The role of Her2-Nrf2 axis in induction of oxaliplatin resistance in colon cancer cells

Tazehkand, Abbas Pirpour; Akbarzadeh, Maryam; Velaie, Kobra; Sadeghi, Mohammad Reza; Samadi, Nasser

doi:10.1016/j.biopha.2018.04.105

Cited by 42 publications

(13 citation statements)

References 51 publications

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“…The increase of antioxidant response by Nrf2 is also involved in chemoresistance of colon cancer cells, where the inhibition of either Nrf2 or Her2, alone and in combination, caused a significant increase in oxaliplatin-induced cytotoxicity and apoptosis with a maximum effect in SW480/Res cells having low Her2 and Nrf2 expression levels [39].…”

Section: Oxidative Stress and Chemoresistancementioning

confidence: 99%

Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

et al. 2021

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Chemoresistance represents the main obstacle to cancer treatment with both conventional and targeted therapy. Beyond specific molecular alterations, which can lead to targeted therapy, metabolic remodeling, including the control of redox status, plays an important role in cancer cell survival following therapy. Although cancer cells generally have a high basal reactive oxygen species (ROS) level, which makes them more susceptible than normal cells to a further increase of ROS, chemoresistant cancer cells become highly adapted to intrinsic or drug-induced oxidative stress by upregulating their antioxidant systems. The antioxidant response is principally mediated by the transcription factor Nrf2, which has been considered the master regulator of antioxidant and cytoprotective genes. Nrf2 expression is often increased in several types of chemoresistant cancer cells, and its expression is mediated by diverse mechanisms. In addition to Nrf2, other transcription factors and transcriptional coactivators can participate to maintain the high antioxidant levels in chemo and radio-resistant cancer cells. The control of expression and function of these molecules has been recently deepened to identify which of these could be used as a new therapeutic target in the treatment of tumors resistant to conventional therapy. In this review, we report the more recent advances in the study of Nrf2 regulation in chemoresistant cancers and the role played by other transcription factors and transcriptional coactivators in the control of antioxidant responses in chemoresistant cancer cells.

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Section: Oxidative Stress and Chemoresistancementioning

confidence: 99%

Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

et al. 2021

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“…SOD3 is also highly expressed in the mouse model of oxaliplatin-induced liver injury [89]. Oxaliplatin-resistant colon cancer cells have increased Nrf2 expression and exhibit chemotherapeutic effects via inhibition of Nrf2 signaling [90,91].…”

Section: Redox Homeostasis In Tumorigenesismentioning

confidence: 99%

Redox-Mediated Mechanism of Chemoresistance in Cancer Cells

et al. 2019

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Cellular reactive oxygen species (ROS) status is stabilized by a balance of ROS generation and elimination called redox homeostasis. ROS is increased by activation of endoplasmic reticulum stress, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family members and adenosine triphosphate (ATP) synthesis of mitochondria. Increased ROS is detoxified by superoxide dismutase, catalase, and peroxiredoxins. ROS has a role as a secondary messenger in signal transduction. Cancer cells induce fluctuations of redox homeostasis by variation of ROS regulated machinery, leading to increased tumorigenesis and chemoresistance. Redox-mediated mechanisms of chemoresistance include endoplasmic reticulum stress-mediated autophagy, increased cell cycle progression, and increased conversion to metastasis or cancer stem-like cells. This review discusses changes of the redox state in tumorigenesis and redox-mediated mechanisms involved in tolerance to chemotherapeutic drugs in cancer.

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“…As a reported OCT2 substrate, L-OHP has effective improvement on outcome of stage III COAD patients 5. In addition, recent studies found L-OHP-resistant cells in different colon cancer cells 6. However, many COAD patients have been shown to be resistant to L-OHP exposure, limiting its application in chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

<p>SMYD2-OE promotes oxaliplatin resistance in colon cancer through MDR1/P-glycoprotein via MEK/ERK/AP1 pathway</p>

Ren

Wang²,

Chen

et al. 2019

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Background: SET and MYND domain-containing protein 2 (SMYD2-OE) plays an important role in cancer development through methylating histone and non-histone proteins. However, little is known about the relevance of SMYD2-OE in colon cancer. Moreover, oxaliplatin (L-OHP) is applied as first line for colon cancer chemotherapy, but drug resistance restricts its efficacy. Unexpectedly, the mechanism of L-OHP resistance in colon cancer remains unclear. In this study, we investigated the relationship of SMYD2-OE expression and L-OHP resistance in colon cancer and further explored the underlying mechanism linking SMYD2-OE, L-OHP resistance, and colon cancer. Materials and methods: Expression levels of SMYD2-OE in colon cancer tissues of patients were tested. In vitro and in vivo assays were conducted to explore the function and mechanism of SMYD2-OE in colon cancer sensitivity to L-OHP. Results: SMYD2-OE was overexpressed in colon cancer tissues compared with non-neoplastic tissues and associated with poor prognosis of patients with colon cancer after L-OHP-based chemotherapy. Knockdown of SMYD2-OE increased colon cancer sensitivity to L-OHP in vitro and in vivo. However, SMYD2-OE overexpression promoted L-OHP resistance in colon cancer cell in vitro. In addition, SMYD2-OE could upregulate MDR1/P-glycoprotein expression depending on MEK/ERK/AP-1 signaling pathway activity. Conclusion: These results imply that SMYD2-OE promotes L-OHP resistance in colon cancer by regulating MDR1/P-glycoprotein through MEK/ERK/AP-1 signaling pathway, providing a potential strategy to sensitize che-motherapy by SMYD2-OE knockdown in colon cancer treatment.

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The role of Her2-Nrf2 axis in induction of oxaliplatin resistance in colon cancer cells

Cited by 42 publications

References 51 publications

Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

Redox-Mediated Mechanism of Chemoresistance in Cancer Cells

<p>SMYD2-OE promotes oxaliplatin resistance in colon cancer through MDR1/P-glycoprotein via MEK/ERK/AP1 pathway</p>

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