancer effects of diverse natural products extracted from marine organisms and their roles in tumor therapy. Cancer is one of the leading causes of death and an economic burden worldwide (1). Cancer involves an abnormal proliferation of cells and tissues, and is affected by various risk factors such as age, diet, genetics, and environmental factors (2, 3). It is also caused by the mutation of several cancer-related genes called tumor suppressors and oncogenes (4). Cancer also presents the ability of metastasis and recurrence, which are difficult to treat (5). Although conventional anticancer therapy includes both chemotherapy to induce apoptosis of target cancer cells and surgical therapy to remove tumors, these methods are limited by issues of therapeutic efficacy, safety, and side effects. Thus, it is necessary to develop novel strategies for cancer therapy, and natural products (NPs) are a promising source for novel drug development because they show diverse biological activities and anticancer effects via inhibition of tumor growth by interacting with several signaling pathways (6, 7). NPs have been a useful source of bioactive compounds and play an important role in the discovery and development of drugs. Most NPs, originated from terrestrial microbes, fungi, and plants, have been discovered to possess many pharmacologically active factors and used to treat several human diseases. Some of these are utilized as clinically valuable drugs for anticancer therapy (8-10). However, marine organisms have recently attracted substantial attention because 70% of the earth is covered by water, representing 95% of biodiversity (11-13). NPs derived from marine organisms have been researched for novel bioactive secondary metabolites due to their diverse pharmacological activities. Marine environments are estimated to harbor more than one million species and one billion different types of marine microbes (14). Today, around 28,000 new compounds isolated from marine species, such as algae, seaweed, sponges, and starfish, have been reported, and this species diversity provides a diverse array of secondary metabolic products (15, 16). In this review, we present NPs derived from marine environments, and summari...

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“…In addition, anticancer activity of renieramycin T was evidenced with apoptosis-inducing effect [33]. Recently, the new series of hydroquinone monoester derivatives of renieramycin M have been reported as the potential cytotoxic agents against human lung cancer cells [34,35]. The hydroquinone analogues of renieramycin M such as hydroquinone 5-O-acetyl ester (4) and hydroquinone 5-O-cinnamoyl ester (5) significantly induced apoptosis by increasing expression of apoptosis-inducing factor [35,36].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the new series of hydroquinone monoester derivatives of renieramycin M have been reported as the potential cytotoxic agents against human lung cancer cells [34,35]. The hydroquinone analogues of renieramycin M such as hydroquinone 5-O-acetyl ester (4) and hydroquinone 5-O-cinnamoyl ester (5) significantly induced apoptosis by increasing expression of apoptosis-inducing factor [35,36]. Among various semi-synthetic derivatives, 22-O-amino ester derivative of renieramycin M, namely 22-O-(N-Boc-l-glycine) ester of renieramycin M (6), exhibits potent anticancer activity against human lung cancer, which was indicated with lower half-maximal inhibitory concentration (IC 50 ) compared to renieramycin M [34].…”

Section: Introductionmentioning

confidence: 99%

22-O-(N-Boc-l-glycine) ester of renieramycin M inhibits migratory activity and suppresses epithelial–mesenchymal transition in human lung cancer cells

Nealiga

Suwanborirux

et al. 2021

J Nat Med

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The incidence of metastasis stage crucially contributes to high recurrence and mortality rate in lung cancer patients. Unfortunately, no available treatment inhibits migration, a key metastasis process in lung cancer. In this study, the effect of 22-O-(N-Boc-l-glycine) ester of renieramycin M (22-Boc-Gly-RM), a semi-synthetic amino ester derivative of bistetrahydroisoquinolinequinone alkaloid isolated from Xestospongia sp., on migratory behavior of human lung cancer cells was investigated. Following 24 h of treatment, 22-Boc-Gly-RM at non-toxic concentrations (0.5-1 μM) effectively restrained motility of human lung cancer H460 cells assessed through wound healing, transwell migration, and multicellular spheroid models. The capability to invade through matrix component was also repressed in H460 cells cultured with 0.1-1 µM 22-Boc-Gly-RM. The dose-dependent reduction of phalloidin-stained actin stress fibers corresponded with the downregulated Rac1-GTP level presented via western blot analysis in 22-Boc-Gly-RM-treated cells. Treatment with 0.1-1 μM of 22-Boc-Gly-RM obviously caused suppression of p-FAK/p-Akt signal and consequent inhibition of epithelial-to-mesenchymal transition (EMT), which was evidenced with augmented level of E-cadherin and reduction of N-cadherin expression. The alteration of invasion-related proteins in 22-Boc-Gly-RM-treated H460 cells was indicated by the diminution of matrix metalloproteinases (MT1-MMP, MMP-2, MMP-7, and MMP-9), as well as the upregulation of tissue inhibitors of metalloproteinases (TIMP), TIMP2, and TIMP3. Thus, 22-Boc-Gly-RM is a promising candidate for anti-metastasis treatment in lung cancer through inhibition of migratory features associated with suppression on EMT.

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Apoptosis-inducing Effect of Hydroquinone 5-O-Cinnamoyl Ester Analog of Renieramycin M on Non-small Cell Lung Cancer Cells

Abstract: This study revealed the potential of CIN-RM for apoptosis induction and in the development of a novel anticancer agent.

Cited by 8 publications

References 26 publications

Synthesis and Biological Evaluation of Cyclic Analogues from Nitrone LQB-278: A New Potential Antileukemia Compound

Synthesis and Biological Evaluation of Cyclic Analogues from Nitrone LQB-278: A New Potential Antileukemia Compound

Therapeutic Application of Diverse Marine-derived Natural Products in Cancer Therapy

22-O-(N-Boc-l-glycine) ester of renieramycin M inhibits migratory activity and suppresses epithelial–mesenchymal transition in human lung cancer cells

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