In a study published in the journal Frontiers in Pharmacology, researchers from the USA explored the potential chemopreventive effects of a mushroom-derived commercial product called GLSF, derived from Ganoderma lucidum (GL). The study involved both in vitro experiments and tests on mice with lung carcinogenesis induced by two tobacco smoke carcinogens: benzo[a]pyrene (B[a]P) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The results indicated that mice treated with GLSF exhibited decreased lung toxicity caused by B[a]P and a reduced development of lung tumors induced by NNK.
Background of the Study
Lung cancer ranks among the primary causes of cancer-related fatalities worldwide, with the majority of lung cancer deaths attributed to both direct tobacco smoking and secondhand smoke exposure. Substances such as NNK and B[a]P found in tobacco smoke are recognized as procarcinogens capable of instigating deoxyribonucleic acid (DNA) mutations that ultimately lead to lung cancer. Existing treatments for this disease are constrained by their adverse side effects and the emergence of treatment resistance. Consequently, there is an imperative need to identify and develop natural products with chemopreventive attributes that could complement therapy and hinder the progression of cancer in patients.
A specific medicinal mushroom, known as GL, possesses well-documented anticancer and immunomodulating properties and has been employed as a nutraceutical in the management of various chronic conditions, including cancer. Nevertheless, the potential of GL or GL-derived products for preventing lung carcinogenesis induced by tobacco smoking has not yet been explored. In the present study, researchers aimed to gather preclinical evidence regarding the potential effects of GLSF, a formulation comprising the spore and fruiting body of GL in a 30:8 ratio, on lung carcinogenesis in mice induced by NNK and B[a]P.
Details on the Study
A previously established protocol was followed to prepare GLSF extract. The objective of the study was to explore the impact of GLSF on the initial stage of tumor formation, known as single-cell transformation. In the in vitro phase, 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, was used. To confirm this effect in vivo, mouse models were exposed to a single acute dose of B[a]P over 24 hours. Lung toxicity was assessed through lactate dehydrogenase (LDH) activity assay, lipid hydroperoxide (LPO) assay, histology, and immunohistology analysis.
For the long-term carcinogenesis study, mice were intraperitoneally injected with NNK twice a week for 33 weeks. The resulting tumors and their growth were evaluated based on lung weight, tumor area, and tumor burden. Inflammation, angiogenesis, and apoptosis are known to influence cancer initiation and progression. Therefore, the expression of key markers of inflammation and angiogenesis (Cox-2, NF-kB, and VEGF-A), as well as apoptosis (cleaved-caspase-3 and cleaved-PARP), was measured in the lung tissues.
Results and Further Discussion
In the realm of laboratory experiments, GLSF demonstrated a remarkable ability to impede the transformation of BEAS-2B cells induced by BPDE, a well-known carcinogenic agent. This inhibition suggests that GLSF could play a pivotal role in managing the cellular changes caused by exposure to such harmful substances in bronchial epithelial cells. These findings, in sync with existing scientific literature, underscore the promising potential of GLSF in the field of cancer research.
In a concise study involving mice subjected to short-term exposure, B[a]P was found to wreak havoc on the intricate architecture of the lungs and alveoli. Simultaneously, it led to an increased infiltration of inflammatory cells, a clear indication of lung damage. However, when the mice were pre-treated with GLSF, a notable reduction in B[a]P-induced lung toxicity was observed. This reduction was evidenced not only by the visibly improved structure of lung tissues but also by lower levels of LDH activity, malondialdehyde, and reduced infiltration of inflammatory cells. Strikingly, GLSF exhibited a protective effect comparable to that of curcumin, a well-known anti-inflammatory and antioxidant compound.
In a more extended study focused on carcinogenesis, mice treated with NNK displayed a significant increase in lung weight and upregulation of inflammatory and angiogenesis markers, highlighting the progression of cancerous changes. However, in line with predictions, GLSF treatment resulted in a substantial decrease in lung weight and tumor area. Moreover, fewer tumors were observed in the lungs of mice treated with GLSF in combination with metformin. Intriguingly, the GLSF group exhibited a decrease in inflammatory and angiogenesis markers, comparable in efficacy to metformin. Furthermore, there was an increase in apoptotic markers, suggesting that GLSF holds significant promise as a preventive agent against lung cancer.
What adds to GLSF’s appeal is its status as a nutraceutical, a natural compound derived from food sources with purported health benefits. Notably, there is no record of GLSF being associated with any severe adverse events. This safety profile positions GLSF as an ideal candidate for future clinical studies focused on lung cancer prevention. The implications of these findings are profound, opening avenues for further research and clinical exploration, potentially leading to a groundbreaking approach in the prevention and management of lung cancer.
Conclusion Made
According to the research findings, GLSF exhibits preventive properties both in laboratory experiments (in vitro) and in living organisms (in vivo) against lung cancer caused by tobacco smoking. While additional research is necessary to validate these findings, this initial evidence sets the stage for future clinical trials. Depending on the outcomes of these trials, GLSF might be considered for use in individuals at high risk of developing lung cancer, particularly heavy smokers.
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