Anticancer effects of Aegle marmelos leaves extract on nude mice bearing lung cancer A549 cell subsets SP and NSP cells and its effect on tumor size and weight
Aegle marmelos
Aegle marmelos Correa commonly known as Bilva or Sriphal or Shivadruma (the tree of shiva) in Sanskrit, Bel or Bael in Hindi, and as wood apple, stone apple, Bengal quince, Indian quince, holy fruit or golden apple in English, is an important medicinal tree in India. Bael trees are indigenous to India and are found growing in abundance in the Himalayan regions, Bengal, Central and South India, as well as in Srilanka, Burma, Thailand, Bangladesh, Nepal, Vietnam, Laos, Cambodia, and Pakistan. Bael leaves are offered to the Indian deity, Lord Shiva, and the tree is planted extensively in temples for this reason (Das and Das, 1995; Maity et al., 2009).
Bael is reported to contain biologically important phytochemicals such as the volatile compounds limonene, β-phellandrene, p-cymene, linalool, α-cubebene, cineole, p-cymene, citronella, citral, β-cubebene, β-caryophyllene, α-humulene, caryophyllene oxide, humulene oxide, and hexadecanoic acid and coumarins such as aegeline, aegelenine, marmelin, furocoumarins, psoralen, o-isopentenyl halfordinol, and marmelosin. They also contain tartaric acid, linoleic acid, tannins, phlobatannins, flavon-3-ols, leucoanthocyanins, anthocyanins, and the flavonoid glycosides (Das and Das, 1995; Maity et al., 2009).
Aegle marmelos commonly known as bilwa or bael is an important medicinal plant in Ayurveda (Figure 41.1). The English name for bael is stone apple, as its rather large fruit is like pale yellow to golden orange when ripe. In Sanskrit, it is called bilva or sriphal or shivadruma (the tree of shiva), while in Hindi, it is referred to as bel or bael or sripal (Kritikar and Basu, 1984). It is the only plant belonging to the genus Aegle and belongs to the Rutaceae family. It is a slow-growing, spinous, tough subtropical tree and is found wildly throughout India, Ceylon, Burma, Thailand, and Indochina (Kritikar and Basu 1984).
The aim of the present study was to investigate the mechanism of the inhibitory effects of Aegle marmelos leaves extracts on nude mice with lung cancer A549 cell subsets side population (SP) and non‑SP (NSP) cells. BALB/c mice were orally dosed with the tumor cells of A549 SP or NSP subsets consisting of 1x109 cells/l . After 16 days of inoculation with A549, the mice were orally dosed with curcumin (300 mg/kg) twice every day. A series of assays were performed to detect the effects of Aegle marmelos leaves extracts on: i) Tumor weight and size; ii) Notch and hypoxia inducible factor 1 (HIF‑1) mRNA expression by quantitative polymerase chain reaction; and iii) vascular endothelial growth factor (VEGF) and nuclear factor‑κB (NF‑κB) by immunohistochemistry. It was determined that curcumin decreased the tumor weight and size, downregulated the expression of Notch and HIF‑1 mRNA and suppressed the VEGF and NF‑κB expression. These results indicated that Aegle marmelos leaves extract inhibits lung cancer growth through the regulation of angiogenesis mediated by VEGF signalin
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