Probucol modulates iron nitrilotriacetate (Fe-NTA)-dependent renal carcinogenesis and hyperproliferative response: diminution of oxidative stress

Iqbal, Mohammad; Okazaki, Yasumasa; Okada, Shigeru

doi:10.1007/s11010-007-9486-6

Cited by 13 publications

(7 citation statements)

References 36 publications

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“…In animals, probucol prevents intimal thickening after balloon injury, independent of its ability to lower cholesterol and inhibit lipoprotein lipid oxidation [14] . Probucol is reported to exert antitumor activities at various stages of tumor initiation, promotion and progression [15] . However, these findings do not explain the roles of probucol in AMPK activation and cell growth in glioma.…”

Section: Introductionmentioning

confidence: 99%

Probucol suppresses human glioma cell proliferation in vitro via ROS production and LKB1-AMPK activation

et al. 2014

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Aim: Probucol, an anti-hyperlipidemic drug, has been reported to exert antitumor activities at various stages of tumor initiation, promotion and progression. In this study we examined whether the drug affected glioma cell growth in vitro and the underlying mechanisms. Methods: Human glioma U87 and glioblastoma SF295 cell lines were used. Cell proliferation was accessed using the cell proliferation assay and BrdU incorporation. The phosphorylation of AMPK, liver kinase B1 (LKB1) and p27 Kip1 was detected by Western blot. The activity of 26S proteasome was assessed with an in situ fluorescent substrate. siRNAs were used to suppress the expression of the relevant signaling proteins. Results: Treatment of U87 glioma cells with probucol (10-100 μmol/L) suppressed the cell proliferation in dose-and time-dependent manners. Meanwhile, probucol markedly increased the ROS production, phosphorylation of AMPK at Thr172 and LKB1 at Ser428 in the cells. Furthermore, probucol significantly decreased 26S proteasome activity and increased p27 Kip1 protein level in the cells in an AMPK-dependent manner. Probucol-induced suppression of U87 cell proliferation could be reversed by pretreatment with tempol (a superoxide dismutase mimetic), MG132 (proteasome inhibitor) or compound C (AMPK inhibitor), or by gene silencing of LKB1, AMPK or p27 Kip1 . Similar results were observed in probucol-treated SF295 cells. Conclusion: Probucol suppresses human glioma cell proliferation in vitro via ROS production and LKB1-AMPK activation, which reduces 26S proteasome-dependent degradation of p27 Kip1 .

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Section: Introductionmentioning

confidence: 99%

Probucol suppresses human glioma cell proliferation in vitro via ROS production and LKB1-AMPK activation

et al. 2014

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“…In one of these studies, directed nanoassembly formulation of probucol was tested and it was shown to suppress lung metastasis of breast cancer 24 and in another study it inhibited benzopyrene induced lung tumorigenesis 25 .In addition, probucol was reported to induce antiproliferative effects via inhibition of cell cycle progression and inactivation of NF-κB and MAPK pathways in human ovarian cancer cells 26 . Probucol was also reported to exert chemopreventive effect in kidney cancer 27 and probucol treatment of KB cells xenografts in mice had a significant anticancer effect by anti-angiogenic and apoptosis inducing mechanisms 28 . In our knowledge, this is the first study investigating the effects of probucol on K562S, K562R chronic myeloid leukemia, U266, H929 and RPMI8226 multipl myeloma and L929 fibroblast cell lines.…”

Section: Discussionmentioning

confidence: 99%

Effects of Probucol on Cell Proliferation in Leukemia, Multiple Myeloma, Lymphoma and Fibroblast Cell Lines

Koç¹,

Karabay²,

Yaprak³

et al. 2019

tjps

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ÖZ GİRİŞ ve AMAÇ: Probukol, antiiflamatuar, antilipidemik ve antidiyabetik aktivitelere sahip bisfenol bir antioksidandır. Kanser gelişimi ve ilerlemesi kronik inflamasyon ve oksidatif stres ile yakından ilişkilidir ve bu olguları hedefleyen ajanların kanser hücre proliferasyonunu modüle ettikleri gösterilmiştir. Bu bağlamda, bu çalışmada, probukolün farklı kanser hücre serilerinin proliferasyonu üzerindeki etkileri araştırılmıştır. YÖNTEM ve GEREÇLER: Probukolün farklı konsantrasyonlarında hazırlanan çözeltileri kullanılarak K562S (Imatinib duyarılı), K562R (Imatinib dirençli) kronik miyeloid lösemi, U937 histiositik lenfoma, HL60 akut miyeloid lösemi, U266 multipl miyeloma ve L929 fibroblast hücre serilerinde hücre canlılığı MTT testi ile belirlenmiştir. BULGULAR: Probukol uygulaması (0.1µM-10 µM), K562S, K562R kronik miyeolid lösemi, U937 histositik lenfoma, HL60 akut miyeloid lösemi, U266, H929, RPMI8226 multipl miyelom ve L929 fibroblast hücre serilerinde anlamlı bir etki göstermemiştir. Diğer taraftan, probukol uygulaması, H929 ve RPMI8226 hücre serilerinin canlılığını sırasıyla 0.5-10 µM and 5-10 µM konsantrasyon aralığında anlamlı olarak azaltmıştır (p<0.05). TARTIŞMA ve SONUÇ: Probukol uygulaması H929 ve RPMI8226 multipl miyelom hücre serilerinin canlılığını anlamlı olarak inhibe etmiştir. Fakat, probukolün bu etkisi potent bulunmamıştır ve uygulanan konsantrasyon aralığında, hücre canlılığında % 50 ve üzerinde azalma sergilemediği belirlenmiştir. Anahtar Kelimeler: Probukol, kronik miyeloid lösemi, multipl miyelom, histositik lenfoma, akut miyeloid lösemi INTRODUCTION: Probucol is a bis-phenol antioxidant with antiinflammatory, antilipidemic and antidiabetic activites. Development and progression of cancer is closely linked with chronic inflammation and oxidative stress and agents target these processes have been shown to modulate cancer cell proliferation. In this regard, effects of probucol on proliferation of different cancer cell lines was investigated in this study. METHODS: Different concentrations of probucol solutions were prepared and applied to K562S (Imatinib sensitive), K562R (Imatinib resistant) chronic myeloid leukemia, U937 histiocytic lymphoma, HL60 acute myeloid leukemia, U266, H929, RPMI8226 multiple myeloma and L929 fibroblast cell lines before determining cell viability with MTT test. RESULTS: Probucol treatment (0.1 µM-10 µM) did not exhibit significant toxicity in K562S, K562R chronic myeloid leukemia, U937 histiocytic lymphoma, HL60 acute myeloid leukemia, U266 multiple myeloma and L929 fibroblast cell lines. On the other hand, probucol treatment significantly inhibited H929 and RPMI8226 multiple myeloma cell viability at 0.5-u n c o r r e c t e d p r o o f 10 µM and 5-10 µM concentration ranges respectively. DISCUSSION AND CONCLUSION: Probucol treatment inhibited cell viability slightly but significantly in H929 and RPMI8226 multiple myeloma cell lines. However, its effect was not found to be potent since 50% diminishment in cell viability could not be achieved with the applied c...

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“…Previously, it has been demonstrated that human diet contains many antimutagens and antioxidants. These compounds have been reported to play a significant role in the inhibition of the initiation and the promotion of some cancer [ 20 ]. Recently, researchers have been focused on the study of the chemoprotective and anticancer properties of a variety of antioxidants.…”

Section: Discussionmentioning

confidence: 99%

“…The obtained solution was then mixed to an H 2 O 2 , 200 mM 1 : 1 (v/v) (Fisher Scientific, USA). This oxidizing solution was used immediately after preparation [ 14 , 20 ].…”

Section: Methodsmentioning

confidence: 99%

Zanthoxylum heitzii Modulates Ferric Nitrilotriacetate‐Dependent Oxidative Alterations in Four Vital Organs: An In Vitro Organoprotective Model

Essogo

Moukette

Tankeu

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Ferric nitrilotriacetate (Fe-NTA) is a highly reactive compound used to induce degenerative disorders through oxidative stress (OS). Zanthoxylum heitzii (Z. heitzii) is a spice used as a medicinal plant to treat a variety of illnesses. This study investigated the ability of extracts from the leaves, fruits, roots, and barks of Z. Heitzii to inhibit Fe-NTA mediated oxidative damage in rats. The supernatant of rat liver homogenates was pretreated with the extracts for one hour before the induction of oxidative damage using a solution of Fe-NTA (400 mM). The activities of superoxide dismutase (SOD), catalase, and peroxidases were measured together with the marker of lipid peroxidation and the level of glutathione. The pretreated groups showed a significant increase in the activity of SOD, catalase, and peroxidases. The methanolic extract from the leaves of Z. heitzii (36.78 ± 3.30) and aqueous extract from the fruits (37.01 ± 2.52) showed the highest activities of SOD in the liver. The lowest concentration of MDA was found in the liver, and the glutathione was greater in the brain. Conclusively, these results suggest that Z. heitzii might be a chemoprotector which may be used in for prevention of distinct types of diseases induced by oxidative stress.

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Probucol modulates iron nitrilotriacetate (Fe-NTA)-dependent renal carcinogenesis and hyperproliferative response: diminution of oxidative stress

Cited by 13 publications

References 36 publications

Probucol suppresses human glioma cell proliferation in vitro via ROS production and LKB1-AMPK activation

Probucol suppresses human glioma cell proliferation in vitro via ROS production and LKB1-AMPK activation

Effects of Probucol on Cell Proliferation in Leukemia, Multiple Myeloma, Lymphoma and Fibroblast Cell Lines

Zanthoxylum heitzii Modulates Ferric Nitrilotriacetate‐Dependent Oxidative Alterations in Four Vital Organs: An In Vitro Organoprotective Model

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