Sirt3 activates autophagy to prevent DOX-induced senescence by inactivating PI3K/AKT/mTOR pathway in A549 cells

Fan, Xiaoliang; He, Yuting; Wu, Guihao; Chen, Hongce; Cheng, Xuecheng; Zhan, Yongtong; An, Chunlei; Chen, Tongsheng; Wang, Xiaoping

doi:10.1016/j.bbamcr.2022.119411

Cited by 21 publications

(9 citation statements)

References 82 publications

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“…The AKT agonist SC79 is capable of phosphorylating and activating a range of AKT subtypes such that it is widely employed in studies focused on the PI3K/AKT/mTOR signaling pathway. 50 , 51 Here, an increase in p-AKT and p-mTOR levels was noted in TOP2A-knockdown cells following SC79 treatment ( Figure 7a–c ), which rescued the proliferative ability of these OC cells and promoted the G1-S phase cell cycle transition ( Figure 7d–h ). These data further confirmed the ability of TOP2A to modulate C-myc and CyclinD1/CDK4 complex expression levels in an AKT/mTOR pathway-dependent fashion, ultimately promoting OC cell proliferation ( Figure 8a–c ).…”

Section: Discussionmentioning

confidence: 86%

TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation

Zhang,

Zheng,

Sun

et al. 2024

Cancer Biology & Therapy

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Ovarian cancer (OC) is a form of gynecological malignancy that is associated with worse patient outcomes than any other cancer of the female reproductive tract. Topoisomerase II α (TOP2A) is commonly regarded as an oncogene that is associated with malignant disease progression in a variety of cancers, its mechanistic functions in OC have yet to be firmly established. We explored the role of TOP2A in OC through online databases, clinical samples, in vitro and in vivo experiments. And initial analyses of public databases revealed high OC-related TOP2A expression in patient samples that was related to poorer prognosis. This was confirmed by clinical samples in which TOP2A expression was elevated in OC relative to healthy tissue. Kaplan-Meier analyses further suggested that higher TOP2A expression levels were correlated with worse prognosis in OC patients. In vitro, TOP2A knockdown resulted in the inhibition of OC cell proliferation, with cells entering G1 phase arrest and undergoing consequent apoptotic death. In rescue assays, TOP2A was confirmed to regulate cell proliferation and cell cycle through AKT/mTOR pathway activity. Mouse model experiments further affirmed the key role that TOP2A plays as a driver of OC cell proliferation. These data provide strong evidence supporting TOP2A as an oncogenic mediator and prognostic biomarker related to OC progression and poor outcomes. At the mechanistic level, TOP2A can control tumor cell growth via AKT/mTOR pathway modulation. These preliminary results provide a foundation for future research seeking to explore the utility of TOP2A inhibitor-based combination treatment regimens in platinum-resistant recurrent OC patients.

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Section: Discussionmentioning

confidence: 86%

TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation

Zhang,

Zheng,

Sun

et al. 2024

Cancer Biology & Therapy

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“…DOX can kill cancer cells by inducing production of ROS, and then ROS levels of A549 cells co-cultured with various samples for 24 h were evaluated. As shown in Figure C, it can be found that the ROS level of JMPs-treated cells without DOX was equivalent to that of the control group, and both of which were very low.…”

Section: Resultsmentioning

confidence: 99%

Fabrication of Red Blood Cell-Mimicking Janus Microparticles with Enhanced Upconversion Luminescence and Drug Delivery Performance Using Double-Needle Electrospray

Cui

et al. 2023

ACS Appl. Polym. Mater.

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The shape and function of micro-/nano-particles for loading drugs play an important role in the transportation process of the drug delivery system. This study successfully fabricated red blood cell (RBC)-mimicking Janus microparticles (JMPs) using doubleneedle electrospray, which contained porous Fe 3 O 4 magnetic nanoparticles (MNPs) and upconversion (UC) luminescent nanoparticles NaYF 4 :Yb 3+ ,Er 3+ and exhibited a unique two-compartment structure. The JMPs possessed excellent magnetic and UC luminescent properties, as well as good hemocompatibility and cellular compatibility. Importantly, the two compartments of the Janus structure significantly enhanced the UC luminescent intensity compared to single compartment microparticles by reducing direct interactions between Fe 3 O 4 MNPs and UC luminescent materials. By utilizing the porous structure of Fe 3 O 4 MNPs, doxorubicin hydrochloride was loaded into Fe 3 O 4 MNPs and then embedded into the JMPs resulting in a slow-release effect. Given the excellent properties of magnetic and UC luminescence, biocompatibility, and drug slow-release ability, the RBC-mimicking JMPs have significant potential for drug delivery and bioimaging applications.

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“…Conversely, in breast cancer, SIRT3-mediated autophagy via the 5'-adenosine monophosphate-activated protein kinase (AMPK)-related pathway suppresses cell proliferation, migration, and invasion 71 . SIRT3 promotes the doxorubicin (DOX)-resistance of lung cancer cells by enhancing autophagy to counteract DOX-induced senescence primarily through the inhibition of PI3K/AKT/mTOR signaling 72 . SIRT3 enhances DNA damage repair and promotes radiation resistance in colorectal cancer cells by inducing mitophagy 73 .…”

Section: Molecular Mechanisms Of Mitochondrial Sirtuins In Cancermentioning

confidence: 99%

Mitochondrial Sirtuins in Cancer: A Revisited Review from Molecular Mechanisms to Therapeutic Strategies

Shen,

Ma,

et al. 2024

Theranostics

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The sirtuin (SIRT) family is well-known as a group of deacetylase enzymes that rely on nicotinamide adenine dinucleotide (NAD + ). Among them, mitochondrial SIRTs (SIRT3, SIRT4, and SIRT5) are deacetylases located in mitochondria that regulate the acetylation levels of several key proteins to maintain mitochondrial function and redox homeostasis. Mitochondrial SIRTs are reported to have the Janus role in tumorigenesis, either tumor suppressive or oncogenic functions. Although the multi-faceted roles of mitochondrial SIRTs with tumor-type specificity in tumorigenesis, their critical functions have aroused a rising interest in discovering some small-molecule compounds, including inhibitors and activators for cancer therapy. Herein, we describe the molecular structures of mitochondrial SIRTs, focusing on elucidating their regulatory mechanisms in carcinogenesis, and further discuss the recent advances in developing their targeted small-molecule compounds for cancer therapy. Together, these findings provide a comprehensive understanding of the crucial roles of mitochondrial SIRTs in cancer and potential new therapeutic strategies.

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Sirt3 activates autophagy to prevent DOX-induced senescence by inactivating PI3K/AKT/mTOR pathway in A549 cells

Cited by 21 publications

References 82 publications

TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation

TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation

Fabrication of Red Blood Cell-Mimicking Janus Microparticles with Enhanced Upconversion Luminescence and Drug Delivery Performance Using Double-Needle Electrospray

Mitochondrial Sirtuins in Cancer: A Revisited Review from Molecular Mechanisms to Therapeutic Strategies

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