A renewed concept on the MAPK signaling pathway in cancers: Polyphenols as a choice of therapeutics

Anjum, Juhaer; Mitra, Saikat; Das, Rajib; Alam, Roksana; Mojumder, Anik; Emran, Talha Bin; Islam, Fahadul; Rauf, Abdur; Hossain, Md. Jamal; Aljohani, Abdullah S.M.; Abdulmonem, Waleed Al; Alsharif, Khalaf F.; Alzahrani, Khalid J.; Khan, Haroon

doi:10.1016/j.phrs.2022.106398

Cited by 57 publications

(29 citation statements)

References 174 publications

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“…However, the specific mechanisms of FABP6 in HCC need to be further studied. MAPK3, also known as extracellular signal-regulated kinase 1 (ERK1), is a member of the MAPK signaling pathway, which participates in tumorigenesis and metastasis in multiple tumor types 30 . ERK1, together with ERK2, plays an important role in BA metabolism.…”

Section: Discussionmentioning

confidence: 99%

A bile acid-related prognostic signature in hepatocellular carcinoma

Zhang

Wan

et al. 2022

Sci Rep

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Due to the high mortality of hepatocellular carcinoma (HCC), its prognostic models are urgently needed. Bile acid (BA) metabolic disturbance participates in hepatocarcinogenesis. We aim to develop a BA-related gene signature for HCC patients. Research data of HCC were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) online databases. After least absolute shrinkage and selection operator (LASSO) regression analysis, we developed a BA-related prognostic signature in TCGA cohort based on differentially expressed prognostic BA-related genes. Then, the predictive performance of the signature was evaluated and verified in TCGA and ICGC cohort respectively. We obtained the risk score of each HCC patient according to the model. The differences of immune status and drug sensitivity were compared in patients that were stratified based on risk score. The protein and mRNA levels of the modeling genes were validated in the Human Protein Atlas database and our cell lines, respectively. In TCGA cohort, we selected 4 BA-related genes to construct the first BA-related prognostic signature. The risk signature exhibited good discrimination and predictive ability, which was verified in ICGC cohort. Patients were classified into high- and low-risk groups according to their median scores. The occurrence of death increased with increasing risk score. Low-risk patients owned favorable overall survival. High-risk patients possessed high immune checkpoint expression and low IC50 values for sorafenib, cisplatin and doxorubicin. Real-time quantitative PCR and immunohistochemical results validate expression of modeling genes in the signature. We constructed the first BA-related gene signature, which might help to identify HCC patients with poor prognosis and guide individualized treatment.

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Section: Discussionmentioning

confidence: 99%

A bile acid-related prognostic signature in hepatocellular carcinoma

Zhang

Wan

et al. 2022

Sci Rep

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“…The p38 mitogen-activated protein kinase (MAPK) signaling pathway plays a key role in regulating many cellular processes, including cell proliferation, differentiation, apoptosis, and chemoresistance, in various types of cancers, including ovarian cancer [ 89 , 90 ]. The MAPK family includes many members, but p38, extracellular signal-regulated kinase (ERK), and c-Jun NH2- terminal kinase (JNK) are considered the key players in carcinogenesis and are the most studied [ 90 , 91 ]. Interestingly, Xie and colleagues found that the expression of p-p38 MAPK was significantly increased in cisplatin-resistant SKOV3/CDDP ovarian cancer cells as well as in the primary ovarian cancer tissues.…”

Section: Role Of Metformin In Cotreatment With Sb203580 or Phenethyl ...mentioning

confidence: 99%

Metformin Improves Ovarian Cancer Sensitivity to Paclitaxel and Platinum-Based Drugs: A Review of In Vitro Findings

Tossetta

2022

IJMS

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Ovarian cancer is one of the most dangerous gynecologic cancers worldwide, showing a high fatality rate and recurrence due to diagnosis at an advanced stage of the disease and the occurrence of chemoresistance, which weakens the therapeutic effects of the chemotherapeutic treatments. In fact, although paclitaxel and platinum-based drugs (carboplatin or cisplatin) are widely used alone or in combination to treat ovarian cancer, the occurrence of chemoresistance significantly reduces the effects of these drugs. Metformin is a hypoglycemic agent that is commonly used for the treatment of type 2 diabetes mellitus and non-alcoholic fatty liver disease. However, this drug also shows anti-tumor activity, reducing cancer risk and chemoresistance. This review analyzes the current literature regarding the role of metformin in ovarian cancer and investigates what is currently known about its effects in reducing paclitaxel and platinum resistance to restore sensitivity to these drugs.

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“…A number of studies suggested that MAPKs, including JNK1/2 and ERK and their related upstream or downstream signal molecules such as MEK can regulate Nur77 expression ( Anjum et al, 2022 ). Our results showed that venlafaxine could activated the JNK/c-Jun and the MERK/ERK pathway.…”

Section: Discussionmentioning

confidence: 99%

Venlafaxine, an anti-depressant drug, induces apoptosis in MV3 human melanoma cells through JNK1/2-Nur77 signaling pathway

Niu

Wei

et al. 2023

Front. Pharmacol.

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Introduction: Venlafaxine is one of the most commonly used anti-depressant and antineoplastic drug. Previous studies have predicted venlafaxine as an anti-cancer compound, but the therapeutic effects of venlafaxine in melanoma have not yet been demonstrated. Nur77 is an orphan nuclear receptor that highly expressed in melanoma cells and can interact with Bcl-2 to convert Bcl-2 from an antiapoptotic to a pro-apoptotic protein.Method: We examined the effects of venlafaxine in MV3 cells in vitro and MV3 xenograft tumor in nude mice. Western-blot, PCR, TUNEL assay and immunofluorescence were used to reveal the growth of melanoma cells.Results: Here, our data revealed that venlafaxine could reduce the growth, and induce apoptosis of melanoma cells through a Nur77-dependent way. Our results also showed that treatment with venlafaxine (20 mg/kg, i.p.) potently inhibited the growth of melanoma cells in nude mice. Mechanistically, venlafaxine activated JNK1/2 signaling, induced Nur77 expressions and mitochondrial localization, thereby promoting apoptosis of melanoma cells. Knockdown of Nur77 and JNK1/2, or inhibition of JNK1/2 signaling with its inhibitor SP600125 attenuated the anti-cancer effects of venlafaxine.Conclusion: In summary, our results suggested venlafaxine as a potential therapy for melanoma.

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A renewed concept on the MAPK signaling pathway in cancers: Polyphenols as a choice of therapeutics

Cited by 57 publications

References 174 publications

A bile acid-related prognostic signature in hepatocellular carcinoma

A bile acid-related prognostic signature in hepatocellular carcinoma

Metformin Improves Ovarian Cancer Sensitivity to Paclitaxel and Platinum-Based Drugs: A Review of In Vitro Findings

Venlafaxine, an anti-depressant drug, induces apoptosis in MV3 human melanoma cells through JNK1/2-Nur77 signaling pathway

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