Abstract
Mangostin, which has the function of anti-inflammatory, antioxidant, and anticancer, etc, is one of the main active ingredients of the hull of the mangosteen. The main objective of the study was to elucidate its anti-cancer function and possible mechanism. α-Mangostin was separated and structurally confirmed. MTT method was used to check the effect of mangostin on breast cancer cell proliferation. Then the effect of α-Mangostin on the transcriptional activity of RXRα was tested by dual-luciferase reporter gene assay. And Western blot (WB) was used to detect the expression of apoptosis-related proteins or cell cycle-associated proteins after treatment. Also, this study was to observe the effects of α-Mangostin on the invasion of breast cancer cell line MDA-MB-231. α-Mangostin regulates the downstream effectors of the PI3K/AKT signaling pathway by degrading RXRα/tRXRα. α-Mangostin can trigger PARP cleavage and induce apoptosis, which may be related to the induction of upregulated BAX expression and downregulation of BAD and cleaved caspase-3 expression in MDA-MB-231 cells through blockade of AKT signaling. The experiments verify that α-Mangostin have evident inhibition effects of invasion and metastasis of MDA-MB-231 cells. Cyclin D1 was involved in the anticancer effects of α-Mangostin on the cell cycle in MDA-MB-231 cells. α-Mangostin induces apoptosis, suppresses the migration and invasion of breast cancer cells through the PI3K/AKT signaling pathway by targeting RXRα, and cyclin D1 has involved in this process.
Highlights
Mangostin is a series of natural compounds isolated from the epicarp of the fruits of Garcinia Mangostana Linn which is one of the most popular herbal medicines (Nguyen et al, 2020)
The antitumor activity of α-Mangostin has been demonstrated in numerous studies (Asasutjarit et al, 2019; Ittiudomrak et al, FIGURE 6 | α-mangostin suppressed the migration and invasion of triple negative breast cancer (TNBC) Cells in Vitro. (A) The cell migration ability was determined by wound healing assay. (B) The cell migration and invasion were determined by Transwell assay. (C) The expression levels of Mmp2 and Mmp9 were determined by western blotting analysis in MDA-MB-231 cells after α-Mangostin treatment
Apoptosis of breast cancer cells induced by α-Mangostin has been reported (Lee et al, 2010; Mardianingrum et al, 2020), but its specific molecular mechanism remains unclear
Summary
Mangostin is a series of natural compounds isolated from the epicarp of the fruits of Garcinia Mangostana Linn which is one of the most popular herbal medicines (Nguyen et al, 2020). The cytotoxicity of more than 10 types of compounds extracted from the epicarp of the mangosteen fruit has been tested, of which α-Mangostin was the most toxic to human leukemia cell lines (Jasek et al, 2014; Austin et al, 2015). The toxicity of methanol extracts from mangosteen shells on human breast cancer SKBR3 cells was confirmed (Scolamiero et al, 2018; Bissoli and Muscari, 2020), and the authors speculated that the active ingredient causes apoptosis by inhibiting low-density lipoprotein (LDL) oxidation and acid sheath phospholipase activity
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