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cells, dtic, mice, melanoma, cancer, obesity, pubmed, serum, article, tumor, google, scholar, hfd, fig, treatment, orlistat, medium, obese, survival, factors, pgp, cas, cultured, response, data, weight, collected, fasn, additional, days, cav, diet, obesityassociated, file, interventions, outcome, experimental, treated, control, therapy, adipocytes, drug, increased, levels, figure, growth, progression, group, cblj, tumors,

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springer nature author information authors figures s1 agilent zorbax sb-c18 sudarslal sadasivan nair methods experimental animals manoj kumar bhat discussion state privacy rights mass spectrometry-related experiments additional files 1 male c57bl/6j mice employed lc-ms/ms chemo-resistant phenotype induced thirty-year experience overview lc-ms/ms analysis hrp-conjugated secondary antibodies maleppillil vavachan vijayakumar long-term survival assay sds-page anti–apoptotic transcriptional programs hfd c57bl/6j mice lc-esi ms/ms develop drug-resistant phenotype utilized 3t3-l1 cells weight-control interventions weight control interventions experimental c57bl/6j mice fda-approved cytotoxic drug promote drug-resistant phenotype serum-free fatty acids differentiated 3t3-l1 cells 3t3-l1 cells differentiated central instrumental facilities diet-induced obesity impairs hyderabad central university adiposity-related cellular obese background counteracting neoplasia-promoting role rights weight loss interventions verify long-term survival inducing dna damage background obesity regulating drug-resistant phenotype adipocyte-secretory factors impair adipokine-driven akt activation author correspondence original author diet-induced obese mice

Questions {❓}

• The multidrug transporter P-glycoprotein: a mediator of melanoma invasion?

Schema {🗺️}

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         headline:Weight control interventions improve therapeutic efficacy of dacarbazine in melanoma by reversing obesity-induced drug resistance
         description:Obesity-related cellular, metabolic, and molecular alterations have been shown to increase cancer risk and tumor progression and are associated with poorer therapeutic outcome in cancer patients. However, the impact of obesity and weight-control interventions on the therapeutic response in melanoma is poorly understood. High fat diet (HFD)-induced obese mouse model was used in this study to evaluate the outcome of dacarbazine (DTIC) therapy in melanoma. We employed LC-MS/MS to determine the quantity of the drug in tumor, and in various tissues. Unique in vitro approach was used to complement in vivo findings by culturing melanoma cells in either conditioned medium (CM) obtained from differentiated adipocytes or in serum collected from experimental mice. We report that diet-induced obesity impairs the outcome of DTIC therapy and reduces overall survival in tumor-bearing mice. We provide evidence that obesity restricts the accessibility of DTIC to tumor tissue. Critically, upon curtailing adiposity, accumulation and efficacy of DTIC is significantly improved. Moreover, using appropriate in vitro approaches, we show that melanoma cells exhibit a drug-resistant phenotype when cultured in serum collected from diet-induced obese mice or in CM collected from 3T3-L1 adipocytes. The impaired therapeutic response to DTIC in obese state is mediated by fatty acid synthase (FASN), caveolin-1 (Cav-1), and P-glycoprotein (P-gp). The response to DTIC and overall survival were improved upon employing weight control interventions in the tumor-bearing HFD-fed (obese) mice. This study indicates that obesity not only supports rapid melanoma progression but also impairs the outcome of chemotherapy, which can be improved upon employing weight control interventions. From clinically relevant point of view, our study exemplifies the importance of lifestyle interventions in the treatment of obesity-promoted cancers.
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      description:Obesity-related cellular, metabolic, and molecular alterations have been shown to increase cancer risk and tumor progression and are associated with poorer therapeutic outcome in cancer patients. However, the impact of obesity and weight-control interventions on the therapeutic response in melanoma is poorly understood. High fat diet (HFD)-induced obese mouse model was used in this study to evaluate the outcome of dacarbazine (DTIC) therapy in melanoma. We employed LC-MS/MS to determine the quantity of the drug in tumor, and in various tissues. Unique in vitro approach was used to complement in vivo findings by culturing melanoma cells in either conditioned medium (CM) obtained from differentiated adipocytes or in serum collected from experimental mice. We report that diet-induced obesity impairs the outcome of DTIC therapy and reduces overall survival in tumor-bearing mice. We provide evidence that obesity restricts the accessibility of DTIC to tumor tissue. Critically, upon curtailing adiposity, accumulation and efficacy of DTIC is significantly improved. Moreover, using appropriate in vitro approaches, we show that melanoma cells exhibit a drug-resistant phenotype when cultured in serum collected from diet-induced obese mice or in CM collected from 3T3-L1 adipocytes. The impaired therapeutic response to DTIC in obese state is mediated by fatty acid synthase (FASN), caveolin-1 (Cav-1), and P-glycoprotein (P-gp). The response to DTIC and overall survival were improved upon employing weight control interventions in the tumor-bearing HFD-fed (obese) mice. This study indicates that obesity not only supports rapid melanoma progression but also impairs the outcome of chemotherapy, which can be improved upon employing weight control interventions. From clinically relevant point of view, our study exemplifies the importance of lifestyle interventions in the treatment of obesity-promoted cancers.
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         Adipokines
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         Chemotherapy
         Orlistat
         Weight-control interventions
         Cancer Research
         Oncology
         Metabolomics
         Metabolic Diseases
         Imaging / Radiology
         Cell Biology
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      name:Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, India
      name:Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, India
      name:Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, India
      name:Laboratory No. 6, National Centre for Cell Science (NCCS), Savitribai Phule Pune University Campus, Pune, India

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