Antidesma bunius aqueous crude extract promotes cell death via modulation of redox-sensitive and autophagy-associated genes in HCT 116 human-derived colorectal cancer cells

Authors

  • Sol Joaquin Benigno Chemistry Department, De La Salle University, 2401 Taft Avenue, Manila 0922
  • Glenn Oyong Center for Natural Sciences and Ecological Research (CENSER), De La Salle University, 2401 Taft Avenue, Manila 0922
  • Josafat John Licayan Chemistry Department, De La Salle University, 2401 Taft Avenue, Manila 0922
  • Rodolfo Sumayao Chemistry Department, De La Salle University, 2401 Taft Avenue, Manila 0922 http://orcid.org/0000-0001-6646-8931

Keywords:

Antidesma bunius, colorectal cancer, oxidative stress, antioxidants, autophagy, mitochondria

Abstract

Paper description:

  • Antidesma bunius fruit exhibits antioxidant properties. Its anticancer activities remain underexplored.
  • We investigated the effects of Antidesma bunius fruit aqueous extract (A. bunius ACE) on the redox status, mitochondrial integrity and expression of genes associated with oxidative stress (the state of redox imbalance), and autophagy (a cellular ‘housekeeping’ process) in the colorectal cancer cell line, HCT 116.
  • A. bunius ACE reduced the oxidative stress and enhanced mitochondrial integrity of HCT 116 cells, accompanied by upregulation of genes associated with oxidative stress and autophagy.
  • These changes point to a potential anti-cancer mechanism and underscore the therapeutic potential of A. bunius fruits.


Abstract: Antidesma bunius fruit was previously shown to exhibit antioxidant properties, but its anticancer activities remain underexplored. We hypothesized that the phytochemicals in this fruit can influence mitochondrial integrity and can modulate stress-responsive genes in cancer cells. The present study investigated the effects of A. bunius fruit aqueous crude extract (A. bunius ACE) on the viability, redox status, and mitochondrial transmembrane potential (MTP) using a colorectal cancer cell line, HCT 116. The expression of key genes associated with oxidative stress and autophagy was also determined. Treatment of cells with A. bunius ACE resulted in a ~27% reduction in viability, coupled with a marked decrease in oxidative stress index by ~59%. This was accompanied by the upregulation of NRF2 and NRF2-dependent genes. MTP increased ~3-fold in response to A. bunius ACE. The expression of BECLIN1, ATG5, and LC3 genes also increased. Our results indicate that the phytochemicals in A. bunius fruits enhance mitochondrial integrity and modulate the expression of stress-responsive genes, which may be responsible for the mitigation of oxidative stress in cancer cells. These alterations may be involved in the cascade of events leading to cancer cell death effected by A. bunius.

https://doi.org/10.2298/ABS200703037B

Received: July 3, 2020; Revised: August 24, 2020; Accepted: August 25, 2020; Published online: August 27, 2020

How to cite this article: Benigno SJ, Oyong G, Licayan JJ, Sumayao R Jr. Antidesma bunius aqueous crude extract promotes cell death via modulation of redox-sensitive and autophagy-associated genes in HCT 116 human-derived colorectal cancer cells. Arch Biol Sci. 2020;72(3):433-43.

Downloads

Download data is not yet available.

References

Islam S, Koly S. A review on phytochemical and pharmacological potentials of Antidesma bunius. J Anal Pharm Res. 2018;7:602-4.

Ibrahim TA, El Dib RA, Al-Youssef HM, Amina M. Chemical composition and antimicrobial and cytotoxic activities of Antidesm abunius L. Pak J Pharm Sci. 2019;32(1):153-63.

Jorjong S, Butkhup L, Samappito S. Phytochemicals and antioxidant capacities of Mao-Luang (Antidesma bunius L.) cultivars from Northeastern Thailand. Food Chem. 2015;181:248-55.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.

Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors. Prz Gastroenterol. 2019;14(2):89.

Sosa V, Moliné T, Somoza R, Paciucci R, Kondoh H, LLeonart ME. Oxidative stress and cancer: an overview. Ageing Res Rev. 2013;12(1):376-90.

Cadenas E. Mitochondrial free radical production and cell signaling. Mol Aspects Med. 2004;25(1-2):17-26.

Porporato PE, Filigheddu N, Bravo-San Pedro JM, Kroemer G, Galluzzi L. Mitochondrial metabolism and cancer. Cell Res. 2018;28(3):265-80.

Yun CW, Lee SH. The roles of autophagy in cancer. Int J Mol Sci. 2018;19(11):3466.

Vara-Perez M, Felipe-Abrio B, Agostinis P. Mitophagy in Cancer: A Tale of Adaptation. Cells. 2019;8(5):493.

Bakar A, Fadzelly M, Ismail NA, Isha A, Ling M, Lee A. Phytochemical composition and biological activities of selected wild berries (Rubus moluccanus L., R. fraxinifolius Poir., and R. alpestris Blume). Evid Based Complement Alternat Med. 2016;2016:2482930.

Ghasemzadeh A, Jaafar HZ, Rahmat A. Antioxidant activities, total phenolics and flavonoids content in two varieties of Malaysia young ginger (Zingiber officinale Roscoe). Molecules. 2010;15(6):4324-33.

Dróżdż P, Šėžienė V, Pyrzynska K. Phytochemical properties and antioxidant activities of extracts from wild blueberries and lingonberries. Plant Foods Hum Nutr. 2017;72(4):360-4.

Jakubowski W, Bartosz G. 2, 7-dichlorofluorescin oxidation and reactive oxygen species: what does it measure? Cell Biol Int. 2000;24(10):757-60.

Dhanani T, Shah S, Gajbhiye N, Kumar S. Effect of extraction methods on yield, phytochemical constituents and antioxidant activity of Withania somnifera. Arab J Chem. 2017;10:S1193-9.

Butkhup L, Samappito S. Changes in physico-chemical properties, polyphenol compounds and antiradical activity during development and ripening of maoluang (Antidesma bunius L. Spreng) fruits. J Fruit Ornam Plant Res. 2011;19(1):85-99.

Recuenco MC, Lacsamana MS, Hurtada WA, Sabularse VC. Total Phenolic and Total Flavonoid Contents of Selected Fruits in the Philippines. Philipp J Sci. 2016;145(3):275-81.

Panceri CP, Gomes TM, De Gois JS, Borges DL, Bordignon-Luiz MT. Effect of dehydration process on mineral content, phenolic compounds and antioxidant activity of Cabernet Sauvignon and Merlot grapes. Food Res Int. 2013;54(2):1343-50.

Middleton Jr E, Kandaswami C. Effects of flavonoids on immune and inflammatory cell functions. Biochem Pharmacol. 1992;43(6):1167-79.

Barcelo JM, Nullar ARM, Caranto JKP, Gatchallan AM, Aquino IJB. Antioxidant and antimutagenic activities of ripe Bignay (Antidesma bunius) crude fruit extract. Philipp J App Res Dev. 2016;6:32-43

Jeong S-M, Kim S-Y, Kim D-R, Jo S-C, Nam K, Ahn D, Lee S. Effect of heat treatment on the antioxidant activity of extracts from citrus peels. J Agric Food Chem. 2004;52(11):3389-93.

Shaimaa G, Mahmoud M, Mohamed M, Emam A. Effect of heat treatment on phenolic and flavonoid compounds and antioxidant activities of some Egyptian sweet and chilli pepper. Nat Prod Chem Res. 2016;4(3):1000218.

Shahidi F, Yeo J. Insoluble-bound phenolics in food. Molecules. 2016;21(9):1216.

Satti J. The emerging low-dose therapy for advanced cancers. Dose-Response. 2009; 24;7(3):208-20.

Gaya A, Akle CA, Mudan S, Grange J. The concept of hormesis in cancer therapy - Is less more? Cureus. 2015;7(4):1-14.

Xie X, Wu Y, Luo S, Yang H, Li L, Zhou S, Shen R, Lin H.. Efficacy and toxicity of low-dose versus conventional-dose chemotherapy for malignant tumors: a meta-analysis of 6 randomized controlled trials. Asian Pac J Cancer Prev. 2017;18(2):479.

Lee B, Moon KM, Kim CY. Tight junction in the intestinal epithelium: Its association with diseases and regulation by phytochemicals. J Immunol Res. 2018;2018.

Martin TA, Jiang WG. Loss of tight junction barrier function and its role in cancer metastasis. Biochim Biophys Acta. 2009;1788(4):872-91.

Liou G-Y, Storz P. Reactive oxygen species in cancer. Free Radic Res. 2010;44(5):479-96.

Sumayao R, McEvoy B, Newsholme P, McMorrow T. Lysosomal cystine accumulation promotes mitochondrial depolarization and induction of redox‐sensitive genes in human kidney proximal tubular cells. J Physiol. 2016;594(12):3353-70.

Cuadrado A, Rojo AI, Wells G, Hayes JD, Cousin SP, Rumsey WL, Attucks OC, Franklin S, Levonen A, Kensler TW, Dinkova-Kostova AT. Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nat Rev Drug Discov. 2019;18(4):295-317.

Zuo Q, Wu R, Xiao X, Yang C, Yang Y, Wang C, Lin L, Kong A. The dietary flavone luteolin epigenetically activates the Nrf2 pathway and blocks cell transformation in human colorectal cancer HCT116 cells. J Cell Biochem. 2018;119(11):9573-82.

Kang KA, Piao MJ, Hyun YJ, Zhen AX, Cho SJ, Ahn MJ, Yi JM, Hyun JW. Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells. Exp Mol Med. 2019;51(4):1-14.

Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35(4):495-516.

Downloads

Published

2020-10-19

How to Cite

1.
Benigno SJ, Oyong G, Licayan JJ, Sumayao R. Antidesma bunius aqueous crude extract promotes cell death via modulation of redox-sensitive and autophagy-associated genes in HCT 116 human-derived colorectal cancer cells. Arch Biol Sci [Internet]. 2020Oct.19 [cited 2024Apr.20];72(3):433-4. Available from: https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/5575

Issue

Section

Articles