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Melatonin induces apoptotic death in LNCaP cells via p38 and JNK pathways: therapeutic implications for prostate cancer.
J Pineal Res. 2009 Aug; 47(1):8-14.JP

Abstract

Apoptosis, a form of cell death, is a fundamental process for the development and maintenance of multicellular organisms that promotes the removal of damaged, senescent or unwanted cells. Induction of cancer cell apoptosis is an important strategy of anticancer therapy. In this study, we examined if melatonin, the main secretory product of the pineal gland, inhibited the growth of prostate cancer cells (LNCaP) and promoted apoptosis via mitogen-activated protein kinases (MAPKs), which are closely associated with apoptosis and survival. Melatonin treatment significantly inhibited the growth of LNCaP cells in a dose- and time-dependent manner. It clearly induced both an early stage of apoptosis (propidium iodide(-), FITC Annexin-V(+)) and a late apoptosis/secondary necrosis (propidium iodide(+) and FITC Annexin-V(+)), which indicated induction of serial stages of apoptosis in cells. Moreover, melatonin markedly activated c-JUN N-terminal kinase (JNK) and p38 kinase, whereas extracellular signal-regulated kinase (ERK) was not responsive to melatonin. Treatment with MAPK inhibitors, PD98059 (ERK inhibitor), SP600125 (JNK inhibitor) and SB202190 (p38 inhibitor), confirmed that melatonin-induced apoptosis was JNK- and p38-dependent, but ERK-independent. In the presence of PD98059, caspase-3 activity increased, while levels of Bax/cytochrome c (Cyt c) and Bcl-2 decreased. These effects were opposite to those observed with SP600125 and SB202190 treatments. Together, these results strongly suggest that JNK and p38 activation directly participate in apoptosis induced by melatonin. Thus, melatonin may be of promise for anti-prostate cancer strategies.

Authors+Show Affiliations

Research Institute of Veterinary Medicine, Chungbuk National University, Chungbuk, Korea.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19522739

Citation

Joo, Seong Soo, and Yeong-Min Yoo. "Melatonin Induces Apoptotic Death in LNCaP Cells Via P38 and JNK Pathways: Therapeutic Implications for Prostate Cancer." Journal of Pineal Research, vol. 47, no. 1, 2009, pp. 8-14.
Joo SS, Yoo YM. Melatonin induces apoptotic death in LNCaP cells via p38 and JNK pathways: therapeutic implications for prostate cancer. J Pineal Res. 2009;47(1):8-14.
Joo, S. S., & Yoo, Y. M. (2009). Melatonin induces apoptotic death in LNCaP cells via p38 and JNK pathways: therapeutic implications for prostate cancer. Journal of Pineal Research, 47(1), 8-14. https://doi.org/10.1111/j.1600-079X.2009.00682.x
Joo SS, Yoo YM. Melatonin Induces Apoptotic Death in LNCaP Cells Via P38 and JNK Pathways: Therapeutic Implications for Prostate Cancer. J Pineal Res. 2009;47(1):8-14. PubMed PMID: 19522739.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Melatonin induces apoptotic death in LNCaP cells via p38 and JNK pathways: therapeutic implications for prostate cancer. AU - Joo,Seong Soo, AU - Yoo,Yeong-Min, Y1 - 2009/06/10/ PY - 2009/6/16/entrez PY - 2009/6/16/pubmed PY - 2009/9/4/medline SP - 8 EP - 14 JF - Journal of pineal research JO - J Pineal Res VL - 47 IS - 1 N2 - Apoptosis, a form of cell death, is a fundamental process for the development and maintenance of multicellular organisms that promotes the removal of damaged, senescent or unwanted cells. Induction of cancer cell apoptosis is an important strategy of anticancer therapy. In this study, we examined if melatonin, the main secretory product of the pineal gland, inhibited the growth of prostate cancer cells (LNCaP) and promoted apoptosis via mitogen-activated protein kinases (MAPKs), which are closely associated with apoptosis and survival. Melatonin treatment significantly inhibited the growth of LNCaP cells in a dose- and time-dependent manner. It clearly induced both an early stage of apoptosis (propidium iodide(-), FITC Annexin-V(+)) and a late apoptosis/secondary necrosis (propidium iodide(+) and FITC Annexin-V(+)), which indicated induction of serial stages of apoptosis in cells. Moreover, melatonin markedly activated c-JUN N-terminal kinase (JNK) and p38 kinase, whereas extracellular signal-regulated kinase (ERK) was not responsive to melatonin. Treatment with MAPK inhibitors, PD98059 (ERK inhibitor), SP600125 (JNK inhibitor) and SB202190 (p38 inhibitor), confirmed that melatonin-induced apoptosis was JNK- and p38-dependent, but ERK-independent. In the presence of PD98059, caspase-3 activity increased, while levels of Bax/cytochrome c (Cyt c) and Bcl-2 decreased. These effects were opposite to those observed with SP600125 and SB202190 treatments. Together, these results strongly suggest that JNK and p38 activation directly participate in apoptosis induced by melatonin. Thus, melatonin may be of promise for anti-prostate cancer strategies. SN - 1600-079X UR - https://www.unboundmedicine.com/medline/citation/19522739/Melatonin_induces_apoptotic_death_in_LNCaP_cells_via_p38_and_JNK_pathways:_therapeutic_implications_for_prostate_cancer_ L2 - https://doi.org/10.1111/j.1600-079X.2009.00682.x DB - PRIME DP - Unbound Medicine ER -