Phyto-Phospholipid Conjugated Scorpion Venom Nanovesicles as Promising Carrier That Improves Efficacy of Thymoquinone against Adenocarcinoma Human Alveolar Basal Epithelial Cells

Hani Z Asfour,Usama A Fahmy,Ulfat M Omar,Ahmed A Aldarmahi,Alshaimaa M Almehmady,Waleed S Alharbi,Alaa Bagalagel,Osama A A Ahmed,Shadi A Zakai,Abdulmohsin J Alamoudi,Singkome Tima,Reem Diri,Rasha A Mansouri,Nabil A Alhakamy

doi:10.3390/pharmaceutics13122144

Abstract

Lung cancer is a dangerous type of cancer in men and the third leading cause of cancer-related death in women, behind breast and colorectal cancers. Thymoquinone (THQ), a main compound in black seed essential oils, has a variety of beneficial effects, including antiproliferative, anti-inflammatory, and antioxidant properties. On the other hand, scorpion venom peptides (SV) induce apoptosis in the cancer cells, making it a promising anticancer agent. THQ, SV, and Phospholipon® 90H (PL) were incorporated in a nano-based delivery platform to assess THQ’s cellular uptake and antiproliferative efficacy against a lung cancer cell line derived from human alveolar epithelial cells (A549). Several nanovesicles were prepared and optimized using factorial experimental design. The optimized phytosome formulation contained 79.0 mg of PL and 170.0 mg of SV, with vesicle size and zeta potential of 209.9 nm and 21.1 mV, respectively. The IC50 values revealed that A549 cells were significantly more sensitive to the THQ formula than the plain formula and THQ. Cell cycle analysis revealed that THQ formula treatment resulted in significant cell cycle arrest at the S phase, increasing cell population in this phase by 22.1%. Furthermore, the THQ formula greatly increased cell apoptosis (25.17%) when compared to the untreated control (1.76%), plain formula (11.96%), or THQ alone (13.18%). The results also indicated that treatment with THQ formula significantly increased caspase-3, Bax, Bcl-2, and p53 mRNA expression compared to plain formula and THQ. In terms of the inflammatory markers, THQ formula significantly reduced the activity of TNF-α and NF-κB in comparison with the plain formula and THQ only. Overall, the findings from the study proved that a phytosome formulation of THQ could be a promising therapeutic approach for the treatment of lung adenocarcinoma.

Highlights

IntroductionSmall-cell carcinoma and non-small-cell carcinoma are the two subtypes
Lung cancer is one of the most serious types of cancer
The novel THQ formula developed in this study showed significant cytotoxicity against the A549 lung cancer cells

Summary

Introduction

Small-cell carcinoma and non-small-cell carcinoma are the two subtypes. Lung adenocarcinoma is the most common type of lung cancer. It is an example of a non-small-cell lung cancer (NSCLC) with a significant relation to smoking, which continues to be the leading cause of lung cancer. There are other risk factors that lead to lung cancer, such as diet, alcohol, and air pollution [4]. There are various types of lung cancer based on the histology, such as squamous cell carcinoma and bronchioalveolar cell carcinoma [4]. Patients with lung cancer may receive different therapeutic options according to the stage of the disease, including surgery, radiation, chemotherapy, targeted therapy, and immunotherapy. Prolonged use of targeted treatments leads to the development of acquired resistance, and reducing their efficacy [5]

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Discussion

Conclusion