DHA Effect on Chemotherapy-Induced Body Weight Loss: An Exploratory Study in a Rodent Model of Mammary Tumors

Hajjaji, Nawale; Couet, Charles; Besson, Pierre; Bougnoux, Philippe

doi:10.1080/01635581.2012.714832

Cited by 24 publications

(16 citation statements)

References 41 publications

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“…In fact, knowledge on the treatment of muscle wasting is still at its infancy and additional confirmatory studies are needed, especially in cancer cachexia, which is further impaired by chemotherapy (Xue et al, 2011;Hajjaji et al, 2012;Garcia et al, 2013). Previous investigations showed that nutrition modulation using several nutrients (Xue et al, 2011;Hajjaji et al, 2012) and ghrelin (Garcia et al, 2013) may prevent body weight loss in cancer patients undergoing chemotherapy. Moreover, the metabolic modulator trimetazidine was also shown to activate protein synthesis signaling, while decreasing E3 ligase and myostatin levels in experimental models (Ferraro et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Strategies in Lung Cancer-Induced Cachexia: Effects on Muscle Proteolysis, Autophagy, Structure, and Weakness

et al. 2014

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Cachexia is a relevant comorbid condition of chronic diseases including cancer. Inflammation, oxidative stress, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPK) are involved in the pathophysiology of cancer cachexia. Currently available treatment is limited and data demonstrating effectiveness in in vivo models are lacking. Our objectives were to explore in respiratory and limb muscles of lung cancer (LC) cachectic mice whether proteasome, NF-κB, and MAPK inhibitors improve muscle mass and function loss through several molecular mechanisms. Body and muscle weights, limb muscle force, protein degradation and the ubiquitin-proteasome system, signaling pathways, oxidative stress and inflammation, autophagy, contractile and functional proteins, myostatin and myogenin, and muscle structure were evaluated in the diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing cachectic mice (BALB/c), with and without concomitant treatment with NF-κB (sulfasalazine), MAPK (U0126), and proteasome (bortezomib) inhibitors. Compared to control animals, in both respiratory and limb muscles of LC cachectic mice: muscle proteolysis, ubiquitinated proteins, autophagy, myostatin, protein oxidation, FoxO-1, NF-κB and MAPK signaling pathways, and muscle abnormalities were increased, while myosin, creatine kinase, myogenin, and slow- and fast-twitch muscle fiber size were decreased. Pharmacological inhibition of NF-κB and MAPK, but not the proteasome system, induced in cancer cachectic animals, a substantial restoration of muscle mass and force through a decrease in muscle protein oxidation and catabolism, myostatin, and autophagy, together with a greater content of myogenin, and contractile and functional proteins. Attenuation of MAPK and NF-κB signaling pathway effects on muscles is beneficial in cancer-induced cachexia.

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Section: Discussionmentioning

confidence: 99%

Pharmacological Strategies in Lung Cancer-Induced Cachexia: Effects on Muscle Proteolysis, Autophagy, Structure, and Weakness

et al. 2014

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“…[48,49] Surprisingly, however, doxorubicin-induced cachexia was significantly dependent on the tumor TLR9-expression status. Several cytokines have been shown to mediate cachexia, including IL-8, TNF-α and MIC-1.…”

Section: Discussionmentioning

confidence: 99%

DNA from dead cancer cells induces TLR9-mediated invasion and inflammation in living cancer cells

Tuomela

Sandholm

Kaakinen

et al. 2013

Breast Cancer Res Treat

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TLR9 is a cellular DNA-receptor, which is widely expressed in breast and other cancers. Although synthetic TLR9-ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology has remained unclear. We show here that living cancer cells uptake DNA from chemotherapy-killed cancer cells. We discovered that such DNA induces TLR9- and cathepsin-mediated invasion in living cancer cells. To study whether this phenomenon contributes to treatment responses, triple negative, human MDA-MB-231 breast cancer cells stably expressing control or TLR9 siRNA were inoculated orthotopically into nude mice. The mice were treated with vehicle or doxorubicin. The tumor groups exhibited equal decreases in size in response to doxorubicin. However, while the weights of vehicle-treated mice were similar, mice bearing control siRNA tumors became significantly more cachectic in response to doxorubicin, as compared with similarly treated mice bearing TLR9 siRNA tumors, suggesting a TLR9-mediated inflammation at the site of the tumor. In conclusion, our findings propose that DNA released from chemotherapy-killed cancer cells has significant influence on TLR9-mediated biological effects in living cancer cells. Through these mechanisms, tumor TLR9 expression may affect treatment responses to chemotherapy.

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“…), dietary intake has also been shown to not be reduced in rats treated chronically with DOX (Hajjaji et al. ). Nonetheless, future studies are needed to discern the impact of changes in dietary‐intake on chemotherapy‐induced myotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Chronic doxorubicin administration impacts satellite cell and capillary abundance in a muscle‐specific manner

et al. 2019

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Anthracycline chemotherapies are effective at reducing disease recurrence and mortality in cancer patients. However, these drugs also contribute to skeletal muscle wasting and dysfunction. The purpose of this study was to assess the impact of chronic doxorubicin ( DOX ) administration on satellite cell and capillary densities in different skeletal muscles. We hypothesized that DOX would reduce satellite cell and capillary densities of the soleus ( SOL ) and extensor digitorum longus ( EDL ) muscles, along with muscle fiber size. Ovariectomized female Sprague‐Dawley rats were randomized to receive three bi‐weekly intraperitoneal injections of DOX (4 mg∙kg −1 ; cumulative dose 12 mg∙kg −1 ) or vehicle ( VEH ; saline). Animals were euthanized 5d following the last injection and the SOL and EDL were dissected and prepared for immunohistochemical and RT ‐ qPCR analyses. Relative to VEH , CSA of the SOL and EDL fibers were 26% and 33% smaller, respectively, in DOX ( P < 0.05). In the SOL , satellite cell and capillary densities were 39% and 35% lower, respectively, in DOX ( P < 0.05), whereas in the EDL satellite cell and capillary densities were unaffected by DOX administration ( P > 0.05). Proliferating satellite cells were unaffected by DOX in the SOL ( P > 0.05). In the SOL , MYF 5 mRNA expression was increased in DOX ( P < 0.05), while in the EDL MGF mRNA expression was reduced in DOX ( P < 0.05). Chronic DOX administration is associated with reduced fiber size in the SOL and EDL ; however, DOX appeared to reduce satellite cell and capillary densities only in the SOL . These findings highlight that therapeutic targets to protect skeletal muscle from DOX may vary across muscles.

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DHA Effect on Chemotherapy-Induced Body Weight Loss: An Exploratory Study in a Rodent Model of Mammary Tumors

Cited by 24 publications

References 41 publications

Pharmacological Strategies in Lung Cancer-Induced Cachexia: Effects on Muscle Proteolysis, Autophagy, Structure, and Weakness

Pharmacological Strategies in Lung Cancer-Induced Cachexia: Effects on Muscle Proteolysis, Autophagy, Structure, and Weakness

DNA from dead cancer cells induces TLR9-mediated invasion and inflammation in living cancer cells

Chronic doxorubicin administration impacts satellite cell and capillary abundance in a muscle‐specific manner

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