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Phytomedicine. 2018 Dec 1;51:139-150. doi: 10.1016/j.phymed.2018.10.012. Epub 2018 Oct 10.

Afrocyclamin A, a triterpene saponin, induces apoptosis and autophagic cell death via the PI3K/Akt/mTOR pathway in human prostate cancer cells.

Author information

1
School of Pharmacy, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, Republic of Korea.
2
Department of Immunology, School of Medicine, Konkuk University, Chungju 27478, Republic of Korea.
3
Comparative Biomedicine Research Branch, Division of Translational Science, Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do 10408, Republic of Korea.
4
School of Pharmacy, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, Republic of Korea. Electronic address: jhkwak@skku.edu.
5
School of Pharmacy, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, Republic of Korea. Electronic address: hkims@skku.edu.

Abstract

BACKGROUND:

Afrocyclamin A, an oleanane-type triterpene saponin, was isolated from Androsace umbellata which used as a traditional herbal medicine.

PURPOSE:

This study aimed to explore the anticancer activity of afrocyclamin A on human prostate cancer cells in vitro as well as in vivo.

METHODS:

Cytotoxicity, cell cycle distribution, apoptosis, and autophagic cell death were measured following exposure to afrocyclamin A. In vivo antitumor activity of afrocyclamin A was assessed in a xenograft model. The protein levels of p-Akt, p-mTOR, Bax, Bcl-2, caspase-3, and caspase-9 were quantified using western blot analysis.

RESULTS:

In DU145 cells, afrocyclamin A increased cytotoxicity, caused changes in cell morphology, and induced sub-G0/G1 phase indicating increased apoptosis. Afrocyclamin A robustly induced autophagic cell death as demonstrated by the conversion of LC3B-I to LC3B-II, and the formation of autophagic vacuoles as revealed by western blot analysis and fluorescence staining, respectively. Afrocyclamin A also inhibited the phosphorylation of PI3K, Akt, and mTOR, suggesting their role in afrocyclamin A induced cell death. In addition, afrocyclamin A inhibited cell migration and invasion in concentration and time-dependent manners. In an in vivo xenograft model, afrocyclamin A inhibited the growth of DU145 cells.

CONCLUSION:

Afrocyclamin A has anticancer activity via the PI3K/Akt/mTOR pathway, which leads to cell death.

KEYWORDS:

Afrocyclamin A; Apoptosis; Autophagy; PI3K/Akt/mTOR; Triterpene saponin

PMID:
30466611
DOI:
10.1016/j.phymed.2018.10.012
[Indexed for MEDLINE]

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