Lung cancer is one of the leading causes of cancer mortality worldwide, and most lung cancer deaths are caused by tobacco smoking and second-hand smoking. NNK and benzopyrene (BaP) are known procarcinogens in tobacco smoke that can lead to DNA mutations and, eventually, lung cancer. The conventional therapies for this disease are limited owing to their adverse effects and the development of resistance against them. There is thus an urgent need to identify and develop natural products with chemopreventive properties that could support therapy and inhibit cancer development in patients. A medicinal mushroom, Ganoderma Lucidum (GAL) is known to have active princiles (mainly saponins or hydroxy-steroids) with anticancer and immunomodulating properties and has been employed as a nutraceutical in the treatment of various chronic ailments, including cancer.
However, the effects of GAL or GAL-derived products have not been studied for the prevention of tobacco-smoking-induced lung carcinogenesis. In a preclinical study published in the journal Frontiers in Pharmacology, researchers from the USA investigated the potential chemopreventive effects of Ganoderma lucidum (GAL)-derived commercial product, named GLSF, in vitro and in mice with lung carcinogenesis induced benzopyrene and 4-NNK. They found that mice treated with GLSF had lower BaP-induced lung toxicity and reduced NNK-induced lung tumor development. To study the effect of GLSF extract on single-cell transformation, which is the initial phase in tumor formation, the in vitro segment of the study made use of the BEAS-2B cell line, a normal human bronchial epithelial cell line transformable by BPDE, an active form of BaP.
To verify this effect of GLSF in vivo, mouse models were developed by giving them a single dose of acute 24-hour BaP exposure. Further, to study long-term carcinogenesis, NNK was injected intraperitoneally in mice twice a week for 33 weeks. The resultant tumors and their growth were evaluated based on lung weight, tumor area and tumor burden. The expression of markers of inflammation and angiogenesis (COX2, NF-kB and VEGF-A) and those of apoptosis (cleaved caspases) was also measured in the lung tissues. In the in vitro experiments, GLSF was found to inhibit the BPDE-induced transformation of bronchial cells, corroborating with existing literature.In the short-term exposure study in mice, BaP was found to disrupt the architecture of the lung and alveoli while causing an increased infiltration of inflammatory cells.
However, pretreating the mice with GLSF was found to reduce BaP-induced lung toxicity (with an efficacy comparable to curcumin), as demonstrated by the improved histology of the harvested lung tissue samples. In the long-term carcinogenesis study, the mice treated with NNK increased the expression of inflammatory and angiogenesis markers compared to the control. As predicted, treatment of mice with GLSF showed a significant decrease in lung weight and tumor area. Additionally, a lesser number of tumors were observed in the lungs of mice treated with GLSF and metformin. Inflammatory and angiogenesis markers were found to decrease in the GLSF group (with an efficacy comparable to that of metformin). On the other hand, apoptotic markers were found to increase, indicating the ability to promote the clearance of damaged/promoted cells.
As a nutraceutical, GLSF is not known to be associated with any severe adverse event, making it an ideal candidate for future clinical studies aimed at lung cancer prevention. As per the study, GLSF demonstrates preventive abilities in vitro and in vivo against tobacco-smoking-induced lung carcinogenesis. Although clinical trials are surely required to confirm the results of this study, this preliminary evidence paves the way for their planning in the future. Subject to trial results, GLSF could potentially be utilized in individuals with an increased risk of developing lung cancer, such as heavy smokers.
- Edited by Dr.Gianfrancesco Cormaci, PhD; specialist in Clinical Biochiemistry.
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