3-Bromopyruvate potentiates TRAIL-induced apoptosis in human colon cancer cells through a reactive oxygen species- and caspase-dependent mitochondrial pathway

Abstract

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising anticancer cytokine with minimal toxicity towards normal cells. Nevertheless, most primary cancers are often intrinsically TRAIL-resistant or can acquire resistance after TRAIL therapy. This study aimed to investigate the inhibitory effect of co-treatment of 3-bromopyruvate (3-BP) as a potent anticancer agent with TRAIL on colon cancer cells (HT-29). The results of present study indicated that combined treatment with 3-BP and TRAIL inhibited the proliferation of HT-29 cells to a greater extent (88.4%) compared with 3-BP (54%) or TRAIL (11%) treatment alone. In contrast, the combination of 3-BP and TRAIL had no significant inhibitory effect on the proliferation of normal cells (HEK-293) (8.4%). At a cellular mechanistic level, the present study showed that 3-BP sensitized human colon cancer cells to TRAIL-induced apoptosis via reactive oxygen species generation, upregulation of Bax, downregulation of Bcl-2 and survivin, release of cytochrome c into the cytosol, and activation of caspase-3. In normal cells, 3-BP, TRAIL, or combination of both had no significant effect on the reactive oxygen species levels, release of cytochrome c, and caspase-3 activity. Therefore, the combination of 3-BP and TRAIL can be a promising therapeutic strategy for treatment of colon cancer.

Glycometabolic rearrangements--aerobic glycolysis in pancreatic cancer: causes, characteristics and clinical applications

“…2-Deoxy-D-glucose (2-DG) is an analog of glucose that has recently been used as an HK inhibitor because it can be phosphorylated by HKs but not catalyzed further [117]. Another small molecule, 3-bromopyruvate (3-BP), and the novel agent methyl jasmonate (MJ) can suppress glycolysis and cancer growth in cancer patients [118,119]. It was concluded that the lncRNA hox transcript antisense RNA (HOTAIR) is tightly linked with HK2 in PDAC patients.…”

Ginsenoside Rh2 inhibits HeLa cell energy metabolism and induces apoptosis by upregulating voltage‑dependent anion channel 1

“…4B and C ). Since caspase-9 is activated by Bcl-2 family proteins ( 36 ), it was investigated whether 20(S)-GRh2 affected the expression of Bcl-2 and Bax proteins. 45 µ M 20(S)-GRh2 induced Bax upregulation and Bcl-2 downregulation ( Fig.…”

The anticarcinogenic and anticancer effects of the dietary flavonoid, morin: Current status, challenges, and future perspectives

“…Nowadays, numerous studies have focused on the finding new anticancer agents with high efficacy and low toxicity (Pucci, Martinelli, & Ciofani, 2019). In this sense, flavonoids have attracted much attention owing to their potent antiproliferative effects with minimal toxicity against healthy tissues (Abbaszadeh, Ebrahimi, & Akhavan, 2014;Abbaszadeh, Valizadeh, et al, 2019). Therefore, flavonoids have the potential to be developed as promising chemopreventive and anticancer agents.…”

“…Studies have explored that one of the most significant drawbacks of flavonoids is their very low bioavailability that restricts their clinical use. The poor bioavailability of flavonoids is mainly attributed to their poor watersolubility (Abbaszadeh, Valizadeh, et al, 2019). Morin, as a dietary flavonoid with significant anticarcinogenic and anticancer effects, has been found to have a poor bioavailability, which is associated with its strategies have been employed to improve the oral bioavailability of morin (Choi et al, 2015;Ikeuchi-Takahashi et al, 2016;Zhang et al, 2011;.…”

“…The regulation of mitochondrial‐dependent apoptosis pathway is mediated by B‐cell lymphoma 2 (Bcl‐2) family members. The Bcl‐2 family consists of pro‐apoptotic proteins (e.g., Bax, Bad, Bak, Bik, and Bid) and anti‐apoptotic proteins (e.g., Bcl‐2, Bcl‐xL, BCL‐W, and MCL‐1) that control cell death by regulating the permeabilization of outer mitochondrial membrane (Abbaszadeh, Valizadeh, et al, 2019; Popgeorgiev, Jabbour, & Gillet, 2018). The pro‐apoptotic proteins facilitate the release of cytochrome c from mitochondria into cytosol to form the apoptosome complex in the cytosol together with apoptotic protein‐activating factor 1 (Apaf‐1) and procaspase‐9 (Gillies & Kuwana, 2014; Yadav et al, 2020).…”