2. Academic Validation
  3. Panaxynol, a natural Hsp90 inhibitor, effectively targets both lung cancer stem and non-stem cells

Panaxynol, a natural Hsp90 inhibitor, effectively targets both lung cancer stem and non-stem cells

  • Cancer Lett. 2018 Jan 1;412:297-307. doi: 10.1016/j.canlet.2017.10.013.
Huong Thuy Le 1,  Huy Truong Nguyen 2,  Hye-Young Min 3,  Seung Yeob Hyun 1,  Soonbum Kwon 2,  Yeongcheol Lee 2,  Thi Hong Van Le 4,  Jeeyeon Lee 2,  Jeong Hill Park 2,  Ho-Young Lee 5
Affiliations

Affiliations

  • 1 Creative Research Initiative Center for Concurrent Control of Emphysema and Lung Cancer, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea; College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
  • 2 College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
  • 3 Creative Research Initiative Center for Concurrent Control of Emphysema and Lung Cancer, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, and College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
  • 4 Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Viet Nam.
  • 5 Creative Research Initiative Center for Concurrent Control of Emphysema and Lung Cancer, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea; College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, and College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: hylee135@snu.ac.kr.
PMID: 29061506 DOI: 10.1016/j.canlet.2017.10.013
Abstract

Cancer stem-like cells (CSCs) contribute to tumor recurrence and chemoresistance. Hence, strategies targeting CSCs are crucial for effective Anticancer therapies. Here, we demonstrate the capacities of the non-saponin fraction of Panax ginseng and its active principle panaxynol to inhibit HSP90 function and viability of both non-CSC and CSC populations of NSCLC in vitro and in vivo. Panaxynol inhibited the sphere forming ability of NSCLC CSCs at nanomolar concentrations, and micromolar concentrations of panaxynol suppressed the viability of NSCLC cells (non-CSCs) and their sublines carrying acquired chemoresistance with minimal effect on normal cells derived from various organs. Orally administered panaxynol significantly reduced lung tumorigenesis in KrasG12D/+ transgenic mice and mice carrying NSCLC xenografts without detectable toxicity. Mechanistically, panaxynol disrupted HSP90 function by binding to the N-terminal and C-terminal ATP-binding pockets of HSP90 without increasing HSP70 expression. These data suggest the potential of panaxynol as a natural HSP90 Inhibitor targeting both the N-terminal and C-terminal of HSP90 with limited toxicities.

Keywords

Cancer stem cells; Heat shock protein; Lung cancer; Panaxynol.

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