Ginsenoside Rp1, A Ginsenoside Derivative, Augments Anti-Cancer Effects of Actinomycin D via Downregulation of an AKT-SIRT1 Pathway

Cancers
Un-Jung YunYong-Nyun Kim

Abstract

Novel strategies for overcoming multidrug resistance are urgently needed to improve chemotherapy success and reduce side effects. Ginsenosides, the main active components of Panax ginseng, display anti-cancer properties and reverse drug resistance; however, the biological pathways mediating this phenomenon remain incompletely understood. This study aimed to evaluate the anti-cancer effects of ginsenoside Rp1, actinomycin D (ActD), and their co-administration in drug-resistant cells and murine xenograft model of colon cancer, and explore the underlying mechanisms. ActD increased expression and activity of SIRT1 in drug-resistant LS513 colon cancer, OVCAR8-DXR ovarian cancer, and A549-DXR lung cancer cells, but not in ActD-sensitive SW620 colon cancer cells. Inhibition of SIRT1, either pharmacologically, with EX527 or through siRNA, stimulated p53 acetylation and apoptosis in LS513 cells when treated with ActD. ActD also increased AKT activation in drug-resistant cells. Inhibition of AKT abrogated ActD-induced upregulation of SIRT1, suggesting that the AKT-SIRT1 pathway is important in ActD resistance. Rp1 inhibited both ActD-induced AKT activation and SIRT1 upregulation and re-sensitized the cells to ActD. Synergistic antitumor ...Continue Reading

References

Oct 1, 1970·Journal of Cellular Physiology·R P Perry, D E Kelley
Mar 21, 2002·Nature Reviews. Cancer·Michael M GottesmanSusan E Bates
Jan 18, 2003·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Kip A WestPhillip A Dennis
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Hwei-Ling ChengKatrin F Chua
Dec 23, 2004·The Journal of Biological Chemistry·Hannah Elisabeth MischoSuisheng Zhang
Mar 28, 2008·Archives of Pharmacal Research·Hyog-Young KwonDong-Kwon Rhee
Jun 25, 2008·Biochemical and Biophysical Research Communications·Keitaro KojimaMasafumi Ito
Aug 30, 2008·Molecular Cancer Research : MCR·Xing-Jie LiangMichael M Gottesman
Aug 30, 2008·The American Journal of Surgical Pathology·Kyu Yun JangWoo Sung Moon
Jul 16, 2009·Current Vascular Pharmacology·Jian-Ming LüChangyi Chen
Sep 11, 2013·Genes & Cancer·Zhiqiang Wang, Wenyong Chen
Mar 18, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Thomas T VellingaOnno Kranenburg
May 23, 2015·OncoTargets and Therapy·Chong LiChangping Wu
Jan 19, 2017·International Journal of Molecular Medicine·Mengyao SunHong Zhang
Jul 2, 2017·Translational Oncology·David Hamisi MvuntaTanri Shiozawa
Oct 27, 2017·Advanced Pharmaceutical Bulletin·Behzad MansooriBehzad Baradaran
Nov 14, 2017·Journal of Cellular Biochemistry·Bing-Gang ZhouHuan-Min Gao
May 3, 2019·Cell Death & Disease·Neelum Aziz YousafzaiXian Wang
Jul 3, 2019·International Journal of Molecular Sciences·Débora Kristina Alves-Fernandes, Miriam Galvonas Jasiulionis

❮ Previous
Next ❯

Citations

Dec 5, 2020·Journal of Ethnopharmacology·Tingting LouXiangyan Li
Apr 27, 2021·Molecular and Cellular Biochemistry·Do Luong HuynhCuong Thach Nguyen
Aug 28, 2021·International Journal of Molecular Sciences·Alexandra KissCsaba Hegedűs

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
acetylation
xenografts
Transfection
protein
Protein Assay
flow cytometry

Software Mentioned

CellQuest

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.