Interplay between PI3K/Akt and MAPK signaling pathways in DNA-damaging drug-induced apoptosis

MAPK (mitogen-activated protein kinase) signaling pathways regulate a variety of biological processes through multiple cellular mechanisms. In most of these processes, such as apoptosis, MAPKs have a dual role since they can act as activators or inhibitors, depending on the cell type and the stimulus. In this review, we present the main pro- and anti-apoptotic mechanisms regulated by MAPKs, as well as the crosstalk observed between some MAPKs. We also describe the basic signaling properties of MAPKs (ultrasensitivity, hysteresis, digital response), and the presence of different positive feedback loops in apoptosis. We provide a simple guide to predict MAPKs’ behavior, based on the intensity and duration of the stimulus. Finally, we consider the role of MAPKs in osmostress-induced apoptosis by using Xenopus oocytes as a cell model. As we will see, apoptosis is plagued with multiple positive feedback loops. We hope this review will help to understand how MAPK signaling pathways engage irreversible cellular decisions.

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Myricetin Protects Cells against Oxidative Stress-Induced Apoptosis via Regulation of PI3K/Akt and MAPK Signaling Pathways

International Journal of Molecular Sciences ◽

10.3390/ijms11114348 ◽

2010 ◽

Vol 11 (11) ◽

pp. 4348-4360 ◽

Cited By ~ 67

Author(s):

Kyoung Ah Kang ◽

Zhi Hong Wang ◽

Rui Zhang ◽

Mei Jing Piao ◽

Ki Cheon Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathways ◽

Mapk Signaling ◽

Induced Apoptosis ◽

Mapk Signaling Pathways

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Correction: Kang, K.A.; et al., Myricetin Protects Cells against Oxidative Stress-Induced Apoptosis via Regulation of PI3K/Akt and MAPK Signaling Pathways. Int. J. Mol. Sci. 2010, 11, 4348–4360

International Journal of Molecular Sciences ◽

10.3390/ijms16011482 ◽

2015 ◽

Vol 16 (1) ◽

pp. 1482-1483 ◽

Cited By ~ 2

Author(s):

Kyoung Kang ◽

Zhi Wang ◽

Rui Zhang ◽

Mei Piao ◽

Ki Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathways ◽

Mapk Signaling ◽

Induced Apoptosis ◽

Mapk Signaling Pathways

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Antrocin Sensitizes Prostate Cancer Cells to Radiotherapy through Inhibiting PI3K/AKT and MAPK Signaling Pathways

Cancers ◽

10.3390/cancers11010034 ◽

2018 ◽

Vol 11 (1) ◽

pp. 34 ◽

Cited By ~ 8

Author(s):

Yu-An Chen ◽

David T. W. Tzeng ◽

Yi-Ping Huang ◽

Chun-Jung Lin ◽

U-Ging Lo ◽

...

Keyword(s):

Prostate Cancer ◽

Signaling Pathways ◽

Therapeutic Potential ◽

Treatment Options ◽

Mapk Signaling ◽

Downstream Signaling ◽

Cancer Types ◽

Induced Apoptosis ◽

Mapk Signaling Pathways

Radiotherapy is one of the most common treatment options for local or regional advanced prostate cancer (PCa). Importantly, PCa is prone to radioresistance and often develops into malignancies after long-term radiotherapy. Antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, possesses pharmacological efficacy against various cancer types; however, its therapeutic potential requires comprehensive exploration, particularly in radioresistant PCa cells. In this study, we emphasized the effects of antrocin on radioresistant PCa cells and addressed the molecular mechanism underlying the radiosensitization induced by antrocin. Our results showed that a combination treatment with antrocin and ionizing radiation (IR) synergistically inhibited cell proliferation and induced apoptosis in radioresistant PCa cells. We further demonstrated that antrocin downregulated PI3K/AKT and MAPK signaling pathways as well as suppressed type 1 insulin-like growth factor 1 receptor (IGF-1R)-mediated induction of β-catenin to regulate cell cycle and apoptosis. Using xenograft mouse models, we showed that antrocin effectively enhanced radiotherapy in PCa. Our study demonstrates that antrocin sensitizes PCa to radiation through constitutive suppression of IGF-1R downstream signaling, revealing that it can be developed as a potent therapeutic agent to overcome radioresistant PCa.

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Autophagy protects bone marrow mesenchymal stem cells from palmitate‑induced apoptosis through the ROS‑JNK/p38 MAPK signaling pathways

Molecular Medicine Reports ◽

10.3892/mmr.2018.9100 ◽

2018 ◽

Cited By ~ 7

Author(s):

Yongyi Liu ◽

Ning Wang ◽

Shaokun Zhang ◽

Qingwei Liang

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Signaling Pathways ◽

P38 Mapk ◽

Mapk Signaling ◽

Marrow Mesenchymal Stem Cells ◽

Induced Apoptosis ◽

Mapk Signaling Pathways

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Ethyl Acetate Extract of Asclepias curassavica Induced Apoptosis in Human Cancer Cells via Activating p38 and JNK MAPK Signaling Pathways

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/9076269 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Xi Zheng ◽

Ying Xu ◽

Bei Liu ◽

Yan Qi ◽

Ying Zhang ◽

...

Keyword(s):

Ethyl Acetate ◽

Signaling Pathways ◽

Antitumor Effect ◽

Molecular Mechanisms ◽

Ethyl Acetate Extract ◽

Mapk Signaling ◽

Asclepias Curassavica ◽

Induced Apoptosis ◽

Mapk Signaling Pathways

Background. Asclepias curassavica L. (Asclepiadaceae), as a traditional medicinal plant, is used as treatment for tumors in traditional Chinese and Indian medical practice. However, its underlying molecular mechanisms remain largely unresolved. The current study investigated its antitumor activity and the underlying molecular mechanisms. Method. Cell viability was detected by a real-time cell analysis system and MTT assay. Antitumor effect of ethyl acetate extract of Asclepias curassavica (EAAC) on NIC-H1975 tumors in vivo was assessed in BALB/c-nu/nu mouse. Apoptosis was measured using Hoechst33342 staining and Annexin V/PI-staining. Apoptosis-related proteins and MAPK signaling pathways were analyzed based on Western blot assay. Results. EAAC exhibited the highest cytotoxic activity in vitro than other polar parts. Meanwhile, EAAC could inhibit sensitive cell line NIC-H1975 proliferation in a concentration-dependent and time-dependent manner. Furthermore, EAAC had a significant inhibitory effect on NIC-H1975 tumor growth in BALB/c-nu/nu mouse. NIC-H1975 cells showed obvious apoptosis characteristics after EAAC treatment. Fas, caspase family members caspase 3, caspase 9, and caspase 8 showed dose-dependent induction by EAAC treatment, with increasing PARP cleavage. Additionally, EAAC significantly downregulated antiapoptotic proteins Bcl-2, XIAP, survivin, and Mcl-1 and upregulated proapoptosis proteins Bak, Bax, as well as activation of p38 and JNK MAPK signaling pathways. Moreover, inhibiting p38 and JNK MAPK by pharmacological inhibitors abrogated EAAC-induced apoptosis. Conclusion. Our data indicated that EAAC exerted potent antitumor effect both in vitro and in vivo by triggering the apoptotic pathway.

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Astragaloside IV Ameliorates Myocardial Infarction Induced Apoptosis and Restores Cardiac Function

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.671255 ◽

2021 ◽

Vol 9 ◽

Author(s):

Chuang Sun ◽

Guangwei Zeng ◽

Tingting Wang ◽

He Ren ◽

Huixian An ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Signaling Pathways ◽

Signaling Pathway ◽

Cardiac Fibrosis ◽

Mapk Signaling ◽

Diabetic Mice ◽

Astragaloside Iv ◽

Induced Apoptosis ◽

Mapk Signaling Pathways

BackgroundType 2 diabetes mellitus increases the risk of cardiovascular disease including myocardial infarction (MI). Inflammation and apoptosis have been implicated in the pathophysiology of MI. In the present study, the effects of astragaloside IV (AS-IV) on MI in diabetic mice were evaluated.MethodsHigh glucose/high fat (HG/HF) and hypoxia culture condition were established to mimic diabetic condition. After administration of AS-IV to H9c2 myocytes, the cell apoptosis, viability, and activation of mitogen-activated protein kinase (MAPK) signaling pathways were detected. MI was induced in streptozotocin-induced diabetic mice. After administration of AS-IV to mice, cardiac function, cardiac fibrosis, inflammation, and activation of MAPK signaling pathway were detected.ResultsAstragaloside IV treatment significantly inhibited HG/HF and hypoxia-induced apoptosis of H9c2. AS-IV inhibited activation of JNK and p38 signaling pathway while promoting the activation of EKR signaling pathway. AS-IV treatment rescued cardiac function, suppressed cardiac fibrosis and inflammation, and differently regulated the activation of MAPK signaling pathways.ConclusionAstragaloside IV prevented apoptosis and restored cardiac function in MI, which may be due to the regulation of MAPK signaling pathway in diabetes.

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