Ammu V V V Ravi Kiran1, Garikapati Kusuma Kumari1, Praveen T Krishnamurthy2. 1. Department of Pharmacology, JSS College of Pharmacy (JSS Academy of Higher Education & Research) Rocklands, Ooty, The Nilgiris, Tamil Nadu, 643001, India. 2. Department of Pharmacology, JSS College of Pharmacy (JSS Academy of Higher Education & Research) Rocklands, Ooty, The Nilgiris, Tamil Nadu, 643001, India. praveentk7812@gmail.com.
Abstract
PURPOSE: Among the lung cancer types, non-small cell lung cancer (NSCLC) is prominent and less responsive to chemotherapy. The current chemotherapeutics for NSCLC are associated with several dose-limiting side effects like bone-marrow suppression, neurotoxicity, nephrotoxicity, and ototoxicity, etc. which are causing non-compliance in patients. Many tumors, including breasts, lung, ovarian, etc. overexpress PPAR-γ receptors and COX-2 enzymes, which play a crucial role in tumor progression, angiogenesis, and metastasis. Lack of PPAR-γ activation and overproduction of prostaglandins, result in uncontrolled activation of Ras/Raf/Mek ultimately, NF-κB mediated tumor proliferation. This study aimed to investigate the anti-cancer potential of PPAR-γ agonist Pioglitazone combined with COX-2 inhibitor Celelcoxib in NSCLC. METHODS: Sixty adult Balb/C male mice were classified into sham control, disease control, and treatment groups. Mice were treated with Nicotine-derived nitrosamine ketone (NNK) (10 mg/kg), pioglitazone (10 & 20 mg/kg) and celecoxib (25 & 50 mg/kg). Weekly body weight, food intake, mean survival time & % increased life span were determined. Tumor weight and histopathological analysis were performed at the end of the study. RESULTS: The significant tumor reducing potential of pioglitazone combined with celecoxib was observed (p < 0.05). The treatment groups (treated with pioglitazone and celecoxib) showed a remarkable decrease in lung tumor weight, improved life span and mean survival time (p < 0.05). Histopathological studies confirm that treatment groups (treated with pioglitazone and celecoxib) reframed the lung architecture compared to disease control. CONCLUSION: Preliminary results revealed that pioglitazone adjunacy with celecoxib may be an effective chemo-preventive agent against NNK induce NSCLC.
PURPOSE: Among the lung cancer types, non-small cell lung cancer (NSCLC) is prominent and less responsive to chemotherapy. The current chemotherapeutics for NSCLC are associated with several dose-limiting side effects like bone-marrow suppression, neurotoxicity, nephrotoxicity, and ototoxicity, etc. which are causing non-compliance in patients. Many tumors, including breasts, lung, ovarian, etc. overexpress PPAR-γ receptors and COX-2 enzymes, which play a crucial role in tumor progression, angiogenesis, and metastasis. Lack of PPAR-γ activation and overproduction of prostaglandins, result in uncontrolled activation of Ras/Raf/Mek ultimately, NF-κB mediated tumor proliferation. This study aimed to investigate the anti-cancer potential of PPAR-γ agonist Pioglitazone combined with COX-2 inhibitor Celelcoxib in NSCLC. METHODS: Sixty adult Balb/C male mice were classified into sham control, disease control, and treatment groups. Mice were treated with Nicotine-derived nitrosamine ketone (NNK) (10 mg/kg), pioglitazone (10 & 20 mg/kg) and celecoxib (25 & 50 mg/kg). Weekly body weight, food intake, mean survival time & % increased life span were determined. Tumor weight and histopathological analysis were performed at the end of the study. RESULTS: The significant tumor reducing potential of pioglitazone combined with celecoxib was observed (p < 0.05). The treatment groups (treated with pioglitazone and celecoxib) showed a remarkable decrease in lung tumor weight, improved life span and mean survival time (p < 0.05). Histopathological studies confirm that treatment groups (treated with pioglitazone and celecoxib) reframed the lung architecture compared to disease control. CONCLUSION: Preliminary results revealed that pioglitazone adjunacy with celecoxib may be an effective chemo-preventive agent against NNK induce NSCLC.
Authors: S Ricci; A Antonuzzo; L Galli; C Tibaldi; M Bertuccelli; A Lopes Pegna; S Petruzzelli; R Algeri; V Bonifazi; M L Fioretto; C Orlandini; P F Conte Journal: Lung Cancer Date: 2000-02 Impact factor: 5.705
Authors: Richard E Kast; Alex Alfieri; Hazem I Assi; Terry C Burns; Ashraf M Elyamany; Maria Gonzalez-Cao; Georg Karpel-Massler; Christine Marosi; Michael E Salacz; Iacopo Sardi; Pieter Van Vlierberghe; Mohamed S Zaghloul; Marc-Eric Halatsch Journal: Cancers (Basel) Date: 2022-05-23 Impact factor: 6.575
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