Format

Send to

Choose Destination
Biomed Pharmacother. 2017 Aug;92:672-680. doi: 10.1016/j.biopha.2017.05.129. Epub 2017 Jun 3.

α-Mangostin inhibits DMBA/TPA-induced skin cancer through inhibiting inflammation and promoting autophagy and apoptosis by regulating PI3K/Akt/mTOR signaling pathway in mice.

Author information

1
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
2
Department of Clinical Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
3
Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, 226001, China.
4
Department of Dermatological, Armed Police Hospital of Shanghai, Shanghai 201103, China.
5
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China. Electronic address: 18795719287@163.com.

Abstract

Skin cancer is the most common form of cancer responsible for considerable morbidity and mortality, the treatment progress of which remains slow though. Therefore, studies identifying anti-skin cancer agents that are innocuous are urgently needed. α-Mangostin, a natural product isolated from the pericarp of mangosteen fruit, has potent anti-cancer activity. However, its role in skin cancer remains unclear. The aim of this study was to evaluate the treatment effect of α-mangostin on skin tumorigenesis induced by 9,10-dimethylbenz[a]anthracene (DMBA)/TPA in mice and the potential mechanism. Treatment with α-mangostin significantly suppressed tumor formation and growth, and markedly reduced the incidence rate. α-Mangostin not only inhibited the expressions of pro-inflammatory factors, but also promoted the production of anti-inflammatory factors in tumor and blood. It induced autophagy of skin tumor and regulated the expressions of autophagy-related proteins. The protein expressions of LC3, LC3-II and Beclin1 increased whereas those of LC3-I and p62 decreased after treatment with α-mangostin. Moreover, α-mangostin promoted the apoptosis of skin tumor dose-dependently by up-regulating of Bax, cleaved caspase-3, cleaved PARP and Bad, and down-regulating of Bcl-2 and Bcl-xl. Furthermore, showed α-mangostin inhibited the PI3K/AKT/mTOR (mammalian target of rapamycin) signaling pathway, as evidenced by decreased expressions of phospho-PI3K (p-PI3K), p-Akt and p-mTOR, but did not affect the expressions of t-PI3K, t-Akt or t-mTOR. Collectively, α-mangostin suppressed murine skin tumorigenesis induced by DMBA/TPA through inhibiting inflammation and promoting autophagy and apoptosis by regulating the PI3K/Akt/mTOR signaling pathway, as a potential candidate for future clinical therapy.

KEYWORDS:

Apoptosis; Autophagy; DMBA/TPA; Inflammation; PI3K/Akt/mTOR; Skin tumorigenesis; α-Mangostin

PMID:
28582759
DOI:
10.1016/j.biopha.2017.05.129
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center