F1012-2 inhibits the growth of triple negative breast cancer through induction of cell cycle arrest, apoptosis, and autophagy

Phytotherapy Research : PTR
Shasha TianHuajun Zhao

Abstract

Sesquiterpene lactones (SLs) are plant-derived constituents that have been proved to have potential antitumour activity. However, the intracellular molecular targets of SLs and the underlying molecular mechanisms have not been well elucidated. Here, we report that F1012-2, a novel SL active fraction, isolated from Eupatorium lindleyanum DC., can significantly inhibit the growth of triple-negative breast cancer (TNBC) cells (MDA-MB-231 and MDA-MB-468) but has no obvious inhibitory effect on the growth of human mammary epithelial cells (MCF-10A). The related mechanisms on cell growth inhibition of F1012-2 were demonstrated by inducing apoptosis in a caspase-dependent manner through the intrinsic pathway and extrinsic pathway. F1012-2 could also activate autophagy in TNBC cells. Simultaneously, we found that F1012-2-induced apoptosis was enhanced by inhibition of autophagy. Furthermore, F1012-2 could induce cell cycle arrest at G2/M phase with decreasing expression of cyclin B1, cdc2, and upregulating p21, p-cdc2. Also, F1012-2 activated Akt and p38 signalling pathways. In vivo, F1012-2 exhibited a potential antitumour effect in MDA-MB-231 xenografts without apparent toxicity. Taken together, our results identified that F1012-2 in...Continue Reading

References

May 23, 1998·Annual Review of Pharmacology and Toxicology·M HeinrichE Rodriguez
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·S A InnocenteJ M Lee
Oct 26, 1999·International Journal of Urology : Official Journal of the Japanese Urological Association·T KajiwaraK Kawabe
Nov 28, 2000·Expert Opinion on Investigational Drugs·G M Cragg, D J Newman
Apr 30, 2003·Cell Death and Differentiation·M Oren
Nov 25, 2003·Oncogene·Alexei DegterevJunying Yuan
Nov 25, 2003·Oncogene·Suzanne CoryJerry M Adams
May 6, 2004·The Journal of Clinical Endocrinology and Metabolism·K KaczirekB Niederle
Aug 25, 2004·The International Journal of Biochemistry & Cell Biology·Isei TanidaEiki Kominami
Dec 29, 2004·Journal of Natural Products·Mark S Butler
Jul 5, 2005·Current Medicinal Chemistry. Anti-cancer Agents·Siyuan ZhangHan-Ming Shen
Sep 9, 2005·Nature Reviews. Cancer·Yasuko KondoSeiji Kondo
Oct 13, 2006·Annual Review of Pharmacology and Toxicology·Sten OrreniusBoris Zhivotovsky
Feb 24, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Constantin TamvakopoulosPanayotis Pantazis
Apr 25, 2007·Apoptosis : an International Journal on Programmed Cell Death·Michal SchwarzAtan Gross
Nov 15, 2007·Cell Cycle·Thomas A Khavari, John Rinn
Feb 6, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Cornelia LiedtkeLajos Pusztai
Dec 3, 2008·International Journal of Cancer. Journal International Du Cancer·Min ZhangC D'Arcy J Holman
Mar 12, 2009·Anti-cancer Agents in Medicinal Chemistry·S Brøgger ChristensenJohn T Isaacs
Nov 12, 2010·The New England Journal of Medicine·William D FoulkesJorge S Reis-Filho
Feb 10, 2011·The Oncologist·Clifford A Hudis, Luca Gianni
Feb 12, 2011·Cell Death and Differentiation·R KangD Tang
Feb 23, 2011·Development, Growth & Differentiation·Masayuki Miura
Jun 5, 2012·Cold Spring Harbor Perspectives in Biology·Gautam DasEric H Baehrecke
Jan 30, 2013·Pharmacology & Therapeutics·Santiago Diaz-MoralliMarta Cascante
Jan 30, 2013·Breast Cancer Research and Treatment·Soley Bayraktar, Stefan Glück
Jun 21, 2013·International Journal of Molecular Sciences·Martin ChadwickCarol Wagstaff
Dec 7, 2013·Cellular Signalling·Laurence A BoothPaul Dent
May 2, 2014·Frontiers in Oncology·Camillo PortaAlessandra Mosca
Jul 12, 2014·BioMed Research International·Mónika Lippai, Péter Lőw
May 11, 2015·Apoptosis : an International Journal on Programmed Cell Death·Meenakshi TiwariShail K Chaube
Jun 25, 2016·Seminars in Nephrology·Steven C Borkan

❮ Previous
Next ❯

Citations

Aug 23, 2019·Phytotherapy Research : PTR·Ester Pagano, Angelo A Izzo
Oct 12, 2018·Medicinal Research Reviews·Hendrik FolkertsValerie R Wiersma
Nov 21, 2020·Neoplasia : an International Journal for Oncology Research·Zhihui ZhuHuajun Zhao
May 18, 2021·Chemistry & Biodiversity·Han ChenXiaoling Lu
Jun 21, 2020·Anti-cancer Agents in Medicinal Chemistry·Milad AshrafizadehAmirhossein Sahebkar

❮ Previous
Next ❯

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

Breast Cancer Triple-N

Breast cancer cells have receptors for estrogen, progesterone, HER2 receptors (also called ERBB2). Triple-negative breast cancers do not have any of these receptors. Here are the latest discoveries pertaining to triple-negative breast cancers.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms