Resveratrol induces mitochondria-mediated, caspase-independent apoptosis in murine prostate cancer cells

Abstract

Found in the skins of red fruits, including grapes, resveratrol (RES) is a polyphenolic compound with cancer chemopreventive activity. Because of this activity, it has gained interest for scientific investigations. RES inhibits tumor growth and progression by targeting mitochondria-dependent or -independent pathways. However, further investigations are needed to explore the underlying mechanisms.The present study is focused on examining the role of RES-induced, mitochondria-mediated, caspase-independent apoptosis of prostate cancer cells, namely transgenic adenocarcinoma of mouse prostate (TRAMP) cells. These cells were exposed to RES for various times, and cell killing, cell morphology, mitochondrial membrane potential (Δψm), expression of Bax and Bcl2 proteins, the role of caspase-3, and DNA fragmentation were analyzed.TRAMP cells exposed to RES showed decreased cell viability, altered cell morphology, and disrupted Δψm, which led to aberrant expression of Bax and Bcl2 proteins. Furthermore, since the caspase-3 inhibitor, z-VAD-fmk (benzyloxycarbonyl-valine-alanine-aspartic acid-fluoromethyl ketone), had no appreciable impact on RES-induced cell killing, the killing was evidently caspase-independent. In addition, RES treatment of TRAMP-C1, TRAMP-C2, and TRAMP-C3 cells caused an appreciable breakage of genomic DNA into low-molecular-weight fragments.These findings show that, in inhibition of proliferation of TRAMP cells, RES induces mitochondria-mediated, caspase-independent apoptosis. Therefore, RES may be utilized as a therapeutic agent to control the proliferation and growth of cancer cells.

The Critical Role of PTEN/PI3K/AKT Signaling Pathway in Shikonin-Induced Apoptosis and Proliferation Inhibition of Chronic Myeloid Leukemia

“…Furthermore, the antitumor activities of shikonin are mediated through downregulation of anti-apoptotic proteins including Bcl-2 and Bcl-xL and induce caspase activation [26][27][28]. Bax migrates to the mitochondrial membrane and inhibits the action of Bcl-2, causing damage to the mitochondrial membrane that in turn releases cytochrome-c, which leads to apoptosis by the activation of caspase-3 and caspase-7 [29]. In our study, western blotting analysis indicated that shikonin treatment resulted in decreased expression of Bcl-2 and increased expression of Bax and cleaved caspase-3 in K562 cells.…”

Protective effects of resveratrol on osteoporosis via activation of the SIRT1‑NF‑κB signaling pathway in rats

“…Resveratrol regulates a series of signal transduction pathways, such as the SIRT1 and NF-κB signaling pathways (14). Resveratrol is also able to increase the quantity and function of mitochondria (15). Previous studies have demonstrated that various organs, such as the liver, brain, kidney and lung, in F2 hybrid mice appear to have oxidative DNA damage with aging (12,16,17).…”

Antitumour effects of selected plant polyphenols, gallic acid and ellagic acid, on sensitive and multidrug‐resistant leukaemia HL60 cells

“…The obtained results confirmed that both compounds triggered mostly the apoptotic death of sensitive leukaemic HL60 cells and their MDR (HL60/VINC and HL60/MX2) counterparts. Additionally, because there are some literature data reporting that certain bioactive plant compounds, including resveratrol, luteolin, anthocyanin, silymarin, and bioactive constituents of extracts obtained from Dillenia suffruticosa as well as from Pinus radiata , could induce nonclassical mechanisms of apoptotic cell death (Kapoor, ; Khorsandi, Saki, Bavarsad, & Mombeini, ; Kumar et al, ; Pozo‐Guisado et al, ; Reddivari, Vanamala, Chintharlapalli, Safe, & Miller, ; Tor et al, ; Venkatesan, Choi, Mun, & Kim, ); the effect of GA and EA on the activation of caspases involved in apoptosis was examined. The obtained results showed that EA used at IC 90 provoked a significant activation of caspase‐3 and caspase‐8 in all studied leukaemia cells indicating that this compound triggered caspase‐dependent apoptotic cell death.…”