Betulinic Acid Modulates the Expression of HSPA and Activates Apoptosis in Two Cell Lines of Human Colorectal Cancer

Abstract

Betulinic acid (BA) is a pentacyclic triterpene usually isolated from botanical sources. Numerous studies have reported the inhibitory effect of BA against human colorectal cancer cells (CRC). However, its effect on the expression of the molecular chaperone HSPA is unclear. The aim of this research is to investigate the anti-cancer activities of BA purified from Piper retrofractum and study its effect on the expression of HSPA in colorectal cancer HCT116 and SW480 cells. The viability of both cancer cells was reduced after they were treated with an increasing dosage of BA. Flow cytometry assay revealed that levels of cell apoptosis significantly increased after incubation with BA in both cancer cells. Pro-apoptotic markers including Bax, cleaved-caspase-3 and cleaved-caspase-9 were increased while anti-apoptotic marker Bcl-2 was decreased after BA treatment. Western blot also showed that the expression of HSPA fluctuated upon BA treatment, whereby HSPA was increased at lower BA concentrations while at higher BA concentrations HSPA expression was decreased. Preliminary molecular docking assay showed that BA can bind to the nucleotide binding domain of the HSP70 at its ADP-bound state of the HSP70. Although further research is needed to comprehend the BA-HSPA interaction, our findings indicate that BA can be considered as potential candidate for the development of new treatment for colorectal cancer.

Histone Modification of Colorectal Cancer by Natural Products

“…Betulinic acid inhibits colon cancer cell growth and metastasis by regulating the TGF-β/Smad signaling pathway. It causes Smad protein receptor phosphorylation [ 109 ]. ANP32A is highly expressed in CRC tissues, correlating with their low differentiation, and is accompanied by the over-activation of AKT and reduced phosphorylation of p38.…”

Nutraceutical Role of Polyphenols and Triterpenes Present in the Extracts of Fruits and Leaves of Olea europaea as Antioxidants, Anti-Infectives and Anticancer Agents on Healthy Growth

“…A recent study showed that betulinic acid (BA) is capable of inhibiting cancer progression in two colorectal cancer lines, HCT116 and SW480, by interfering with the levels of pro-apoptotic markers, increasing the levels of cleaved Bax and caspase-3 and caspase-9, and decreasing those of the antiapoptotic Bcl2. At the same time, this triterpene was able to modify the levels of the HSPA chaperone according to the concentrations of BA used by being able to bind to the nucleotide-binding domain of HSP70 in its ADP-binding state, indicating its high anticancer capacity [ 121 ].…”