Mechanism of Pterostilbene-Induced Cell Death in HT-29 Colon Cancer Cells

Abstract

Pterostilbene is a dietary phytochemical that has been found to possess several biological activities, such as antioxidant and anti-inflammatory. Recent studies have shown that it exhibits the hallmark characteristics of an anticancer agent. The aim of the study was to investigate the anticancer activity of pterostilbene against HT-29 human colon cancer cells, focusing on its influence on cell growth, differentiation, and the ability of this stilbene to induce cell death. To clarify the mechanism of pterostilbene activity against colon cancer cells, changes in the expression of several genes and proteins that are directly related to cell proliferation, signal transduction pathways, apoptosis, and autophagy were also evaluated. Cell growth and proliferation of cells exposed to pterostilbene (5–100 µM) were determined by SRB and BRDU assays. Flow cytometric analyses were used for cell cycle progression. Further molecular investigations were performed using quantitative real-time RT-PCR. The expression of the signaling proteins studied was determined by the ELISA method. The results revealed that pterostilbene inhibited proliferation and induced the death of HT-29 colon cancer cells. Pterostilbene, depending on concentration, caused inhibition of proliferation, G1 cell arrest, and/or triggered apoptosis in HT-29 cells. These effects were mediated by the down-regulation of the STAT3 and AKT kinase pathways. It may be concluded that pterostilbene could be considered as a potential therapeutic option in the treatment of colon cancer in the future.

Synthesis, In Vitro, and In Vivo Investigations of Pterostilbene-Tethered Analogues as Anti-Breast Cancer Candidates

“…Coinciding with the previous literature [18][19][20][21][22], our tentative bioassay screening found that PTE possessed anti-proliferation properties against MDA-MB-231 (TNBC, IC50 = 63.59 μM) and MCF-7 (ER + BC, IC50 = 44.26 μM) cells. In this research, we aimed to obtain lead chemical entities with improved anti-BC activity through the structural optimization of PTE.…”

“…Similar to resveratrol, PTE exerts a broad spectrum of biological and pharmacological activities, including antioxidant, anti-inflammatory, anti-fungal, and anti-diabetic capacities [11,[15][16][17]. In addition, PTE has been recognized as a potential antitumor agent against multiple types of cancers, including prostate, liver, lung, gastric, and colon cancer [18][19][20][21][22]. Preliminary investigations of its mechanisms have found that the anticancer behavior of PTE is mainly ascribable to the induction of apoptosis, cell cycle arrest, autophagy, and DNA damage, thus, inhibiting the growth and proliferation of tumor cells [23][24][25][26].…”

Potential Chemopreventive Role of Pterostilbene in Its Modulation of the Apoptosis Pathway

“…Pterostilbene was also reported to induce apoptosis as it increased caspase-3 activity, DNA fragmentation, and the gene expression of BAX. At the higher dose, pterostilbene could regulate autophagy in HT-29 colon cancer cells as pterostilbene increased the gene expression of ULK1 that is responsible for initiating autophagy and increasing gene expression of AMBRA1 and LC3A which are encoded for proteins that are involved in autophagosome formation [124]. Pterostilbene also downregulates the protein expression of anti-apoptotic proteins of Bcl-2 and survivin [121].…”

3′‐Hydroxypterostilbene Potently Suppresses Tumor Growth via Inhibiting the Activation of the JAK2/STAT3 Pathway in Ovarian Clear Cell Carcinoma

“…[21] PSB has also been previously demonstrated to suppress cancer growth and induce cancer cell death via STAT3 pathway inhibition. [22,23] 3'-Hydroxypterostilbene (3HPSB) is an analog of pterostilbene hydroxylated at the 3' position of the B-ring of the stilbene backbone and is naturally found in the Chinese herb Sphaerophysa salsula. [24] 3HPSB has also been identified as a urinary metabolite of pterostilbene in a mouse model.…”