Proteomic Analysis on Anti-Proliferative and Apoptosis Effects of Curcumin Analog, 1,5-bis(4-Hydroxy-3-Methyoxyphenyl)-1,4-Pentadiene-3-One-Treated Human Glioblastoma and Neuroblastoma Cells

Abstract

Curcumin analogs with excellent biological properties have been synthesized to address and overcome the poor pharmacokinetic profiles of curcumin. This study aims to investigate the cytotoxicity, anti-proliferative, and apoptosis-inducing ability of curcumin analog, MS13 on human glioblastoma U-87 MG, and neuroblastoma SH-SY5Y cells, and to examine the global proteome changes in these cells following treatment. Our current findings showed that MS13 induced potent cytotoxicity and anti-proliferative effects on both cells. Increased caspase-3 activity and decreased bcl-2 concentration upon treatment indicate that MS13 induces apoptosis in these cells in a dose- and time-dependent manner. The label-free shotgun proteomic analysis has defined the protein profiles in both glioblastoma and neuroblastoma cells, whereby a total of nine common DEPs, inclusive of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), alpha-enolase (ENO1), heat shock protein HSP 90-alpha (HSP90AA1), Heat shock protein HSP 90-beta (HSP90AB1), Eukaryotic translation initiation factor 5A-1 (EFI5A), heterogenous nuclear ribonucleoprotein K (HNRNPK), tubulin beta chain (TUBB), histone H2AX (H2AFX), and Protein SET were identified. Pathway analysis further elucidated that MS13 may induce its anti-tumor effects in both cells via the common enriched pathways, “Glycolysis” and “Post-translational protein modification.” Conclusively, MS13 demonstrates an anti-cancer effect that may indicate its potential use in the management of brain malignancies.

Diarylpentanoid (1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one) (MS13) Exhibits Anti-proliferative, Apoptosis Induction and Anti-migration Properties on Androgen-independent Human Prostate Cancer by Targeting Cell Cycle–Apoptosis and PI3K Signalling Pathways

“…Besides, MS13 exhibits lower toxicity and highly selective towards PCa cells than normal cells, as indicated by SX values. MS13 showed better cytotoxic activity compared to the parent compound, curcumin against human normal cells, which was consistent with the data described previously (Citalingam et al, 2015;Paulraj et al, 2015;Ismail et al, 2020;Lee et al, 2021). An earlier study reported that FLLL11, which has an identical chemical structure as MS13 was less cytotoxic as curcumin towards human normal cell lines of lung fibroblast (WI-38), bladder smooth muscle and mammary epithelial (non-malignant MCF-10A) (Cen et al, 2009).…”

“…Previously, our group has reported that MS13 (1,5-Bis (4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one), a DAP, (Figure 1B demonstrated growth inhibitory effects in time-and dosedependent manner in prostate (Citalingam et al, 2015), cervical (Paulraj et al, 2015), glioblastoma, neuroblastoma (Lee et al, 2021), and colorectal (Ismail et al, 2020) cancer cell lines. Furthermore, MS13 has also shown to be effective than curcumin in inducing apoptosis by modulating apoptosis pathways in gastric (Yoshida et al, 2018), colorectal (Cen et al, 2009) and pancreatic (Friedman et al, 2009) cancer cells.…”

Mycoplasma suis Alpha-Enolase Subunit Vaccine Induces an Immune Response in Experimental Animals

“…Notably, those findings are consistent with our findings for the interaction network (Figure 10). Alpha-enolase is not only an adhesive protein, but is also likely involved in other roles concerning glycolysis [6,36]. The results of the protein interaction network are worthy of further study.…”

In Vitro and In Silico Study on the Impact of Chlorogenic Acid in Colorectal Cancer Cells: Proliferation, Apoptosis, and Interaction with β-Catenin and LRP6

“…Strategies to improve its pharmacokinetic profile could be a perspective of this work. For instance, some studies have shown that structural modifications of polyphenols, such as resveratrol and curcumin, increased their cytotoxic, antiproliferative, and proapoptotic effect [ 47 , 48 ]. Particularly, we have initiated a new project where we synthesize derivatives of CGA that showed a lower IC50 than CGA.…”