Induction of apoptosis and autophagy via sirtuin1- and PI3K/Akt/mTOR-mediated pathways by plumbagin in human prostate cancer cells

Drug Design Development and Therapy, Journal Year: 2015, Volume and Issue: unknown, P. 1511 - 1511

Published: March 1, 2015

Abstract: Plumbagin (PLB) has been shown to have anticancer activities in animal models, but the role of PLB prostate cancer treatment is unclear. This study aimed investigate effects on apoptosis and autophagy underlying mechanisms human cell lines PC-3 DU145. Our that had potent pro-apoptotic pro-autophagic DU145 cells. induced mitochondria-mediated concentration- time-dependent manners both inhibition phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target rapamycin (mTOR) p38 mitogen-activated protein (MAPK) pathways activation 5'-AMP-dependent (AMPK) as indicated by their altered phosphorylation, contributing activity PLB. Modulation basal PLB-induced lines. Furthermore, downregulated sirtuin 1 (Sirt1), Sirt1 enhanced autophagy, whereas induction abolished In addition, pre-B colony-enhancing factor/visfatin, factor/visfatin significantly Moreover, reduction intracellular reactive oxygen species (ROS) level attenuated apoptosis- autophagy-inducing These findings indicate promotes cells via Sirt1- PI3K/Akt/mTOR-mediated with contribution from AMPK-, MAPK-, visfatin-, ROS-associated pathways. Keywords: AMPK, visfatin, PC-3, DU145, ROS

Language: Английский

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Tumor Dormancy and Interplay with Hypoxic Tumor Microenvironment

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(17), P. 4305 - 4305

Published: Sept. 3, 2019

The tumor microenvironment is a key factor in disease progression, local resistance, immune-escaping, and metastasis. rapid proliferation of cells the aberrant structure blood vessels within tumors result marked heterogeneity perfusion tissue with regions hypoxia. Although most die these hypoxic conditions, part them can adapt survive for many days or months dormant state. Dormant are characterized by cell cycle arrest G0/G1 phase as well low metabolism, refractive to common chemotherapy, giving rise Despite features, retain their ability proliferate when conditions improve. An understanding regulatory machinery dormancy essential identifying early cancer biomarkers could provide rationale development novel agents target populations. In this review, we examine current knowledge mechanisms allowing discuss crucial role process.

Language: Английский

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Protective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in rats

BMC Nephrology, Journal Year: 2017, Volume and Issue: 18(1)

Published: June 15, 2017

Cisplatin (CP) is commonly used in the treatment of different types cancer but nephrotoxicity has been a major limiting factor. Therefore, present study aimed to possible protective effect rutin against induced by cisplatin rats. Forty male Wistar albino rats were randomly divided into 4 groups. Rats group 1 control intraperitoneal (i.p.) received 2.5 ml/kg, 2 CP single dose 5 mg/kg i.p. 3 orally 30 (CP plus rutin) and as 3. Kidneys harvested for histopathology gene expression c-Jun N-terminal kinases (JNK), Mitogen-activated protein kinase (MKK4), MKK7, P38 mitogen-activated (P38), tumor necrosis factors alpha (TNF-α), TNF Receptor-Associated Factor (TRAF2), interleukin-1 (IL-1-α). The administration associated with significant increase blood urea nitrogen (BUN) serum creatinine significantly Malondialdehyde (MDA) kidney tissues 230 ± 5.5 nmol/g compared group. animal treated showed levels IL-1α (260%), TRFA2 (491%), (410%), MKK4 (263%), MKK7 (412%), JNK (680%) TNF-α (300%) genes Additionally, histopathological examination that cisplatin-induced interstitial congestion, focal mononuclear cell inflammatory, infiltrate, acute tubular injury reactive atypia apoptotic cells. Rutin attenuated alteration structural functional changes kidney. confirmed data. suggested anti-oxidant anti-inflammatory may prevent CP-induced via decreasing oxidative stress, inhibiting interconnected ROS/JNK/TNF/P38 MAPK signaling pathways, repairing administration.

Language: Английский

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β-Elemene: Mechanistic Studies on Cancer Cell Interaction and Its Chemosensitization Effect

Frontiers in Pharmacology, Journal Year: 2017, Volume and Issue: 08

Published: March 9, 2017

Over the past decade, screening and identifying novel compounds for their biomedical applications has become an upcoming area of research. Identifying molecular mechanisms these integral part anticancer β-elemene, a sesquiterpene, is renowned its activity against variety cell lines. Recent studies on β-elemene have elucidated that it possesses anti-proliferative effect cancer cells by creating apoptotic trigger. Interestingly, also induces protective autophagy in some cancerous lines less cytotoxic compared to other widely accepted chemotherapeutic agents. This provides edge with perception limited toxicity normal cells. mini-review precisely focuses performed identify mechanism multiple origin. In accordance evaluation made mentioned, apoptosis been identified be most possible reason behind exerted Cell cycle arrest necrosis credited alternate β-elemene.

Language: Английский

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Fish Scale Collagen Peptides Protect against CoCl₂/TNF‐α‐Induced Cytotoxicity and Inflammation via Inhibition of ROS, MAPK, and NF‐κB Pathways in HaCaT Cells

Oxidative Medicine and Cellular Longevity, Journal Year: 2017, Volume and Issue: 2017(1)

Published: Jan. 1, 2017

Skin diseases associated with inflammation or oxidative stress represent the most common problem in dermatology. The present study demonstrates that fish scale collagen peptides (FSCP) protect against CoCl2-induced cytotoxicity and TNF-α-induced inflammatory responses human HaCaT keratinocyte cells. Our is first to report FSCP increase cell viability ameliorate injury cells through mechanisms mediated by downregulation of key proinflammatory cytokines, namely, TNF-α, IL-1β, IL-8, iNOS. also prevent apoptosis repressing Bax expression, caspase-3 activity, cytochrome c release upregulating Bcl-2 protein levels CoCl2- TNF-α-stimulated In addition, inhibitory effects on induction cytokine expression were found be suppression ROS, MAPK (p38/MAPK, ERK, JNK), NF-κB signaling pathways. Taken together, our data suggest are useful as immunomodulatory agents immune-mediated skin diseases. Furthermore, results provide new insights into potential therapeutic use prevention treatment various oxidative- stress-related injuries.

Language: Английский

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