Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Medicago orbicularis Has Antioxidant, Antihemolytic, and Anti-cancerous Activities and Augments Cisplatin-Induced Cytotoxicity in A549 Lung Cancer Cells

Version 1 : Received: 16 September 2023 / Approved: 18 September 2023 / Online: 19 September 2023 (03:23:46 CEST)

A peer-reviewed article of this Preprint also exists.

Shaito, A.A.; Omairi, I.; Al-Thani, N.; Seglab, F.; Ad-Darwish, E.; Kobeissy, F.; Nasreddine, S. Determination of Medicago orbicularis Antioxidant, Antihemolytic, and Anti-Cancerous Activities and Its Augmentation of Cisplatin-Induced Cytotoxicity in A549 Lung Cancer Cells. Plants 2024, 13, 442. Shaito, A.A.; Omairi, I.; Al-Thani, N.; Seglab, F.; Ad-Darwish, E.; Kobeissy, F.; Nasreddine, S. Determination of Medicago orbicularis Antioxidant, Antihemolytic, and Anti-Cancerous Activities and Its Augmentation of Cisplatin-Induced Cytotoxicity in A549 Lung Cancer Cells. Plants 2024, 13, 442.

Abstract

Cancer is second leading cause of death, worldwide. Lung cancer is the leading cause of cancer-related mortality. Plant-based therapeutics and herbal medicine have played a vital role in the development of several anti-cancerous agents, and has been used to reduce the severe side effects of chemotherapy as well. Since the anti-lung cancer properties of the plant Medicago. orbicularis are not explored yet, we identified its phytochemical composition and investigated the anti-oxidant, anti-hemolytic, and anti-cancerous properties of extracts of this plant in A549 human lung adenocarcinoma cells. Results show that all parts of M. orbicularis (stems, leaves, and fruits) exhibit remarkable anti-oxidant and hemolytic activities. In addition, all extracts showed a dose-dependent anti-cancerous cytotoxic activity against A549 cells; with fruit extracts being the most potent. This cytotoxic effect could be related, at least partly, to the induction of apoptosis, where M. orbicularis fruit extracts activated Caspase-3 and PARPP-1, and reduced the ratio of anti-apoptotic BCL-2/ pro-apoptotic BAX, thereby promoting cellular death. Furthermore, the use of M. orbicularis, in combination with a conventional chemotherapeutic agent, cisplatin, was assessed. Indeed, combination of cisplatin and M. orbicularis fruit extracts was more cytotoxic and induced more aggregation of A549 cells than either treatment alone. GC-MS analysis and total polyphenol and flavonoid content determination indicated that M. orbicularis is rich in compounds that have anti-cancerous effects. M. orbicularis may be a potential source of anti-cancerous agents to manage progression of lung cancer and its resistance to therapy.

Keywords

Medicago orbicularis; Lung cancer; Herbal medicine; Antioxidants; hemolytic; cisplatin; A549 cells

Subject

Medicine and Pharmacology, Complementary and Alternative Medicine

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