Polysaccharopeptide enhanced the anti-cancer effect of gamma-tocotrienol through activation of AMPK.

Abstract

BACKGROUND:

Prostate cancer (PCa) frequently relapses after hormone ablation therapy. Unfortunately, once progressed to the castration resistant stage, the disease is regarded as incurable as prostate cancer cells are highly resistant to conventional chemotherapy.

METHOD:

We recently reported that the two natural compounds polysaccharopeptide (PSP) and Gamma-tocotrienols (γ-T3) possessed potent anti-cancer activities through targeting of CSCs. In the present study, using both prostate cancer cell line and xenograft models, we seek to investigate the therapeutic potential of combining γ-T3 and PSP in the treatment of prostate cancer.

RESULT:

We showed that in the presence of PSP, γ-T3 treatment induce a drastic activation of AMP-activated protein kinase (AMPK). This was accompanied with inactivation of acetyl-CoA carboxylase (ACC), as evidenced by the increased phosphorylation levels at Ser 79. In addition, PSP treatment also sensitized cancer cells toward γ-T3-induced cytotoxicity. Furthermore, we demonstrated for the first time that combination of PSP and γ-T3 treaments significantly reduced the growth of prostate tumor in vivo.

CONCLUSION:

Our results indicate that PSP and γ-T3 treaments may have synergistic anti-cancer effect in vitro and in vivo, which warrants further investigation as a potential combination therapy for the treatment of cancer.

• Authors: Ji Liu, Eunice Yuen-Ting Lau, Jiezhong Chen, Joan Yong, Kai Dun Tang, Jessica Lo, Irene Oi-Lin Ng, Terence Kin-Wah Lee, Ming-Tat Ling
• Journal: BMC complementary and alternative medicine (BMC Complement Altern Med) Vol. 14 Pg. 303 (Aug 16 2014) ISSN: 1472-6882 [Electronic] England
• PMID: 25129068 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Chromans
• Proteoglycans
• polysaccharide peptide
• Vitamin E
• plastochromanol 8
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (genetics, metabolism)
• Animals
• Antineoplastic Agents (administration & dosage)
• Cell Line
• Chromans (administration & dosage)
• Drug Synergism
• Enzyme Activation
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Phosphorylation (drug effects)
• Prostatic Neoplasms (drug therapy, enzymology, genetics)
• Proteoglycans (administration & dosage)
• Vitamin E (administration & dosage, analogs & derivatives)