Lung cancer: Animal model of lung cancer, molecular carcinogenesis of lung cancer, and antitumor effect of Ocimum sanctum against lung cancer

Abstract

Lung cancer is the leading cause of fatalities related to cancer globally. There are numerous ways to treat lung cancer, including surgery, chemotherapy, and radiation. Since these treatments have not yet shown satisfactory results, more research into the underlying mechanisms and different approaches to therapy and prevention are needed. Animal models are essential to the study of lung cancer because they offer priceless information about the etiology, course, and possible treatments for the illness. The therapeutic application of phytochemicals and medicinal plants to treat cancer-related compounds has gained attention subsequently. In addition to discussing the molecular carcinogenic and antitumor effects of the herbal treatment Ocimum sanctum (OS) in connection to lung cancer, this review will address the current awareness regarding lung cancer in animal models. The multitude of animal models used in lung cancer research-such as genetically modified mice, carcinogen-induced models, and xenograft induction-provides a solid foundation for understanding the illness. By easing the examination of the environmental and genetic factors involved and enhancing the analysis of possibilities for treatment, these models eventually assist in the further development of lung cancer therapy. Additionally, using the herb plant OS is essential for both treating and preventing lung cancer. Standardizing dosages and enforcing laws on the use of herbal medications require more in-depth investigation.

Keywords: Animal model; Carcinogenesis mechanism; Lung cancer; Ocimum sanctum.

Fig. 1.. The four most frequently used techniques to generate mouse lung cancer models include chemically induced models, PDX mode, CDX model, and genetically engineered mouse model.

Fig. 2.. The OS structure. OS is a perennial plant with a medium stature and a woody base. OS grows to a height of 30–60 cm on a standing-up, multibranched stem with hairy, subquadrangular stems. The oval-shaped, green leaves are narrowed at both ends. The petioles are 1.5–3 cm long and very slender. The petals are clustered into bracteate clusters that are 15–20 cm long on little stems.

Fig. 3.. The development of cancer cells is supported by the angiogenesis that is encouraged by the VEGF. Mutant cells constantly divide, growing bigger and more susceptible to hypoxia. Hypoxic conditions will promote microenvironment cells to secrete VEGF (VEGFA, VEGFB, VEGFC, VEGFD). VEGF will bind to its receptors (VEGFR1, VEGFR2, VEGFR3) and form tip cells on endothelial cells. Tip cells will develop branches (angiogenic sprouts) to form new blood vessel channels. The new blood vessel channels will continue to branch to form vascularization in cancer cells.

Fig. 4.. The interaction of integrins αvβ3 and α5β1 with ECM regulates metastatic activity. The expression of integrin αvβ3 and α5β1 will significantly increase during the process of angiogenesis. Integrins will bind to the ECM and enhance cancer cell adhesion. Cancer cell adhesion will help cancer cells move to blood vessels that supply blood to cancer cells so that cancer cells can move to other organs suitable for growth.

Fig. 5.. OSs active ingredients inhibit cancer cells from proliferating and cause them to undergo apoptosis. Several active substances, including quercetin, eugenol, and rosmarinic acid, have been identified in OS Linn. Through the induction of cell death by an increase in ROS and NO, these bioactive substances will limit and shrink the growth of cancer cells. Bax, cytochrome C, caspase 3, caspase 9, and IL-1β all rise throughout the apoptotic process. Proliferating cell nuclear antigen (PCNA), glutathione S-transferase (GST-pi), and EGFR will all drop in response to a reduction in cancer cell proliferation. OS also inhibits metastasis, which is characterized by decreased expression of ECM (MMP-2, MMP-9), PI3K, glutathione peroxidase (GSH-Px), and catalase (CAT). It does this by reducing integrin αvβ3, integrin α5β1, and VEGF.