Platinum-induced muscle wasting in cancer chemotherapy: Mechanisms and potential targets for therapeutic intervention

Santos

J cachexia sarcopenia muscle

et al. 2020

Self Cite

219

191

Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass, along with adipose tissue wasting, systemic inflammation and other metabolic abnormalities leading to functional impairment. Cancer cachexia has long been recognized as a direct cause of complications in cancer patients, reducing quality of life and worsening disease outcomes. Some related conditions, like sarcopenia (age‐related muscle wasting), anorexia (appetite loss) and asthenia (reduced muscular strength and fatigue), share some key features with cancer cachexia, such as weakness and systemic inflammation. Understanding the interplay and the differences between these conditions is critical to advance basic and translational research in this field, improving the accuracy of diagnosis and contributing to finally achieve effective therapies for affected patients.

Section: Cancer Cachexiamentioning

confidence: 99%

Cancer cachexia and its pathophysiology: links with sarcopenia, anorexia and asthenia

Santos

J cachexia sarcopenia muscle

et al. 2020

Self Cite

219

191

“…Cisplatin induces TNF-α and IL-1 overexpression causing IkB kinase (IKK) complex activation, and leading to the phosphorylation of the NF-κB-bound inhibitors of NF-κB (IκBs), which are consequently ubiquitinated and degraded. This leads to nuclear translocation of activated NF-κB which then induces the expression of MAFbx/atrogin-1 and MuRF1 favoring muscle wasting and cachexia [56]. At the same time, IL-6, whose expression is also induced by cisplatin, can bind its receptor IL-6R causing homodimerization of gp130.…”

Section: Oxidative Stress and Pro-inflammatory Cytokinesmentioning

confidence: 99%

“…At the same time, IL-6, whose expression is also induced by cisplatin, can bind its receptor IL-6R causing homodimerization of gp130. This homodimerization activates the associated JAKs (Janus kinases) resulting in the activation of transcription factors of the signal transducer and activator of transcription (STAT) family suppressing protein synthesis [55,56].…”

Section: Oxidative Stress and Pro-inflammatory Cytokinesmentioning

confidence: 99%

Cisplatin-Induced Skeletal Muscle Dysfunction: Mechanisms and Counteracting Therapeutic Strategies

Conte

Bresciani

Rizzi

et al. 2020

IJMS

Among the severe side effects induced by cisplatin chemotherapy, muscle wasting is the most relevant one. This effect is a major cause for a clinical decline of cancer patients, since it is a negative predictor of treatment outcome and associated to increased mortality. However, despite its toxicity even at low doses, cisplatin remains the first-line therapy for several types of solid tumors. Thus, effective pharmacological treatments counteracting or minimizing cisplatin-induced muscle wasting are urgently needed. The dissection of the molecular pathways responsible for cisplatin-induced muscle dysfunction gives the possibility to identify novel promising therapeutic targets. In this context, the use of animal model of cisplatin-induced cachexia is very useful. Here, we report an update of the most relevant researches on the mechanisms underlying cisplatin-induced muscle wasting and on the most promising potential therapeutic options to preserve muscle mass and function.

“…Remarkably, P. purpurogenum's extracellular extract was able to improve mouse survival at all doses, compared with the negative control and even with cyclophosphamide, providing 100% survival at the end of the study. The extract preserved body weight of the animals, preventing the wasting syndrome that is often associated with cancer and intensified by chemotherapy [55,56,57,58,59], as previously reviewed [60,61].…”

Section: P Purpurogenum Extract Showed Activity Against Ehrlich's Somentioning

confidence: 80%

Penicillium purpurogenumexerts antitumor effects and ameliorates inflammations in Erlich mice model

Teles

Pontes

Guimarães

et al. 2020

Preprint

ABSTRACTBackgroundThe bioactive metabolites production contributes to the resistance of fungi towards adverse environmental conditions. Some metabolites often have interesting health-promoting activities. This study addressed the anti-tumoural properties of Penicillium purpurogenum isolated from a polluted lagoon in Northeastern Brazil.MethodsThe extract obtained from the polished environment strain P. purpurogenum was fermented, filtered, concentrated and lyophilized, giving rise to the Ethyl Acetate Extracellular Extract (EAE). The metabolites of the extracellular extract of P. purpurogenum were studied using direct infusion mass spectrometry. The solid Ehrlic tumor model was used to evaluate the extract antitumor activity. Female Swiss mice were divided in groups (n=10/group) as follow: Negative control (CTL-) treated with phosphate buffered solution; Positive Control (CTL+) treated with cyclophosphamide (25mg/mL); Extracts treatment at doses 4, 20 and 100mg/Kg; Animals without tumor or treatment (Sham); and animals without tumor treated with intermediate dose (EAE20). All treatments were performed intraperitoneally, daily during 15 days. After, the animals were eutanized and the tumor, lymphoid organs and serum were used for immunological, histological and biochemical parameters evaluation.ResultsThe extract was rich in meroterpenoids. All doses of the extract significantly reduced tumor size compared to CLT- and were associated with 100% survival. Histologically, the 20 and 100mg/kg doses reduced tumour-associated inflammation and tumour necrosis. The extract also reduced cellular infiltration of lymphoid organs and circulating TNF-α levels when compared with CLT-. The extract did not induce weight loss and renal or hepatic toxic changes.ConclusionsThese results indicate that P. purpurogenum from a polluted marine environment produce hybrid natural products of the terpenoid pathway that exhibits immunomodulatory and antitumor properties in vivo. Thus, fungal fermentation is a biotechnological approach for the production of antitumour agents.