Garcinol exerts anti-cancer effect in human cervical cancer cells through upregulation of T-cadherin.

Abstract

Garcinol, a polyisoprenylated benzophenone, has been demonstrated to exert anti-cancer effects in various tumor cells. However, the effect of garcinol on cervical cancer (CC) cell progression and the related molecular mechanism remains poorly understood. Accumulating evidence has verified that downregualtion of T-cadherin is closely associated with tumorigenesis, suggesting that T-cadherin might be a potential therapeutic target for cancer treatment. In the present study, Hela and SiHa cells were treated with different concentrations of garcinol (0, 5, 10, and 25 u M), and T-cadherin siRNA was synthesized and transfected into Hela and SiHa cells combined with garcinol (25 u M) treatment. We found that garcinol dose-dependently suppressed cell viability, colony formation, invasion, migration, cell cycle progression, and promoted cell apoptosis in CC cell lines, as well as inhibited tumor growth in xenograft model. Importantly, our results showed that garcinol treatment increased the expression of T-cadherin both in vitro and in vivo, and knockdown of T-cahderin partially reversed garcinol-induced inhibition of CC development via activating P13 K/AKT signaling pathway in CC cell lines. Thus, these findings demonstrated the tumor suppressive function of garcinol on CC progression, and emphasized that the T-cadherin/P13 K/AKT was a potential mechanism involved in the antumor effects of garcinol.

• Authors: Juan Zhao, Ting Yang, Jing Ji, Chen Li, Zhen Li, Long Li
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 107 Pg. 957-966 (Nov 2018) ISSN: 1950-6007 [Electronic] France
• PMID: 30257408 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Cadherins
• H-cadherin
• RNA, Small Interfering
• Terpenes
• garcinol

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacology)
• Apoptosis (drug effects)
• Cadherins (genetics)
• Cell Line, Tumor
• Disease Progression
• Dose-Response Relationship, Drug
• Female
• Gene Knockdown Techniques
• HeLa Cells
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• RNA, Small Interfering (genetics)
• Signal Transduction (drug effects)
• Terpenes (administration & dosage, pharmacology)
• Up-Regulation (drug effects)
• Uterine Cervical Neoplasms (drug therapy, genetics, pathology)
• Xenograft Model Antitumor Assays