Anticancer Effect of a Novel Octahydropyrazino[2,1-a:5,4-a′]diisoquinoline Derivative and Its Synergistic Action with<i> Nigella sativa</i> in Human Gastric Cancer Cells

Czajkowska, Anna; Gornowicz, Agnieszka; Pawłowska, Natalia; Czarnomysy, Robert; Nazaruk, Jolanta; Szymanowski, Wojciech; Bielawska, Anna; Bielawski, Krzysztof

doi:10.1155/2017/9153403

Cited by 11 publications

(7 citation statements)

References 40 publications

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“…For example, combination of Curcumin had shown to enhance the growth inhibition effect of FOLFOX in colon cancer cells [53]. Combination of Nigella sativa seed oil extract with novel octahydropyrazino[2,1-a:5,4-a′]diisoquinoline derivative (OM-90) represents stronger efficacy and enhances the anticancer effect in gastric cancer patients [54]. Resveratrol, a natural cell proliferation inhibitor, works in synergy with 5-FU thus decreasing cancer cell viability and inducing apoptosis [55].…”

Section: Discussionmentioning

confidence: 99%

Antrodia cinnamomea Enhances Chemo-Sensitivity of 5-FU and Suppresses Colon Tumorigenesis and Cancer Stemness via Up-Regulation of Tumor Suppressor miR-142-3p

et al. 2019

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5-Fluorouracil (5-FU) regimen remains the backbone of the first-line agent to treat colon cancer, but often these patients develop resistance. Cancer stem cells (CSC’s) are considered as one of the key contributors in the development of drug resistance and tumor recurrence. We aimed to provide preclinical evidence for Antrodia cinnamomea (AC), as a potential in suppressing colon cancer CSC’s to overcome 5-FU drug-resistant. In-vitro assays including cell viability, colony formation, AC + 5-FU drug combination index and tumor sphere generation were applied to determine the inhibitory effect of AC. Mouse xenograft models also incorporated to evaluate in vivo effect of AC. AC treatment significantly inhibited the proliferation, colony formation and tumor sphere generation. AC also inhibited the expression of oncogenic markers (NF-κB, and C-myc), EMT/metastasis markers (vimentin and MMP3) and stemness associated markers (β-catenin, SOX-2 and Nanog). Sequential treatment of AC and 5-FU synergized and reduces colon cancer viability both in vivo and in vitro. Mechanistically, AC mediated anti-tumor effect was associated with an increased level of tumor suppressor microRNAs especially, miR142-3p. AC can be a potent synergistic adjuvant, down-regulates cancer stemness genes and enhances the antitumor ability of 5-FU by stimulating apoptosis-associated genes, suppressing inflammation and metastasis genes through miR142-3p in colon cancer.

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Section: Discussionmentioning

confidence: 99%

Antrodia cinnamomea Enhances Chemo-Sensitivity of 5-FU and Suppresses Colon Tumorigenesis and Cancer Stemness via Up-Regulation of Tumor Suppressor miR-142-3p

et al. 2019

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“…Afterwards, the cells were examined in a fluorescence microscope Nikon Eclipse Ti connected to an inverted camera Nikon Instruments Inc., Melville, NY, USA) using 100× magnification. The results were parsed with NIS-Elements software (Nikon Instruments Inc., Melville, NY, USA) [ 52 ].…”

Section: Methodsmentioning

confidence: 99%

The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells

et al. 2021

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Cancer therapy is one of the most important challenges of modern medical and chemical sciences. Among the many methods of combating cancer, chemotherapy plays a special role. Imperfect modern chemotherapy justifies continuing the search for new, more effective, and safe drugs. Sulfonamides are the classic group of chemotherapeutic drugs with a broad spectrum of pharmacological activity. Recent literature reports show that sulfonamide derivatives have anti-tumor activity in vitro and in vivo. The aim of the study was to synthesize a novel 1,2,4-triazine sulfonamide derivative and check its anticancer potential in DLD-1 and HT-29 colon cancer cells. The biological studies included MTT assay, DNA biosynthesis, cell cycle analysis, Annexin V binding assay, ethidium bromide/acridine orange staining, and caspase-8, -9, and -3/7 activity. The concentrations of important molecules (sICAM-1, mTOR, Beclin-1, cathepsin B) involved in the pathogenesis and poor prognosis of colorectal cancer were also evaluated by ELISA. We demonstrated that the novel compound was able to induce apoptosis through intrinsic and extrinsic pathways and was capable of decreasing sICAM-1, mTOR, cathepsin B concentrations, whereas increased Beclin-1 concentration was detected in both colon cancer cell lines. The novel compound represents promising multi-targeted potential in colorectal cancer, but further in vivo examinations are needed to confirm the claim.

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“…The results were parsed with NIS-Elements software (ver. 3.00, Nikon Instruments Inc., Melville, NY, USA) [47].…”

Section: Acridine Orange/ethidium Bromide Fluorescent Stainingmentioning

confidence: 99%

The Effect of Novel 7-methyl-5-phenyl-pyrazolo[4,3-e]tetrazolo[4,5-b][1,2,4]triazine Sulfonamide Derivatives on Apoptosis and Autophagy in DLD-1 and HT-29 Colon Cancer Cells

Gornowicz

Szymanowska

Bielawski

et al. 2020

IJMS

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The discovery of cytotoxic drugs is focused on designing a compound structure that directly affects cancer cells without an impact on normal cells. The mechanism of anticancer activity is mainly related with activation of apoptosis. However, recent scientific reports show that autophagy also plays a crucial role in cancer cell progression. Thus, the objective of this study was to synthesize 7-methyl-5-phenyl-pyrazolo[4,3-e]tetrazolo[4,5-b][1,2,4]triazine utilizing nucleophilic substitution reaction at the position N1. The biological activity of tested compounds was assessed in DLD-1 and HT-29 cell lines. The induction of apoptosis was confirmed by Annexin V binding assay and acridine orange/ethidium bromide staining. The loss of mitochondrial membrane potential and caspase-8 activity was estimated using cytometer flow analysis. The concentration of p53, LC3A, LC3B and beclin-1 was measured using the ELISA technique. Our study revealed that anticancer activity of 7-methyl-5-phenyl-pyrazolo[4,3-e]tetrazolo[4,5-b][1,2,4]triazine derivatives is related with initiation of apoptosis occur on the intrinsic pathway with mitochondrial membrane decrease and extrinsic with increase of activity of caspase-8. Moreover, a decrease in beclin-1, LC3A, and LC3B were observed in two cell lines after treatment with novel compounds. This study showed that novel 7-methyl-5-phenyl-pyrazolo[4,3-e]tetrazolo[4,5-b][1,2,4]triazine derivatives might be a potential strategy in colon cancer treatment.

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Anticancer Effect of a Novel Octahydropyrazino[2,1-a:5,4-a′]diisoquinoline Derivative and Its Synergistic Action with Nigella sativa in Human Gastric Cancer Cells

Cited by 11 publications

References 40 publications

Antrodia cinnamomea Enhances Chemo-Sensitivity of 5-FU and Suppresses Colon Tumorigenesis and Cancer Stemness via Up-Regulation of Tumor Suppressor miR-142-3p

Antrodia cinnamomea Enhances Chemo-Sensitivity of 5-FU and Suppresses Colon Tumorigenesis and Cancer Stemness via Up-Regulation of Tumor Suppressor miR-142-3p

The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells

The Effect of Novel 7-methyl-5-phenyl-pyrazolo[4,3-e]tetrazolo[4,5-b][1,2,4]triazine Sulfonamide Derivatives on Apoptosis and Autophagy in DLD-1 and HT-29 Colon Cancer Cells

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