Z-505 hydrochloride, an orally active ghrelin agonist, attenuates the progression of cancer cachexia via anabolic hormones in Colon 26 tumor-bearing mice

Yoshimura, Masashi; Shiomi, Yoshihiro; Ohira, Yuta; Takei, Makoto; Tanaka, Takao

doi:10.1016/j.ejphar.2017.05.036

Cited by 17 publications

(9 citation statements)

References 48 publications

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“…Reportedly, GHS enhance GH secretion [81], exert anti-inflammatory [85][86][87] and anti-convulsivant actions [88], increase food intake, body weight, and lean body mass (LBM) [81,89], play a role in the regulation of bone metabolism [90], display effects on gastric acid secretion and gastric emptying [91][92][93], and possess protective activity on the cardiovascular system both in vitro [94,95] and in vivo, both in animals [96][97][98] and humans [99,100]. GHS also prevent skeletal muscle damage in muscle wasting conditions associated to cancer cachexia [101][102][103] and/or cancer chemotherapy [8,9,36]. Indeed, because of positive effects on energy balance, ghrelin or GHS are considered a possible treatment option for all these cachexia-related conditions.…”

Section: Growth Hormone Secretagoguesmentioning

confidence: 99%

“…HM01, a novel orally available GHS-R1a agonist, is endowed of a high affinity for the GHS-R1a, good brain permeability, and a longer plasma half-life compared with ghrelin [93]. HN01 has also been tested in different tumor-bearing hosts [101][102][103] characterized by reduced muscle protein synthesis due to catabolism activation, as a result of a complex inflammatory, endocrine, and nutrition-related effect [108]. In rat Morris-7777 hepatoma tumor model, chronic subcutaneous HM01 injections antagonized tumor anorexia and body weight loss, reduced muscle wasting, by enhancing gastrocnemius, soleus, and total muscle mass [101].…”

Section: Growth Hormone Secretagoguesmentioning

confidence: 99%

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

Conte

Bresciani

Rizzi

et al. 2020

IJMS

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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.

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Section: Growth Hormone Secretagoguesmentioning

confidence: 99%

Section: Growth Hormone Secretagoguesmentioning

confidence: 99%

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

Conte

Bresciani

Rizzi

et al. 2020

IJMS

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“…55,112) It was also reported that the nonpeptidergic ghrelin receptor agonist counteracts cachectic body weight loss under inflammatory conditions. [113][114][115] 5.6. MicroRNA (miRNA) Increased miR27a/b was reported to negatively regulate the expression of myostatin.…”

Section: Ast-120mentioning

confidence: 99%

Sarcopenia in Chronic Kidney Disease: Factors, Mechanisms, and Therapeutic Interventions

Watanabe

Enoki

Maruyama

2019

Biological & Pharmaceutical Bulletin

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Chronic kidney disease (CKD), a chronic catabolic condition, is characterized by muscle wasting and decreased muscle endurance. Many insights into the molecular mechanisms of muscle wasting in CKD have been obtained. A persistent imbalance between protein degradation and synthesis in muscle causes muscle wasting. During muscle wasting, high levels of reactive oxygen species (ROS) and inflammatory cytokines are detected in muscle. These increased ROS and inflammatory cytokine levels induce the expression of myostatin. The myostatin binding to its receptor activin A receptor type IIB stimulates the expression of atrogenes such as atrogin-1 and muscle ring factor 1, members of the muscle-specific ubiquitin ligase family. Impaired mitochondrial function also contributes to reducing muscle endurance. The increased protein-bound uremic toxin, parathyroid hormone, glucocorticoid, and angiotensin II levels that are observed in CKD all have a negative effect on muscle mass and endurance. Among the protein-bound uremic toxins, indoxyl sulfate, an indole-containing compound has the potential to induce muscle atrophy by stimulating ROS-mediated myostatin and atrogenes expression. Indoxyl sulfate also impairs mitochondrial function. Some potential therapeutic approaches based on the muscle wasting mechanisms in CKD are currently in the testing stages.

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“…A study demonstrated that Z-505 notably improved appetite, reduced muscle wasting, prevented weight loss, and augmented anabolic factors like insulin and IGF-1 [163]. However; it did not increase levels of catabolic factors like IL-6 and corticosterone [163]. Another recent study showed that Z-505 improved cisplatin and 5-FU-induced anorexia via stimulation of GHSR1a, signifying its utility in the protective management of loss of appetite during chemotherapy [164].…”

Section: Z-505 Hydrochloride (Z-505)mentioning

confidence: 99%

Section: Z-505 Hydrochloride (Z-505)mentioning

confidence: 99%

Ghrelin as a Promising Therapeutic Option for Cancer Cachexia

Khatib

Gaidhane

et al. 2018

Cell Physiol Biochem

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Cachexia is a devastating complication of cancer and an important cause of morbidity and mortality and can have a great effect on quality of life, and sense of self-esteem. Unfortunately; there is no standard cure available for cancer cachexia. Ghrelin; a 28 amino acid orexigenic gut hormone and its mimetics have shown potential benefits in reversing the breakdown of protein and weight loss in catabolic states like cancer cachexia. Ghrelin has effects on several vital pathways in the regulation of appetite, and composition of the body. It increases the secretion of growth hormone and reduces energy expenditure. It plays an important role in regulation of processes associated with cancer and antagonizing protein breakdown in catabolic conditions such as cancer cachexia. Additionally, ghrelin has anti-inflammatory, anti-apoptotic and anxiolytic effects. Administration of ghrelin for short-term has been found to be well-tolerated and safe. These versatile actions of ghrelin and its safety can render it as a potentially useful novel therapy for patients with cancer cachexia. However; there is a need to generate more evidence to support the use of ghrelin in the management of cancer cachexia.

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Z-505 hydrochloride, an orally active ghrelin agonist, attenuates the progression of cancer cachexia via anabolic hormones in Colon 26 tumor-bearing mice

Cited by 17 publications

References 48 publications

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

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

Sarcopenia in Chronic Kidney Disease: Factors, Mechanisms, and Therapeutic Interventions

Ghrelin as a Promising Therapeutic Option for Cancer Cachexia

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