Ameliorative effect of fluvoxamine against colon carcinogenesis via COX-2 blockade with oxidative and metabolic stress reduction at the cellular, molecular and metabolic levels

Kumar, Pranesh; Kumar, Mohit; Gautam, Anurag; Sonkar, Archana Bharti; Verma, Abhishek; Singh, Amita; Nisha, Raquibun; Kumar, Dinesh; Kumar, Deepak; Mahata, Tarun; Bhattacharya, Bolay; Maity, Biswanath; Pandeya, Abhishek; Gosipatala, Sunil Babu; Saha, Sudipta

doi:10.1016/j.bbadva.2022.100046

Cited by 8 publications

(3 citation statements)

References 57 publications

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“…Besides, colorectal polyp formation was reported to increase in case of elevated serum levels of TG and TC [33]. In agreement with the previous studies, we found dyslipidemia signs including remarkably increased serum levels of TG, TC, LDL, and decreased levels of HDL in mice treated with DMH [34]. Lipid profile imbalance improved noticeably by the SMN-containing diet along with the CAPIRI combination therapy signifying the protective effect of SMN while added to the monotherapy and combination chemotherapy regimens of CAP and IRI which may be related to the decreased number of colorectal polyps in SMN-CAPIRI group that was comparable with the control group.…”

Section: Discussionsupporting

confidence: 92%

Chemotherapeutic Activity of Dietary Supplementation of Silymarin Combined with Capecitabine and Irinotecan in 1,2 Dimethylhydrazine-Induced Mouse Colon Carcinogenesis

Hassani,

Malekinejad,

Khadem-Ansari

et al. 2024

Preprint

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The flavonoid silymarin (SMN) has been widely used in preclinical and clinical studies to treat various types of cancer, either alone or in combination with chemotherapy agents. Herein, we investigated the therapeutic efficacy of SMN and its combination with capecitabine (CAP) and irinotecan (IRI) in a mouse model of colon cancer. A modified diet supplemented with SMN (2500 ppm) with mono- and combined therapy of CAP and IRI were used following 1, 2 dimethylhydrazine (DMH)-induced colon cancer. The lipid profile, liver function tests, and cytokine levels were measured. Additionally, the lipid peroxidation and inflammation indices as well as the antioxidant activities were examined. Eventually, western blotting analysis for colonic BAX and Bcl-2 levels and histopathological examination of colon sections were carried out. SMN alone and in combination with the chemotherapeutic agents could attenuate the DMH-induced hyperlipidemia and elevated liver function enzyme levels. SMN supplementation with chemotherapy agents could also improve antioxidant activity and reverse the elevated levels of lipid peroxidation and inflammatory markers. Furthermore, significant upregulation of BAX and downregulation of Bcl-2 were observed. Besides, carcinogen-induced polyp multiplicity, dysplastic, and inflammatory changes were ameliorated considerably by treatment regimens. Our results showed that the potential anticancer properties of SMN could enhance the therapeutic effects of chemotherapy agents and reduce hepatotoxicity.

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Section: Discussionsupporting

confidence: 92%

Chemotherapeutic Activity of Dietary Supplementation of Silymarin Combined with Capecitabine and Irinotecan in 1,2 Dimethylhydrazine-Induced Mouse Colon Carcinogenesis

Hassani,

Malekinejad,

Khadem-Ansari

et al. 2024

Preprint

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“…Similar study conduted by keshari et al, showed cytotoxic potential of the thiazolo[3,2-a]pyrimidine analogues against Hep-G2 cell line. In addition, a molecular docking study showed a good binding affinity and better stability with IL-6, Cyt-C, caspase-9 and caspase-3 [27][28][29][30][31] as well as hydrogen bondings with both compounds. Moreover, 9B and 12B compounds have the strong binding affinity with the caspase 9 (-7.5 kcal/mol and − 7.3 kcal/mol) and caspase 3 (-7.4 kcal/mol and − 7.2 kcal/mol) respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Biochemical parameters such as protein carbonyl (PC), superoxide dismutase (SOD), glutathione (GSH), and thiobarbituric acid reactive substances (TBARs) were estimated in 10% lung tissue homogenate using our previously standardized laboratory protocols [17,28,29].…”

Section: Measurement Of the Oxidative Changesmentioning

confidence: 99%

Antiproliferative effect of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues on IL-6 mediated STAT3 and role of the apoptotic pathway in albino Wistar rats of ethyl carbamate-induced lung carcinoma: In-silico, In-vitro, and In-vivo study

Sonkar,

Verma,

Yadav

et al. 2024

Cancer Cell Int

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Lung cancer (LC) ranks second most prevalent cancer in females after breast cancer and second in males after prostate cancer. Based on the GLOBOCAN 2020 report, India represented 5.9% of LC cases and 8.1% of deaths caused by the disease. Several clinical studies have shown that LC occurs because of biological and morphological abnormalities and the involvement of altered level of antioxidants, cytokines, and apoptotic markers. In the present study, we explored the antiproliferative activity of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues against LC using in-vitro, in-silico, and in-vivo models. In-vitro screening against A549 cells revealed compounds 9B (8-methoxy-5-(3,4,5-trimethoxyphenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) and 12B (5-(4-chlorophenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) as potential pyrimidine analogues against LC. Compounds 9B and 12B were docked with different molecular targets IL-6, Cyt-C, Caspase9, and Caspase3 using AutoDock Vina 4.1 to evaluate the binding affinity. Subsequently, in-vivo studies were conducted in albino Wistar rats through ethyl-carbamate (EC)- induced LC. 9B and 12B imparted significant effects on physiological (weight variation), and biochemical (anti-oxidant [TBAR’s, SOD, ProC, and GSH), lipid (TC, TG, LDL, VLDL, and HDL)], and cytokine (IL-2, IL-6, IL-10, and IL-1β) markers in EC-induced LC in albino Wistar rats. Morphological examination (SEM and H&E) and western blotting (IL-6, STAT3, Cyt-C, BAX, Bcl-2, Caspase3, and caspase9) showed that compounds 9B and 12B had antiproliferative effects. Accordingly, from the in-vitro, in-silico, and in-vivo experimental findings, we concluded that 9B and 12B have significant antiproliferative potential and are potential candidates for further evaluation to meet the requirements of investigation of new drug application.

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DNA cleaver with improved phosphatase and cytotoxic activity of a series of N₂O‐based zinc(II) complexes

Mukherjee,

Sarkar,

Bakibillah

et al. 2024

Applied Organom Chemis

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Three new Zn(II) Schiff base complexes, [ZnLCl2] (1), [ZnLBr2] (2) and [ZnL(SCN)2] (3), have been synthesized by adding Zn(II) salts of chloride and bromide to a compartmental ligand with NNO donor prepared through the simple condensation of pyridine‐2‐carboxaldehyde and a substituted aniline. The complexes have been identified using standard physicochemical methods, and their solid‐state structures have been determined through single‐crystal X‐ray analysis. The phosphatase‐like activity of all three complexes has been investigated using 4‐NPP as the model substrate in a DMSO/water medium. Complex 1 exhibits the highest level of phosphatase activity. The reactivity trend shows that complex 1 > complex 2 > complex 3. A plausible mechanism and the causes underlying the activity trend have been explored through DFT study, ESI‐mass spectra and 31P experiments. Complex 1 shows promising potential for use in gene‐targeted therapeutics due to its remarkable performance in DNA digestion. The excellent DNA cleavage result of complex 1 has led to the investigation of its molecular docking interaction with the liver cancer 2 receptor to study its anti‐liver cancer activity. Furthermore, in vitro anticancer activity of complex 1 also shows excellent antiproliferative activity against hepatocellular carcinoma.

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Ameliorative effect of fluvoxamine against colon carcinogenesis via COX-2 blockade with oxidative and metabolic stress reduction at the cellular, molecular and metabolic levels

Cited by 8 publications

References 57 publications

Chemotherapeutic Activity of Dietary Supplementation of Silymarin Combined with Capecitabine and Irinotecan in 1,2 Dimethylhydrazine-Induced Mouse Colon Carcinogenesis

Chemotherapeutic Activity of Dietary Supplementation of Silymarin Combined with Capecitabine and Irinotecan in 1,2 Dimethylhydrazine-Induced Mouse Colon Carcinogenesis

Antiproliferative effect of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues on IL-6 mediated STAT3 and role of the apoptotic pathway in albino Wistar rats of ethyl carbamate-induced lung carcinoma: In-silico, In-vitro, and In-vivo study

DNA cleaver with improved phosphatase and cytotoxic activity of a series of N₂O‐based zinc(II) complexes

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Ameliorative effect of fluvoxamine against colon carcinogenesis via COX-2 blockade with oxidative and metabolic stress reduction at the cellular, molecular and metabolic levels

Cited by 8 publications

References 57 publications

Chemotherapeutic Activity of Dietary Supplementation of Silymarin Combined with Capecitabine and Irinotecan in 1,2 Dimethylhydrazine-Induced Mouse Colon Carcinogenesis

Chemotherapeutic Activity of Dietary Supplementation of Silymarin Combined with Capecitabine and Irinotecan in 1,2 Dimethylhydrazine-Induced Mouse Colon Carcinogenesis

Antiproliferative effect of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues on IL-6 mediated STAT3 and role of the apoptotic pathway in albino Wistar rats of ethyl carbamate-induced lung carcinoma: In-silico, In-vitro, and In-vivo study

DNA cleaver with improved phosphatase and cytotoxic activity of a series of N2O‐based zinc(II) complexes

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DNA cleaver with improved phosphatase and cytotoxic activity of a series of N₂O‐based zinc(II) complexes