title: Obesity induced rapid melanoma progression is reversed by orlistat treatment and dietary intervention: role of adipokines.
abstract: Obesity, owing to adiposity, is associated with increased risk and development of various cancers, and linked to their rapid growth as well as progression. Although a few studies have attempted to understand the relationship between obesity and melanoma, the consequences of controlling body weight by reducing adiposity on cancer progression is not well understood. By employing animal models of obesity, we report that controlling obesity either by orlistat treatment or by restricting caloric intake significantly slows down melanoma progression. The diminished tumor progression was correlated with decreased fat mass (adiposity) in obese mice. Obesity associated factors contributing to tumor progression were decreased in the experimental groups compared to respective controls. In tumors, protein levels of fatty acid synthase (FASN), caveolin (Cav)-1 and pAkt, which are tumor promoting molecules implicated in melanoma growth under obese state, were decreased. In addition, increased necrosis and reduction in angiogenesis as well as proliferative markers PCNA and cyclin D1 were observed in tumors of the orlistat treated and/or calorically restricted obese mice. We observed that growth of melanoma cells cultured in conditioned medium (CM) from orlistat-treated adipocytes was reduced. Adipokines (leptin and resistin), via activating Akt and modulation of FASN as well as Cav-1 respectively, enhanced melanoma cell growth and proliferation. Together, we demonstrate that controlling body weight reduces adipose mass thereby diminishing melanoma progression. Therefore, strategic means of controlling obesity by reduced caloric diet or with antiobesity drugs treatment may render obesity-promoted tumor progression in check and prolong survival of patients.
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411 007, India.
authors.forename: Parmanand
authors.initials: P
authors.lastname: Malvi
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411 007, India.
authors.forename: Balkrishna
authors.initials: B
authors.lastname: Chaube
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411 007, India.
authors.forename: Vimal
authors.initials: V
authors.lastname: Pandey
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411 007, India.
authors.forename: Maleppillil Vavachan
authors.initials: MV
authors.lastname: Vijayakumar
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411 007, India.
authors.forename: Purushotham Reddy
authors.initials: PR
authors.lastname: Boreddy
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411 007, India.
authors.forename: Naoshad
authors.initials: N
authors.lastname: Mohammad
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411 007, India.
authors.forename: Shivendra Vikram
authors.initials: SV
authors.lastname: Singh
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411 007, India. Electronic address: manojkbhat@nccs.res.in.
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Bhat
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D054392:Adipokines / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004032:Diet; D059305:Diet, High-Fat; D018450:Disease Progression; D005260:Female; D006801:Humans; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use*; D020738:Leptin / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009765:Obesity / Q000150:complications*; D000077403:Orlistat; D052243:Resistin / Q000378:metabolism; D012878:Skin Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology
chemical_list: D054392:Adipokines; D007783:Lactones; D020738:Leptin; D052243:Resistin; D000077403:Orlistat
keywords: Adipokines; Adiposity; Diet; Melanoma; Obesity; Orlistat