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Inhibition of Myeloid Cell Leukemia 1 and Activation of Caspases Are Critically Involved in Gallotannin‐induced Apoptosis in Prostate Cancer Cells
Author(s) -
Park Eunkyung,
Kwon Hee Young,
Jung Ji Hoon,
Jung DeokBeom,
Jeong Arong,
Cheon Jinhong,
Kim Bonglee,
Kim SungHoon
Publication year - 2015
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5371
Subject(s) - du145 , cancer research , biology , prostate cancer , apoptosis , cell culture , microbiology and biotechnology , cancer , biochemistry , lncap , genetics
Although gallotannin contained in several medicinal plants was known to have multi‐biological activities, such as antioxidant, antiinflammatory, antimicrobial, immunomodulatory, and antitumor effects, the underlying apoptotic mechanism of gallotannin is not fully understood so far. Thus, in the present study, the apoptotic mechanism of gallotannin was elucidated in DU145, PC‐3, and M2182 prostate cancer cells in association with myeloid cell leukemia 1 (Mcl‐1) signaling. Gallotannin exerted dose‐dependent cytotoxicity in DU145, PC‐3, and M2182 prostate cancer cells. Also, gallotannin showed apoptotic morphological features and increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells and sub‐G1 accumulation in three prostate cancer cell lines. Consistently, gallotannin cleaved poly (ADP‐ribose) polymerase (PARP) and attenuated the expression of procaspases 9 and 3 in three prostate cancer cell lines. Furthermore, gallotannin attenuated the expression of survival genes such as Mcl‐1, B‐cell lymphoma 2, and B‐cell lymphoma 2 extra large in three prostate cancer cell lines. Interestingly, overexpression of Mcl‐1 reversed the ability of gallotannin to cleave PARP and increase sub‐G1 population in three prostate cancer cell lines. Conversely, silencing of Mcl‐1 enhanced apoptosis by gallotannin in three prostate cancer cell lines by FACSCalibur (Becton Dickinson, Franklin Lakes, NJ, USA). Taken together, our findings demonstrate that inhibition of Mcl‐1 and activation of caspases are critically involved in gallotannin‐induced apoptosis in prostate cancer cells. Copyright © 2015 John Wiley & Sons, Ltd.