Inhibition of Myeloid Cell Leukemia 1 and Activation of Caspases Are Critically Involved in Gallotannin‐induced Apoptosis in Prostate Cancer Cells

Abstract

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.

The Crosstalk between Prostate Cancer and Microbiota Inflammation: Nutraceutical Products Are Useful to Balance This Interplay?

“…In addition, GA reduces survival, proliferation, and invasion in PC3 cells [ 149 ]. Gallotannins, polymers formed by the esterification of GA, produce an apoptotic effect in DU145 and PC3 cell lines by decreasing the expression of different genes, such as Mcl-1, and inhibiting caspase activation [ 150 ]. Similarly, the ellagitannins of the pomegranate, named punicalagin (PN), have elicited the induction of apoptosis in PC-3 and LNCaP cells [ 151 ].…”

SIRT1 in the Development and Treatment of Hepatocellular Carcinoma

“…Gallotannin is a plant-derived compound with anticancer effects (125). Treating HCC cells with gallotannin in vitro resulted in reduced colony formation, amplified cytotoxicity, increased senescence, impaired autophagy, upregulated p21, and promoted cell death.…”

Scope of Hydrolysable Tannins as Possible Antimicrobial Agent

“…Terminalia chebula (Yoshida et al, 1980) Phyllanthusiins A Phyllanthus flexuosus (Yoshida et al, 1994) Euphorbins A-C 1989), antiinflammatory (Bharat Reddy et al, 2009;Reddy and Reddanna, 2009;Park et al, 2010;Shukla et al, 2008;Liu et al, 2015), anticancer (Miyamoto et al, 1993;Ito et al, 1999;Chrubasik-Hausmann et al, 2014;Gambari et al, 2014;Park et al, 2015), antibacterial (Taguri et al, 2004;Funatogawa et al, 2004;Parashar et al, 2009;Adesina et al, 2000;Akiyama et al, 2001;Miyasaki et al, 2013;Zhang et al, 2013;Fyhrquist et al, 2014), antiviral (Nonaka et al, 1990;Corthout et al, 1991;Kim et al, 2001;Cheng et al, 2002;Notka et al, 2003;Quideau et al, 2004;Lin et al, 2011;Lin et al, 2013;Abdel-Mageed and Bayoumi, 2014) and antifungal activities (Karunanayake et al, 2011;Glazer et al, 2012;Ascacio Valdés et al, 2013;Barros et al, 2013). This review addresses the antibacterial, antiviral and antifungal activities of HTs to identify them as possible antimicrobial agents in future.…”