Hepatotoxic effect of tramadol and O-desmethyltramadol in HepG2 cells and potential role of PI3K/AKT/mTOR

Helmy, Manar; Abdalla, Hussein Abdelaziz; Rahman, Heba Allah Abd El; Ahmed, Dalia

doi:10.1080/00498254.2021.1961919

Cited by 8 publications

(1 citation statement)

References 71 publications

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“…Beclin1 expression tends to increase during autophagy [15,16] . Some studies have indicated that autophagy participated in the proliferation and apoptosis of cancer cells [16,17] . Our study con rmed that OXY (0.25, 0.5 and 1 mM) induced the autophagy of SKBR3 cells by upregulating the levels of autophagy related proteins LC3-and Beclin1 and further promoted the autophagy inducing ability of PTX.…”

Section: Discussionmentioning

confidence: 99%

European Journal of Medical Research Oxycodone enhances antitumor effect of paclitaxel on human breast cancer SKBR3 cells in vitro

Liu

Yuan

et al. 2022

Preprint

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Background Increasing evidence has indicated that oxycodone (OXY) can promote or prevent tumor growth and metastasis. However, the influences of OXY combined with paclitaxel (PTX) on the breast cancer cells are unclear. Our study aimed to examine the effects of OXY combined with PTX on the proliferation, apoptosis and migration of human breast cancer SKBR3 cells and the underlying mechanism was explored. Methods SKBR3 cells were treated with OXY and/or PTX. The proliferation, apoptosis and invasion of SKBR3 cells were assessed by CCK-8, colony formation assay, flowcytometric, Transwell assay and scratch assays, respectively. In addition, Western blotting was used to detect the expression of related proteins in these cells. The autophagic bodies were observed under a transmission electron microscope. Results OXY (0.25, 0.5 and 1 mM) significantly inhibited the viability, colony-forming, migration and invasion of SKBR3 cells as compared to control group. Furthermore, OXY (0.25, 0.5 and 1 mM) markedly induced the apoptosis of SKBR3 cells and the levels of apoptosis-related proteins. In addition, OXY (0.25, 0.5 and 1 mM) and PTX inhibited the proliferation of SKBR3 cells synergistically as compared to PTX group in vitro. Moreover, OXY (0.25, 0.5 and 1 mM) significantly elevated the PTX-induced apoptosis in SKBR3 cells via downregulating the expression of N-cadherin, Becline-1 LC3-Ⅱ, p-Akt and p-mTOR and upregulating E-cadherin expression. Compared with control group, OXY (1 mM) treatment induced autophagy in SKBR3 cells. OXY (1 mM) combined with PTX increased the number and size of autophagy bodies as compared to the PTX group. Moreover, OXY distinguished enhanced antitumor effect of PTX on SKBR3 cells. Conclusions Our study indicates that OXY can enhance antitumor effect of PTX on breast cancer in vitro. Hence, the combination of OXY with PTX may serve as a potential strategy for the treatment of breast cancer.

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Section: Discussionmentioning

confidence: 99%

European Journal of Medical Research Oxycodone enhances antitumor effect of paclitaxel on human breast cancer SKBR3 cells in vitro

Liu

Yuan

et al. 2022

Preprint

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Bioenergetics disruption, oxidative stress, and inflammation as underlying mechanisms of tramadol‐induced nephrotoxicity

Elmorsy,

Al Doghaither,

Al‐Ghafari

2024

J Biochem & Molecular Tox

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Tramadol (TR), a commonly prescribed pain reliever for moderate to severe pain, has been associated with kidney damage. This study investigates TR‐induced nephrotoxicity mechanisms, focusing on its effects on renal proximal tubular cells (PTCs). The study findings demonstrate that TR disrupts PTC bioenergetic processes, leading to oxidative stress and inflammation. Significant toxicity to PTCs was observed with estimated effective concentration 50 values of 9.8 and 11.5 µM based on 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and lactate dehydrogenase assays, respectively. TR also interferes with the function of PTC transporters, including organic cation uptake transporter 1, organic cation transporter 2, P‐glycoprotein, and multidrug resistance protein 2. Furthermore, bioenergetics assays showed that TR reduced the activities of mitochondrial complexes I and III, adenosine triphosphate production, mitochondrial membrane potential, and oxygen consumption rate while increasing lactate release. TR also increased the production of reactive oxygen species, lipid peroxidation thiobarbituric acid reactive substances end products, and the expression of the NRf2 gene while decreasing reduced glutathione (GSH‐R) stores and catalase and superoxide dismutase antioxidant activities. Additionally, TR increased the production of inflammatory cytokines (TNF‐α and IL‐6) and their coding genes expression. Interestingly, the study found that antioxidants like GSH‐R, inhibitors of IL‐6 and TNF‐α, and mitochondrial activating Co‐Q10 could protect cells against TR‐induced cytotoxicity. The study suggests that TR causes nephrotoxicity by disrupting bioenergetic processes, causing oxidative stress and inflammation, but antioxidants and agents targeting mitochondria may have protective and curative potential.

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Oxycodone enhances antitumor effect of paclitaxel on human breast cancer SKBR3 cells in vitro

Liu,

Yuan,

et al. 2024

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Hepatotoxic effect of tramadol and O-desmethyltramadol in HepG2 cells and potential role of PI3K/AKT/mTOR

Cited by 8 publications

References 71 publications

European Journal of Medical Research Oxycodone enhances antitumor effect of paclitaxel on human breast cancer SKBR3 cells in vitro

European Journal of Medical Research Oxycodone enhances antitumor effect of paclitaxel on human breast cancer SKBR3 cells in vitro

Bioenergetics disruption, oxidative stress, and inflammation as underlying mechanisms of tramadol‐induced nephrotoxicity

Oxycodone enhances antitumor effect of paclitaxel on human breast cancer SKBR3 cells in vitro

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