AMPK‐mTOR‐ULK1 axis activation‐dependent autophagy promotes hydroxycamptothecin‐induced apoptosis in human bladder cancer cells

Wang, Feifan; Cao, Min; Fan, Mengjing; Wu, Huitao; Huang, Wei-Ching; Zhang, Yan; Hu, Zhenghui; Jin, Xiaodong

doi:10.1002/jcp.29307

Cited by 26 publications

(21 citation statements)

References 56 publications

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“…As noted herein, ULK1 plays an important role in the initiation of autophagy [206]. The induction of protective autophagy to inhibit apoptosis is one of the reasons for the development of drug resistance in tumor cells during therapy [207].…”

Section: Small Molecule Drugs Targeting Ulk Reverse Tumor Resistancementioning

confidence: 92%

A Review of ULK1-Mediated Autophagy in Drug Resistance of Cancer

Liu

Liao

et al. 2020

Cancers

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The difficulty of early diagnosis and the development of drug resistance are two major barriers to the successful treatment of cancer. Autophagy plays a crucial role in several cellular functions, and its dysregulation is associated with both tumorigenesis and drug resistance. Unc-51-like kinase 1 (ULK1) is a serine/threonine kinase that participates in the initiation of autophagy. Many studies have indicated that compounds that directly or indirectly target ULK1 could be used for tumor therapy. However, reports of the therapeutic effects of these compounds have come to conflicting conclusions. In this work, we reviewed recent studies related to the effects of ULK1 on the regulation of autophagy and the development of drug resistance in cancers, with the aim of clarifying the mechanistic underpinnings of this therapeutic target.

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Section: Small Molecule Drugs Targeting Ulk Reverse Tumor Resistancementioning

confidence: 92%

A Review of ULK1-Mediated Autophagy in Drug Resistance of Cancer

Liu

Liao

et al. 2020

Cancers

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“…MiR-139-5p targets Bmi-1 which induces reversion of invasion and migration [ 76 ]. Hydroxycamptothecinals initiated apoptosis via promoting AMPK/mTOR pathway dependent apoptosis [ 77 ], but the exact involvement of miRNAs in this process is not yet known.…”

Section: Mirna-mediated Regulation Of Mtor In Bladder Cancermentioning

confidence: 99%

Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer

et al. 2020

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Bladder cancer (BC) is a leading cause of death among urothelial malignancies that more commonly affect male population. Poor prognosis and resistance to chemotherapy are the two most important characteristics of this disease. PI3K/Akt/mTOR signaling pathway has been considered pivotal in the regulation of proliferation, migration, invasiveness, and metastasis. Deregulation of PI3K/Akt/mTOR signaling has been found in 40% of bladder cancers. Several microRNAs (miRNAs) have been reported to interact with the PI3K/Akt/mTOR signaling pathway with a different possible role in proliferation and apoptosis in bladder cancer. Thus, miRNAs can be used as potential biomarkers for BC. Natural compounds have been in the spotlight for the past decade due to their effective anti-proliferative capabilities. However, little is known of its possible effects in bladder cancer. The aim of this review is to discuss the interplay between PI3K/Akt/mTOR, miRNAs, and natural compounds and emphasize the importance of miRNAs as biomarkers and resveratrol, curcumin and paclitaxel as a possible therapeutic approach against bladder cancer.

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“…On the other hand, activation of AMPK can also negatively interfere with cancer cells either by arresting cell growth or by priming cancer cells to be more sensitive to death signals 53 . This latter effect is usually linked to an AMPK-dependent inhibition of mTOR 53,54 , which is involved in another survival pathway within many cells 54 . However, in the current work, we found that the mTOR pathway is also activated upon treatment with SA or ASA.…”

Section: Discussionmentioning

confidence: 99%

Acetylsalicylic acid and salicylic acid present anticancer properties against melanoma by promoting nitric oxide-dependent endoplasmic reticulum stress and apoptosis

Ausina

Branco

Demaria

et al. 2020

Sci Rep

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Melanoma is the most aggressive and fatal type of skin cancer due to being highly proliferative. Acetylsalicylic acid (ASA; Aspirin) and salicylic acid (SA) are ancient drugs with multiple applications in medicine. Here, we showed that ASA and SA present anticancer effects against a murine model of implanted melanoma. These effects were also validated in 3D- and 2D-cultured melanoma B16F10 cells, where the drugs promoted pro-apoptotic effects. In both in vivo and in vitro models, SA and ASA triggered endoplasmic reticulum (ER) stress, which culminates with the upregulation of the pro-apoptotic transcription factor C/EBP homologous protein (CHOP). These effects are initiated by ASA/SA-triggered Akt/mTOR/AMPK-dependent activation of nitric oxide synthase 3 (eNOS), which increases nitric oxide and reactive oxygen species production inducing ER stress response. In the end, we propose that ASA and SA instigate anticancer effects by a novel mechanism, the activation of ER stress.

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AMPK‐mTOR‐ULK1 axis activation‐dependent autophagy promotes hydroxycamptothecin‐induced apoptosis in human bladder cancer cells

Cited by 26 publications

References 56 publications

A Review of ULK1-Mediated Autophagy in Drug Resistance of Cancer

A Review of ULK1-Mediated Autophagy in Drug Resistance of Cancer

Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer

Acetylsalicylic acid and salicylic acid present anticancer properties against melanoma by promoting nitric oxide-dependent endoplasmic reticulum stress and apoptosis

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