New metformin derivative HL156A prevents oral cancer progression by inhibiting the insulin-like growth factor/AKT/mammalian target of rapamycin pathways

Cancer Science
Thuy Giang LamSang-Gun Ahn

Abstract

Metformin is a biguanide widely prescribed as an antidiabetic drug for type 2 diabetes mellitus patients. The purpose of the present study was to observe the effects of the new metformin derivative, HL156A, on human oral cancer cell and to investigate its possible mechanisms. It was observed that HL156A significantly decreased FaDu and YD-10B cell viability and colony formation in a dose-dependent way. HL156A also markedly reduced wound closure and migration of FaDu and YD-10B cells. We observed that HL156A decreased mitochondrial membrane potential and induced reactive oxygen species (ROS) levels and apoptotic cells with caspase-3 and -9 activation. HL156A inhibited the expression and activation of insulin-like growth factor (IGF)-1 and its downstream proteins, AKT, mammalian target of rapamycin (mTOR), and ERK1/2. In addition, HL156A activated AMP-activated protein kinase/nuclear factor kappa B (AMPK-NF-κB) signaling of FaDu and YD-10B cells. A xenograft mouse model further showed that HL156A suppressed AT84 mouse oral tumor growth, accompanied by down-regulated p-IGF-1, p-mTOR, proliferating cell nuclear antigen (PCNA) and promoted p-AMPK and TUNEL expression. These results suggest the potential value of the new metformin de...Continue Reading

References

Aug 19, 2000·Cellular and Molecular Life Sciences : CMLS·N JohanssonV M Kähäri
May 29, 2002·Pathology International·Kazuki NabeshimaTetsuro Sameshima
Apr 20, 2004·Cancer Cell·Li MaoVassiliki A Papadimitrakopoulou
Jun 9, 2004·International Journal of Cancer. Journal International Du Cancer·Colin HopperGraham Putnam
Jul 13, 2006·Expert Review of Anticancer Therapy·David ChinWilliam B Coman
Mar 18, 2008·Critical Reviews in Oncology/hematology·Sirwan M HadadAlastair M Thompson
Nov 20, 2010·The FEBS Journal·Chrisostomi GialeliNikos K Karamanos
Dec 29, 2011·Oncotarget·Sonia Del BarcoJavier A Menendez
May 23, 2012·Prostate Cancer and Prostatic Diseases·A J ColquhounV Venkateswaran
Jul 17, 2013·Experimental Biology and Medicine·Chih-Hao WangYau-Huei Wei
Oct 17, 2013·Carcinogenesis·Tunde AkinyekeXin Li
Dec 18, 2013·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·S M HadadA M Thompson
Apr 1, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alastair M Thompson
Sep 12, 2015·Expert Opinion on Drug Safety·Nicoletta ProvincialiAndrea DeCensi
Jul 1, 2016·Pharmacological Reports : PR·Stanisław SośnickiLudmiła Węglarz
Oct 21, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Marie DauganVincent Boudy
Nov 30, 2016·Cancer Metastasis Reviews·Angel Guerrero-ZotanoCarlos L Arteaga

❮ Previous
Next ❯

Citations

Aug 17, 2019·International Journal of Molecular Sciences·Yi-Ta HsiehWan-Chun Li
May 10, 2020·International Journal of Molecular Sciences·Choudhary HarshaAjaikumar B Kunnumakkara
Feb 6, 2020·Current Opinion in Otolaryngology & Head and Neck Surgery·Isabel VilasecaFrancesc-Xavier Avilés-Jurado
Oct 27, 2020·Journal of Medicinal Chemistry·Yibin XuNouri Neamati

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
flow cytometry
Assay
fluorescence microscopy

Related Concepts

Related Feeds

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.