Tetrandrine sensitizes nasopharyngeal carcinoma cells to irradiation by inducing autophagy and inhibiting MEK/ERK pathway

Wang, Jun; Yao, Zhouzhou; Lai, Xiaoping; Bao, Hongwei; Li, Yue; Li, Shuaixiang; Chang, Lihong; Zhang, Gehua

doi:10.1002/cam4.3356

Cited by 20 publications

(16 citation statements)

References 34 publications

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“…Downregulation of ERK phosphorylation can promote G2/M phase arrest of human leukemia cells through ERK inhibitors 34 . Tetrandrine increased the radiosensitivity of NPC cells (CNE‐1 and CNE‐2) by inhibiting ERK phosphorylation under the maximum non‐cytotoxic dose condition but has shown no correlation to the p38 and JNK pathways 18 . In particular, inhibition of the MEK/ERK/c‐MYC pathway inhibits the cell proliferation, migration, and invasion of NPC 18 .…”

Section: Discussionmentioning

confidence: 99%

“…For example, in several preclinical models, RAS–RAF–MEK–ERK pathway inhibitors and CDK4/6 inhibitors exerted better tumor suppressor effects when used in combination 17 . In particular, inhibition of the MEK/ERK/c‐MYC pathway can downregulate cell proliferation, migration, and invasion of NPC 18 . Previous studies have shown that lapatinib mediates an increase in the radiosensitivity of breast cancer by inhibiting the Raf/MEK/ERK mitogen‐activated protein kinase cascade reaction 19 .…”

Section: Introductionmentioning

confidence: 99%

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Cytokeratin 13 promotes radiotherapy sensitivity of nasopharyngeal carcinoma by downregulating the MEK/ERK pathway

et al. 2022

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Background: Radiation therapy is the first treatment choice for nasopharyngeal carcinoma (NPC), while radiation resistance and recurrence have become the primary factors and are associated with poor prognosis in the clinical treatment of NPC patients. The purpose of the present study was to explore the sensitivity and molecular basis of cytokeratin 13 (CK13) that regulates NPC radiotherapy.Methods: HNE-3 or C666-1 cell line was used for overexpression and knockdown tests. Under radiotherapy conditions, CCK-8 assay, clone formation assay, and flow cytometry analyzed the effects of CK13 overexpression on cell proliferation, apoptosis, and cell cycle, respectively. In addition, Western blotting detected CK13-mediated downregulation of cell cycle-related genes. The mouse subcutaneous tumor-bearing experiment identified the effects of CK13 overexpression on the treatment of NPC in vivo. Further, Western blotting, CCK-8 assay, and flow cytometry investigated whether the CK13-mediated cell apoptosis involves the MEK/ERK signaling pathway. Results: Overexpression of CK13 significantly inhibited the survival of HNE-3 cells under radiotherapy in vitro and in vivo, and there was a substantial decrease in cyclin-dependent kinase 4 and 6 (CDK4/6) levels promoting the cell percentage number in the G2/M phase and, subsequently, the ratio of the apoptotic cells. In contrast, the knockdown of CK13 showed the opposite partial regulatory effect. Interestingly, CK13 overexpression also showed a reduction in the survival of C666-1 cells and an increased ratio of the apoptotic cells under radiotherapy treatment. Furthermore, higher levels of CK13 downregulated the MEK/ERK signaling pathway, resulting in decreased HNE-3 cell proliferation and increased apoptosis. However, ERK activators were able to rescue the process partially.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytokeratin 13 promotes radiotherapy sensitivity of nasopharyngeal carcinoma by downregulating the MEK/ERK pathway

et al. 2022

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“…Tetrandrine (TET) possesses multiple pharmacological properties against a wide variety of cancers [ 163 ]. The antitumor effects of TET are associated with the induction of apoptosis and autophagy, the reversal of MDR, and the enhancement of radiation sensitization [ 163 , 164 ]. TET has been proven to be a potent broad-spectrum autophagy agonist with effects on a variety of cell lines, including triple-negative breast cancer cells, human HCC, nasopharyngeal carcinoma by inhibiting PI3K/AKT/mTOR signaling [ 164 , 165 ].…”

Section: Natural Products As Inducers Of Autophagy In Cancermentioning

confidence: 99%

“…The antitumor effects of TET are associated with the induction of apoptosis and autophagy, the reversal of MDR, and the enhancement of radiation sensitization [ 163 , 164 ]. TET has been proven to be a potent broad-spectrum autophagy agonist with effects on a variety of cell lines, including triple-negative breast cancer cells, human HCC, nasopharyngeal carcinoma by inhibiting PI3K/AKT/mTOR signaling [ 164 , 165 ]. TET inhibits human PML-RARα-positive acute promyelocytic leukemia (APL) cell proliferation and induces autophagy by activating ROS generation and Notch1 signaling [ 261 ].…”

Section: Natural Products As Inducers Of Autophagy In Cancermentioning

confidence: 99%

Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer

Al-Bari

Ito

Ahmed

et al. 2021

IJMS

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Macro-autophagy (autophagy) is a highly conserved eukaryotic intracellular process of self-digestion caused by lysosomes on demand, which is upregulated as a survival strategy upon exposure to various stressors, such as metabolic insults, cytotoxic drugs, and alcohol abuse. Paradoxically, autophagy dysfunction also contributes to cancer and aging. It is well known that regulating autophagy by targeting specific regulatory molecules in its machinery can modulate multiple disease processes. Therefore, autophagy represents a significant pharmacological target for drug development and therapeutic interventions in various diseases, including cancers. According to the framework of autophagy, the suppression or induction of autophagy can exert therapeutic properties through the promotion of cell death or cell survival, which are the two main events targeted by cancer therapies. Remarkably, natural products have attracted attention in the anticancer drug discovery field, because they are biologically friendly and have potential therapeutic effects. In this review, we summarize the up-to-date knowledge regarding natural products that can modulate autophagy in various cancers. These findings will provide a new position to exploit more natural compounds as potential novel anticancer drugs and will lead to a better understanding of molecular pathways by targeting the various autophagy stages of upcoming cancer therapeutics.

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“…In the article by Wang et al, 1 the authors would like to add two additional funding sources under funding information:…”

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confidence: 99%

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2021

Cancer Medicine

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Tetrandrine sensitizes nasopharyngeal carcinoma cells to irradiation by inducing autophagy and inhibiting MEK/ERK pathway

Cited by 20 publications

References 34 publications

Cytokeratin 13 promotes radiotherapy sensitivity of nasopharyngeal carcinoma by downregulating the MEK/ERK pathway

Cytokeratin 13 promotes radiotherapy sensitivity of nasopharyngeal carcinoma by downregulating the MEK/ERK pathway

Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer

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