α-Mangostin Induces Apoptosis and Inhibits Metastasis of Breast Cancer Cells via Regulating RXRα-AKT Signaling Pathway

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.

α‐Mangostin induces oxidative damage, mitochondrial dysfunction, and apoptosis in a triple‐negative breast cancer model

“…Moreover, our results agree with the results of Lee et al, (2017), who demonstrate that α‐M induces apoptosis through the activation of ROS and caspase 3 cleavage in cervical cancer cells. Also, our results agree with Zhu et al (2021) results, who demonstrate that in MDA‐MB‐231, a TNBC cancer cell model, α‐M induced apoptosis and avoided proliferation and migration by activating PI3K/Akt signaling pathway. α‐M also promoted BAX activation along with caspase 3 cleavage, which was demonstrated in MCF‐7, a breast cancer cell line that expresses the ER, where α‐M induced the overexpression of modulator of apoptosis 1, causing the activation of BAX and caspase 3 and later triggering apoptosis.…”

“…Due to the latter, chemotherapy is the only available therapy for TNBC, which could induce side effects and chemoresistance. α‐M has shown anticancer effects in different cancer models (Lee et al, 2016; Zhu et al, 2021), so this polyphenol could be a potential therapy for the treatment of TNBC. For example, Perez‐Rojas et al (2016) showed that α‐M induces apoptosis in a cervical cancer cell line.…”

α-Mangostin Exhibits a Therapeutic Effect on Spinal Cystic Echinococcosis by Affecting Glutamine Metabolism

“…α-mangostin (α-MG) is a representative natural xanthone isolated from the pericarps of mangosteen. It has been proven to possess a variety of pharmacological properties, such as anticarcinogenic, anti-inflammatory, antidiabetic, and antioxidant activities ( 13 , 14 ), as well as hepatoprotective, cardioprotective, and neuroprotective properties. Of these, its anticarcinogenic activity is the most promising ( 15 – 17 ).…”

Signaling Pathways and Natural Compounds in Triple-Negative Breast Cancer Cell Line

“…Another research reported that α-mangostin suppressed the proliferation, migration, and invasion of the PI3K/Akt signaling pathway by targeting RXRα and cyclin D1 in vitro and in silico studies. This compound was inhibited in the MDA-MB-231 cell line, with an IC 50 value of 11.37 µM [165].…”