Apoptotic and Autophagic Cell Death Effects of the Hexane Extract of Tropical Marine Algae Halymenia durvillei against Human Glioblastoma Cells: In vitro and in silico Studies
DOI:
https://doi.org/10.48048/tis.2024.7157Keywords:
Halymenia durvillei, Glioblastoma, Apoptosis, Autophagy, MacroalgaeAbstract
Glioblastoma (GBM) considered as aggressive brain cancer with high mortality rate in patients even after surgical resection. Resistant to chemotherapy is the major problem in GBM therapy. Discovery of novel bioactive compounds from algae is being investigated as alternative sources for potential treatment as well as prevention in glioblastoma. This study revealed the effects of marine red algae extract from hexane solvent fraction of Halymenia durvillei (HDHE) on proliferation and cell death in A172 human GBM cells. HDHE decreased proliferation and promoted cell cycle arrest at G2/M phase. HDHE induced apoptotic cell death in A172 cells through mitochondrial membrane dysfunction, the decrease of anti-apoptotic Bcl-2 protein expression, and activation of caspase 3/7. Moreover, HDHE increased intracellular reactive oxygen species (ROS) production and accumulation of LC3-II, an autophagic marker. The docked conformation of palmitic acid, a major component of HDHE, showed a high affinity binding to TP53 and Beclin-1 as cell death-related target molecules. This research conclusively demonstrated that HDHE might serve as a potent anticancer agent against glioblastoma by promoting apoptotic and autophagic cell death in A172 human GBM cells.
HIGHLIGHTS
- The palmitic acid-enriched extract of red alga Halymenia durvillei (HDHE) could inhibit proliferation of A172 human glioblastoma cells by arresting cell cycle at G2/M phase
- HDHE could induce both caspase-dependent apoptotic and autophagic death of A172 cells
- Palmitic acid, a major component of HDHE, showed a high affinity binding to TP53 and Beclin-1
- The extract could be beneficial to develop as chemopreventive agents or food supplements against glioblastoma
GRAPHICAL ABSTRACT
Downloads
Metrics
References
DN Louis, A Perry, G Reifenberger, AV Deimling, D Figarella-Branger, WK Cavenee, H Ohgaki, OD Wiestler, P Kleihues and DW Ellison. The 2016 world health organization classification of tumors of the central nervous system: A summary. Acta Neuropathol. 2016; 131, 803-20.
H Strobel, T Baisch, R Fitzel, K Schilberg, MD Siegelin, G Karpel-Massler, KM Debatin and MA Westhoff. Temozolomide and other alkylating agents in glioblastoma therapy. Biomedicines 2019; 7, 69.
AG Gutierrez-Rodriguez, C Juarez-Portilla, . Olivares-Banuelos and RC Zepeda. Anticancer activity of seaweeds. Drug Discov. Today 2018; 23, 434-47.
J Cotas, A Leandro, D Pacheco, AMM Goncalves and L Pereira. A comprehensive review of the nutraceutical and therapeutic applications of red seaweeds (Rhodophyta). Life 2020; 10, 19.
TA Fenoradosoa, C Laroche, C Delattre, V Dulong, DL Cerf, L Picton and P Michaud. Rheological behavior and non-enzymatic degradation of a sulfated galactan from Halymenia durvillei (Halymeniales, Rhodophyta). Appl. Biochem. Biotechnol. 2012; 167, 1303-13.
A Chaiwichien, T Samrit, S Osotprasit, P Kueakhai, P Sobhon, K Meemon, N Niamnont, P Manohong, K Pranweerapaiboon and M Tamtin. Evaluation of toxicity and anti-oxidation activity of the extracts from Halymenia durvillei. Trends Sci. 2022; 19, 3032.
K Sangpairoj, R Settacomkul, T Siangcham, K Meemon, N Niamnont, N Sornkaew, M Tamtin, P Sobhon and P Vivithanaporn. Hexadecanoic acid-enriched extract of Halymenia durvillei induces apoptotic and autophagic death of human triple-negative breast cancer cells by upregulating ER stress. Asian Pac. J. Trop. Biomed. 2022; 12, 132-40.
G Wolber, T Langer. LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. J. Chem. Inf. Model. 2005; 45, 160-9.
K Pranweerapaiboon, A Garon, T Seidel, S Janta, A Plubrukarn, K Chaithirayanon and T Langer. In vitro and in silico studies of holothurin A on androgen receptor in prostate cancer. J. Biomol. Struct. Dyn. 2022; 40, 12674-82.
S Sharifi, PG Mostafavi, R Tarasi, AM Moradi, MH Givianrad, MM Farimani, SN Ebrahimi, M Hamburger and H Niknejad. Purified compounds from marine organism sea pen induce apoptosis in human breast cancer cell MDA-MB-231 and cervical cancer cell Hela. Eur. J. Pharmacol. 2020; 877, 173075.
Y Yuan, N Shah, MI Almohaisin, S Saha and F Lu. Assessing fatty acid-induced lipotoxicity and its therapeutic potential in glioblastoma using stimulated Raman microscopy. Sci. Rep. 2021; 11, 7422.
S Jiapaer, T Furuta, Y Dong, T Kitabayashi, H Sabit, J Zhang, G Zhang, S Tanaka, M Kobayashi, A Hirao and M Nakada. Identification of 2-Fluoropalmitic acid as a potential therapeutic agent against glioblastoma. Curr. Pharm. Des. 2020; 26(36). 4675-84.
CM Pfeffer and ATK Singh. Apoptosis: A target for anticancer therapy. Int. J. Mol. Sci. 2018; 19, 448.
B Perillo, M Di Donato, A Pezone, ED Zazzo, P Giovannelli, G Galasso, G Castoria and A Migliaccio. ROS in cancer therapy: The bright side of the moon. Exp. Mol. Med. 2020; 52, 192-203.
A Escamilla-Ramírez, RA Castillo-Rodríguez, S Zavala-Vega, D Jimenez-Farfan, I Anaya-Rubio, E Briseño, G Palencia, P Guevara, A Cruz-Salgado, J Sotelo and C Trejo-Solís. Autophagy as a potential therapy for malignant glioma. Pharmaceuticals 2020; 13, 156.
J Wang and D Nie. Modulation of autophagy by free fatty acids. In: TM Ntuli (Ed.). Cell death-autophagy, apoptosis and necrosis. IntechOpen, London, 2015.
A Pal, P Verma, S Paul, I Majumder and R Kundu. Two species of Ulva inhibits the progression of cervical cancer cells SiHa by means of autophagic cell death induction. 3 Biotech 2021; 11, 52.
JC Sharpe, D Arnoult and RJ Youle. Control of mitochondrial permeability by Bcl-2 family members. Biochim. Biophys. Acta 2004; 1644, 107-13.
JA Hamilton and K Brunaldi. A Model for fatty acid transport into the brain. J. Mol. Neurosci. 2007; 33, 12-7.
RT Martuscello, V Vedam-Mai, DJ McCarthy, ME Schmoll, MA Jundi, CD Louviere, BG Griffith, CL Skinner, O Suslov, LP Deleyrolle and BA Reynolds. A supplemented high-fat low-carbohydrate diet for the treatment of glioblastoma. Clin. Cancer Res. 2016; 22, 2482-95.
EC Woolf and AC Scheck. The ketogenic diet for the treatment of malignant glioma. J. Lipid Res. 2015; 56, 5-10.
Y Zhang, C Dube, M Gibert Jr, N Cruickshanks, B Wang, M Coughlan, Y Yang, I Setiady, C Deveau, K Saoud, C Grello, M Oxford, F Yuan and R Abounader. The p53 pathway in glioblastoma. Cancers 2018; 10, 297.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Walailak University
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
