Silibinin-induced endoplasmic reticulum stress and mitochondrial dysfunction suppress growth of endometriotic lesions

Journal of Cellular Physiology
Jiyeon HamGwonhwa Song

Abstract

Silibinin is a flavonolignan extracted from milk thistle, which has been used for treating liver disorders, various cancers, and gynecological diseases. However, attempts for treating endometriosis with silibinin are lacking. In this study, we observed that silibinin exerts antiproliferative and apoptotic effects on human endometriotic cell lines VK2/E6E7 and End1/E6E7. We also identified that silibinin-induced oxidative stress and lipid peroxidation in human endometriotic cells. Moreover, we observed upregulation of calcium concentration in the cytosol and mitochondrial matrix, which resulted in mitochondrial dysfunction. Furthermore, induction of endoplasmic reticulum stress signals with rapid mitogen-activated protein kinase (MAPK) pathway signaling resulted in apoptosis of both cells. Using an animal model mimicking the retrograde menstruation hypothesis, we verified the effects of silibinin on reducing endometriotic lesions by inhibiting the expression of inflammatory cytokines in mice. Silibinin might be used as a novel therapeutic agent or supplement for inhibiting progression of endometriosis in vitro and in vivo.

References

May 1, 1996·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·G ScambiaS Mancuso
Oct 6, 2000·Fertility and Sterility·E M TuckermanS M Laird
Nov 16, 2004·Lancet·Linda C Giudice, Lee C Kao
Oct 4, 2005·The Journal of Clinical Investigation·Chunyan XuJohn C Reed
Dec 13, 2005·Journal of Minimally Invasive Gynecology·Michele VignaliMauro Busacca
Aug 8, 2006·American Journal of Obstetrics and Gynecology·Mauro BusaccaFabio Parazzini
Aug 16, 2008·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Meisong LuYan Xu
Oct 17, 2009·The Journal of Steroid Biochemistry and Molecular Biology·Jürgen Geisler, Per E Lønning
Mar 25, 2010·Archives of Gynecology and Obstetrics·Ebru ZulfikarogluSertac Batioglu
Jul 31, 2012·Biochemical and Biophysical Research Communications·Yun Ho ChoiGuang Hai Yan
Nov 28, 2012·Obstetrics and Gynecology Clinics of North America·Matthew Latham Macer, Hugh S Taylor
Jun 14, 2013·Proceedings of the National Academy of Sciences of the United States of America·George S B WilliamsW J Lederer
Jul 16, 2013·Biochimica Et Biophysica Acta·Renata Sano, John C Reed
Jul 25, 2013·Cancer Letters·David Sadava, Susan E Kane
Nov 8, 2013·Breast Cancer Research and Treatment·Lisa GallicchioKathy J Helzlsouer
Dec 3, 2013·Natural Product Reports·Hemant KumarDong-Kug Choi
Dec 25, 2013·Nature Reviews. Endocrinology·Paolo VercelliniLuigi Fedele
Jan 30, 2014·The Journal of Pharmacology and Experimental Therapeutics·Thae Hyun KimKi Hyung Kim
Mar 22, 2014·BMJ : British Medical Journal·Martha HickeyCindy Farquhar
Apr 18, 2014·Annals of the New York Academy of Sciences·Simone FerreroUmberto Leone Roberti Maggiore
May 9, 2014·Gynecologic Oncology·Chao GaoFengxia Xue
Dec 9, 2014·Women's Health·Milena KrálíčkováVaclav Vetvicka
Mar 26, 2015·Methods in Molecular Biology·Aditya DandekarKezhong Zhang
Apr 25, 2015·Nature Reviews. Cancer·Cynthia X MaMatthew J Ellis
May 23, 2015·Biochemical and Biophysical Research Communications·Sten OrreniusBoris Zhivotovsky
May 23, 2015·Biochemical and Biophysical Research Communications·Joachim KrebsMarek Michalak
Aug 19, 2015·Frontiers in Oncology·Yoon-Hee HongYong Sang Song
Aug 22, 2015·Redox Biology·Agnes GörlachOlga Krizanova
Sep 8, 2015·Women's Health·Umit Inceboz
Sep 24, 2015·Women's Health·Mehtap PolatHakan Yaralı
Oct 21, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Majid MomenySeyed H Ghaffari
Jan 1, 2014·SAGE Open Medicine·Abed AgbaryaJamal Mahajna
Jul 16, 2016·Biomedit︠s︡inskai︠a︡ khimii︠a︡·I B Zavodnik
Nov 11, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Michal Bijak

❮ 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

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.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.