Premature Mitochondrial Senescence and Related Ultrastructural Changes during Lung Carcinogenesis Modulation by Curcumin and Resveratrol

Abstract

The present study attempted to explore the efficacy of curcumin and resveratrol in modulating premature mitochondria senescence and ultrastructural changes during lung carcinogenesis. The mice were segregated into 5 groups, which included normal control, benzo[a]pyrene (BP) treated, BP + curcumin (C) treated, BP + resveratrol (R) treated, and BP + C + R treated groups. Animals were given a single ip injection of benzo[a]pyrene in corn oil at a dose level of 100 mg/kg body weight. Treatments of curcumin and resveratrol were given orally in drinking water at a dose level of 60 mg/kg body weight and 5.7 µg/mL drinking water, respectively, 3 times a week for a total duration of 22 weeks. Ultrastructure of BP-treated mice revealed disruptions in cellular integrity along with nuclear deformation and premature mitochondrial senescence. Interestingly, supplementation of curcumin and resveratrol individually resulted in improvement of ultrahistoarchitecture of BP-treated mice but the improvement was much greater with combined supplementation of phytochemicals. Further, benzo[a]pyrene treatment revealed alterations in lung histoarchitecture, which, however, was improved appreciably following combined supplementation with curcumin and resveratrol. The present study concludes that combined supplementation with curcumin and resveratrol effectively modulates histoarchitecture as well as ultrahistoarchitecture during benzo[a]pyrene-induced lung carcinogenesis in mice. Cancer is a public health problem worldwide. Lung cancer is a major cause of mortality throughout the world and is responsible for the deaths of more than one million people annually. Phytochemicals have shown great potential in preventing the occurrence of cancer and other chronic diseases that result from oxidative stress induced by free radicals. Phytochemicals are nonnutritive products of plants and, being nontoxic, are presently being studied the world over for their chemopreventive actions in controlling various diseases, including cancer. In the present study, curcumin and resveratrol are the phytochemicals of interest. Curcumin, a polyphenol, has been reported to have anti-invasive properties. Further, curcumin has been shown to activate apoptotic machinery in patients with lung cancer. On the other hand, resveratrol (trans-3,4,5- thihydroxystibene) is a phytoalexin that is present naturally in grapes as well as in a variety of medicinal plants and has been shown to exhibit antioxidant activity with a potential to induce apoptosis.

Mitochondrial DNA Copy Number and Exposure to Polycyclic Aromatic Hydrocarbons

“…In the present study, we investigated cokeoven workers occupationally exposed to polycyclic aromatic hydrocarbons (PAHs), an established class of lung carcinogens (3,4) and pro-aging compounds (5,6). PAHs are also widespread in the general population due to tobacco smoking, diets, and environmental pollution (3,7).…”

Combination Approach: the Future of the War Against Cancer

“…In this way, these multiple extensive studies contribute toward development and execution of multi-agent chemoprevention trials in humans that in turn resulted in significant treatment advances for the patients with childhood tumors, leukemias, lymphomas, and germinal cell neoplasms [5]. Various studies from our lab also established the efficacy of combination approach in the area of chemoprevention against lung cancer [6][7][8][9].…”

Hidrocarburos aromáticos policíclicos (HAPs) (I): Medidas de prevención y control

“…Para la realización de un estudio clínico en ratones Malhotra et al (2012) dividieron la población en 5 grupos: un control, uno tratado con B[a]P, otro con B[a]P y curcumina, otro con B[a]P y resveratrol y finalmente otro con los tres compuestos. Los ratones tratados con B[a]P desarrollaron alteraciones de la integridad estructural de las células pulmonares, incluyendo deformación del núcleo y envejecimiento mitocondrial prematuro.…”