Sasanquasaponin inhibited epithelial to mesenchymal transition in prostate cancer by regulating the PI3K/Akt/mTOR and Smad pathways.

Abstract

CONTEXT:

Sasanquasaponin (SQS) is a commonly used traditional Chinese medicine proved to have a wide range of pharmacological functions.

OBJECTIVE:

The objective of this study is to explore the effect and underlying mechanism of SQS in the treatment of prostate cancer (PC).

MATERIALS AND METHODS:

PC cell lines (22Rv1 and PC-3) were treated with SQS (0, 0.5, 1, 2, and 4 μM) for 12 or 24 h. The viability of cells was evaluated, while the mRNA and protein levels of epithelial to mesenchymal transition (EMT)-related genes in PC cell lines were measured (Groups: Control, TGF-β1, TNF-α, TGF-β1 + TNF-α, and TGF-β1 + TNF-α + SQS). The migration and invasion abilities of PC cell lines were evaluated (Groups: Control, SQS). Finally, the antitumour effect of SQS (25, 50,100, and 200 mg/kg) in BALB/c nude mice (6 weeks, 18-20 g) was evaluated (Groups: Control, Vehicle, 25, 50,100, and 200 mg/kg SQS). The study duration was 1 month.

RESULTS:

SQS inhibited the viability and the number of colonies of 22Rv1 or PC-3 cells. The IC50 of SQS of 12 and 24 h in these two cells was 3.25, 1.82, 4.76, and 4.70 μM, respectively. SQS inhibited the adhesion, migration, and invasion of PC cells. It also inhibited the expression of EMT-related markers of PC cells. The PI3K/Akt/mTOR and Smad2/3 signalling pathways were activated in the process of EMT, and SQS could significantly reduce the activation of the PI3K/Akt/mTOR and Smad2/3 pathways. Finally, SQS inhibited the growth of xenograft tumours in vivo.

CONCLUSIONS:

SQS inhibited EMT in PC by regulating the PI3K/Akt/mTOR and Smad pathways.

• Authors: Wenfeng Li, Yuanshen Mao, Bao Hua, Xin Gu, Chao Lu, Bin Xu, Weixin Pan
• Journal: Pharmaceutical biology (Pharm Biol) Vol. 60 Issue 1 Pg. 1865-1875 (Dec 2022) ISSN: 1744-5116 [Electronic] England
• PMID: 36205544 (Publication Type: Journal Article)

Chemical References

• 22-O-angeloylcamelliagenin C-3-O-(glucopyranosyl-1-2)(glucopyranosyl-1-2-O-arabinopyranosyl-1-3-)glucopyranosiduronic acid
• RNA, Messenger
• Saponins
• Smad Proteins
• Transforming Growth Factor beta1
• Tumor Necrosis Factor-alpha
• MTOR protein, human
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Animals
• Cell Line, Tumor
• Cell Movement
• Epithelial-Mesenchymal Transition
• Humans
• Male
• Mice
• Mice, Nude
• Phosphatidylinositol 3-Kinases (metabolism)
• Prostatic Neoplasms (drug therapy)
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Messenger
• Saponins
• Smad Proteins (metabolism)
• TOR Serine-Threonine Kinases (metabolism)
• Transforming Growth Factor beta1 (metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)