Rutin and orlistat produce antitumor effects via antioxidant and apoptotic actions
- 73 Downloads
Cancer is a broad term used to describe a large number of diseases characterized by uncontrolled cell proliferation that leads to tumor production. Cancer is associated with mutations in genes controlling proliferation and apoptosis, oxidative stress, fatty acid synthase (FAS) expression, and other mechanisms. Currently, most antineoplastic drugs have severe adverse effects and new effective and safe drugs are needed. This study aims to investigate the possible anticancer activity of rutin and orlistat which are both safely used clinically in humans against two breast cancer models (in vivo EAC and in vitro MCF7) and the pancreatic cancer cell line (PANC-1). Our results have shown that both rutin and orlistat exerted an in vivo anticancer activity as evidenced by the decrease in tumor volume, CEA level, cholesterol content, FAS, and the exerted antioxidant action (reduced MDA level and increased GSH content) and through histopathological examination. In addition, both were cytotoxic to MCF-7 and Panc-1 cell lines by promoting apoptosis. In conclusion, the anticancer activity of rutin and orlistat makes them promising candidates for cancer treatment alone or in combination with other anticancer drugs specially that they are used clinically with an acceptable safety profile.
KeywordsRutin Orlistat Ehrlich ascites carcinoma Mice MCF-7 PANC-1
AS performed the in vivo study and analyzed data. HE designed the study and revised the manuscript. MY performed the in vitro study. WB designed the study, analyzed data, and revised the manuscript. All authors read and approved the manuscript.
Compliance with ethical standards
All experimental procedures were approved by the Ethical Committee for Animal Handling at Zagazig University (ECAHZU).
Conflict of interest
The authors declare that they have no conflict of interests.
- Auersperg M, PogaÄ nik A, Kloboves-Prevodnik V, Serša G, Čemažar M (2006) Schedule-dependency of doxorubicin and vinblastine in EAT tumours in mice. Radiol Oncol 40(4)Google Scholar
- Chen H, Miao Q, Geng M, Liu J, Hu Y, Tian L, Pan J, Yang Y (2013) Anti-tumor effect of rutin on human neuroblastoma cell lines through inducing G2/M cell cycle arrest and promoting apoptosis. Sci World J 2013:1–8Google Scholar
- da Mota MF, de Carvalho FS, de Avila RI, de Avila PHM, Cortez AP, Menegatti R et al (2018) LQFM030 reduced Ehrlich ascites tumor cell proliferation and VEGF levels. Life Sci 201(1–8)Google Scholar
- El-Ashmawy NE, Khedr NF, El-Bahrawy HA, Mansour HEA (2017) Ginger extract adjuvant to doxorubicin in mammary carcinoma: study of some molecular mechanisms. Eur J Nutr:1–9Google Scholar
- Gumulec J, Fojtu M, Raudenska M, Sztalmachova M, Skotakova A, Vlachova J, Skalickova S, Nejdl L, Kopel P, Knopfova L, Adam V, Kizek R, Stiborova M, Babula P, Masarik M (2014) Modulation of induced cytotoxicity of doxorubicin by using apoferritin and liposomal cages. Int J Mol Sci 15(12):22960–22977PubMedPubMedCentralCrossRefGoogle Scholar
- Hasanpourghadi M, Abdul Majid N, Rais Mustafa M (2018) The role of miRNAs 34a, 146a, 320a and 542 in the synergistic anticancer effects of methyl 2-(5-fluoro-2-hydroxyphenyl)-1H- benzo[d]imidazole-5-carboxylate (MBIC) with doxorubicin in breast cancer cells. PeerJ 6:e5577PubMedPubMedCentralCrossRefGoogle Scholar
- Jelinek D, Castillo JJ, Richardson LM, Luo L, Heidenreich RA, Garver WS (2012) The Niemann-Pick C1 gene is downregulated in livers of C57BL/6J mice by dietary fatty acids, but not dietary cholesterol, through feedback inhibition of the SREBP pathway. J Nutr 142(11):1935–1942PubMedPubMedCentralCrossRefGoogle Scholar
- Migita T, Ruiz S, Fornari A, Fiorentino M, Priolo C, Zadra G, Inazuka F, Grisanzio C, Palescandolo E, Shin E, Fiore C, Xie W, Kung AL, Febbo PG, Subramanian A, Mucci L, Ma J, Signoretti S, Stampfer M, Hahn WC, Finn S, Loda M (2009) Fatty acid synthase: a metabolic enzyme and candidate oncogene in prostate cancer. J Natl Cancer Inst 101(7):519–532PubMedPubMedCentralCrossRefGoogle Scholar
- Oak C, Khalifa AO, Isali I, Bhaskaran N, Walker E, Shukla S (2018) Diosmetin suppresses human prostate cancer cell proliferation through the induction of apoptosis and cell cycle arrest. Int J OncolGoogle Scholar
- Posey LM (2005) Cancer treatment and chemotherapy, Pharmacotherapy: a pathophysiologic approach. McGraw-Hill, New YorkGoogle Scholar
- Rossi S, Graner E, Febbo P, Weinstein L, Bhattacharya N, Onody T et al (2003) Fatty acid synthase expression defines distinct molecular signatures in prostate cancer1 1 NCI (Director’s Challenge CA84995-04, SPORE in Prostate Cancer CA90381-01A1, and PO1 CA89021-02), Novartis Investigator, and CaPCURE awards. Mol Cancer Res 1(10):707–715PubMedGoogle Scholar
- Rouibah H, Kebsa W, Lahouel M, Zihlif M, Ahram M, Aburmeleih B, Mustafa E, el-Amir H (2018) Algerian propolis potentiates doxorubicin mediated anticancer effect against human pancreatic PANC-1 Cancer cell line through cell cycle arrest, apoptosis induction and P-glycoprotein inhibition. Anti Cancer Agents Med Chem 18(3):375–387CrossRefGoogle Scholar
- Roy A, Sarker S, Upadhyay P, Pal A, Adhikary A, Jana K, Ray M (2018) Methylglyoxal at metronomic doses sensitizes breast cancer cells to doxorubicin and cisplatin causing synergistic induction of programmed cell death and inhibition of stemness. Biochem Pharmacol 156:322–339PubMedCrossRefGoogle Scholar
- Salazar AT, Hoheisel J, Youns M, Wink M (2011) Anti-inflammatory and anti-cancer activities of essential oils and their biological constituents. Int J Clin Pharmacol Ther 49(1):93–95Google Scholar
- Tomankova K, Polakova K, Pizova K, Binder S, Havrdova M, Kolarova M, Kriegova E, Zapletalova J, Malina L, Horakova J, Malohlava J, Kolokithas-Ntoukas A, Bakandritsos A, Kolarova H, Zboril R (2015) In vitro cytotoxicity analysis of doxorubicin-loaded/superparamagnetic iron oxide colloidal nanoassemblies on MCF7 and NIH3T3 cell lines. Int J Nanomedicine 10:949–961PubMedPubMedCentralCrossRefGoogle Scholar
- Wysham WZ, Roque DR, Han J, Zhang L, Guo H, Gehrig PA et al (2016) Effects of fatty acid synthase inhibition by orlistat on proliferation of endometrial cancer cell lines. Target Oncol:1–7Google Scholar
- Zheng S, Wang X, Weng YH, Jin X, Ji JL, Guo L, Hu B, Liu N, Cheng Q, Zhang J, Bai H, Yang T, Xia XH, Zhang HY, Gao S, Huang Y (2018) siRNA knockdown of RRM2 effectively suppressed pancreatic tumor growth alone or synergistically with doxorubicin. Mol Ther Nucleic Acids 12:805–816PubMedPubMedCentralCrossRefGoogle Scholar