In a preclinical study published in the journal Frontiers in Pharmacology, researchers from the USA investigated the potential chemopreventive effects of a mushroom - Ganoderma lucidum (GL)-derived commercial product named GLSF in vitro and in mice with lung carcinogenesis induced by two tobacco smoke carcinogens, namely benzo[a]pyrene (B[a]P) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). They found that mice treated with GLSF had lower B[a]P-induced lung toxicity and reduced NNK-induced lung tumor development.
Study: The medicinal mushroom Ganoderma lucidum prevents lung tumorigenesis induced by tobacco smoke carcinogens. Image Credit: Tei Sinthip / Shutterstock
Background
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 B[a]P are known procarcinogens in tobacco smoke that can lead to deoxyribonucleic acid (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, GL is known to have anticancer and immunomodulating properties and has been employed as a nutraceutical in the treatment of various chronic ailments, including cancer. However, the effects of GL or GL-derived products have not been studied for the prevention of tobacco-smoking-induced lung carcinogenesis. In the present study, researchers aimed to gather preclinical evidence on the potential effects of GLSF, which contains the spore and fruiting body of GL in a 30:8 ratio, on lung carcinogenesis in mice induced by NNK and B[a]P.
About the study
GLSF extract was prepared using a previously described protocol. To study the effect of GLSF 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 non-tumorous human bronchial epithelial cell line transformable by Benzo[a]pyrenediol-epoxide (BPDE), an active form of B[a]P. To verify this effect of GLSF in vivo, mouse models were developed by giving them a single dose of acute 24-hour B[a]P exposure. The lung toxicity was measured using lactate dehydrogenase (LDH) activity assay, lipid hydroperoxide (LPO) assay, histology, and immunohistology analysis.
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 initiation and progression of cancer is also known to be influenced by inflammation, angiogenesis, and apoptosis. Therefore, the expression of important markers of inflammation and angiogenesis (Cox-2, NF-kB, and VEGF-A) and those of apoptosis (cleaved-caspase-3 and cleaved-PARP) was also measured in the lung tissues.
Results and discussion
In the in vitro experiments, GLSF was found to inhibit the BPDE-induced transformation of BEAS-2B cells, indicating its potential role in controlling the cellular alterations resulting from the exposure of these bronchial epithelial cells to known carcinogens. The findings corroborate with existing literature.
In the short-term exposure study in mice, B[a]P was found to disrupt the architecture of the lung and alveoli while causing an increased infiltration of inflammatory cells as compared to the control group. However, pretreating the mice with GLSF was found to reduce B[a]P-induced lung toxicity (with an efficacy comparable to curcumin), as demonstrated by the improved histology of the harvested lung tissue samples, as well as lower LDH activity, malondialdehyde levels, and inflammatory cell infiltration in them.
In the long-term carcinogenesis study, the mice treated with NNK showed a 58.24% increase in lung weight and 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. While inflammatory and angiogenesis markers were found to decrease in the GLSF group (with an efficacy comparable to that of metformin), apoptotic markers were found to increase, indicating GLSF’s promising preventive potential against lung cancer.
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.
Conclusion
As per the study, GLSF demonstrates preventive abilities in vitro and in vivo against tobacco-smoking-induced lung carcinogenesis. Although further research is required to confirm the results of this study, this preliminary evidence paves the way for clinical trials 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.
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