Understanding Lung Carcinogenesis from a Morphostatic Perspective: Prevention and Therapeutic Potential of Phytochemicals for Targeting Cancer Stem Cells

Abstract

Lung cancer is still one of the deadliest cancers, with over two million incidences annually. Prevention is regarded as the most efficient way to reduce both the incidence and death figures. Nevertheless, treatment should still be improved, particularly in addressing therapeutic resistance due to cancer stem cells—the assumed drivers of tumor initiation and progression. Phytochemicals in plant-based diets are thought to contribute substantially to lung cancer prevention and may be efficacious for targeting lung cancer stem cells. In this review, we collect recent literature on lung homeostasis, carcinogenesis, and phytochemicals studied in lung cancers. We provide a comprehensive overview of how normal lung tissue operates and relate it with lung carcinogenesis to redefine better targets for lung cancer stem cells. Nine well-studied phytochemical compounds, namely curcumin, resveratrol, quercetin, epigallocatechin-3-gallate, luteolin, sulforaphane, berberine, genistein, and capsaicin, are discussed in terms of their chemopreventive and anticancer mechanisms in lung cancer and potential use in the clinic. How the use of phytochemicals can be improved by structural manipulations, targeted delivery, concentration adjustments, and combinatorial treatments is also highlighted. We propose that lung carcinomas should be treated differently based on their respective cellular origins. Targeting quiescence-inducing, inflammation-dampening, or reactive oxygen species-balancing pathways appears particularly interesting.

Multi-Target Potential of Berberine as an Antineoplastic and Antimetastatic Agent: A Special Focus on Lung Cancer Treatment

“…[ 21 , 30 , 38 ]. Most importantly, few have been approved for the treatment of lung cancer, including Camptothecins (topoisomerase I inhibitors), Taxanes and Vinca alkaloids (Tubulin inhibitors), and Podophyllotoxins (Tubulin/Topoisomerase II inhibitors) [ 30 , 39 ].…”

Sulforaphane: The Principal Broccoli Phytochemical as a Cancer Challenger

“…SFN inhibits not only miR-19 but also the Wnt/β catenin pathway, thus inhibiting LCSC activity and tumor development [89]. SFN targets LCSCs by a few mechanisms [90]. A study of the effect of SFN on the development of A549 non-small lung cancer cell line demonstrated that 30, 60, and 90 µM SFN exerted a dose-dependent effect on G2/M arrest and cell death, with lower D1 cyclin content detected at higher concentrations [91].…”

Cytotoxic effect of cloned EGFP gene on NCI-H727 cell line via genetically engineered gene transfer system

“…Lung cancer is a malignant tumor of the lungs that causes uncontrolled cell development in the tissues (19). Epithelial cells that have become malignant or epithelial cell-containing tissues are the sources of lung carcinogenesis.…”

“…The malignant transformation of connective tissues (nerve, fat, muscle, and bone) that arise from mesenchymal cells is the source of some lung malignancies, such as rare lung sarcomas. Lymphomas and melanomas can potentially be the cause of lung cancer (cells of the lymphoid and melanocyte lineages) (19). Lung cancer the most common among cancers, remains the leading cause of cancer death with an estimated 1.8 million deaths reported in 2020 (19).…”