Bergamot natural products eradicate cancer stem cells (CSCs) by targeting mevalonate, Rho-GDI-signalling and mitochondrial metabolism

Biochimica et Biophysica Acta - Bioenergetics

Volumn 1859, Issue 9, 2018, Pages 984-996

  Fiorillo, Marco ^a,b,c   Peiris Pagès, Maria ^a   Sanchez Alvarez, Rosa ^a   Bartella, Lucia ^c   Di Donna, Leonardo ^c   Dolce, Vincenza ^c   Sindona, Giovanni ^c   Sotgia, Federica ^a,b   Cappello, Anna Rita ^c   Lisanti, Michael P ^a,b  

^a UNIVERSITY OF MANCHESTER   (United Kingdom)

^b UNIVERSITY OF SALFORD   (United Kingdom)

^c UNIVERSITY OF CALABRIA   (Italy)

Author keywords

Bergamot; Breast cancer; CSCs signalling; HMGR; Mevalonate pathway inhibitor; Rho GDI signalling

Indexed keywords

ANTINEOPLASTIC AGENT; BETA CATENIN; BMF; CHOLESTEROL; CYCLIN D; CYCLIN E; FLAVONOID; HYDROXYMETHYLGLUTARYL COENZYME A SYNTHASE; MEVALONIC ACID; MITOCHONDRIAL PROTEIN; NATURAL PRODUCT; OXYGEN; PRAVASTATIN; RHO GUANINE NUCLEOTIDE DISSOCIATION INHIBITOR; SIMVASTATIN; UNCLASSIFIED DRUG; BERGAMOT OIL; BIOLOGICAL PRODUCT; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; TUMOR MARKER; VEGETABLE OIL;

ARTICLE; BREAST CANCER; CANCER CONTROL; CANCER STEM CELL; CANCER SURVIVAL; CELL PROLIFERATION; CELL VIABILITY; CELLS; CONTROLLED STUDY; DISEASE ERADICATION; DRUG TARGETING; ENZYME ACTIVITY; FATTY ACID OXIDATION; G1 PHASE CELL CYCLE CHECKPOINT; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; IC50; LIQUID CHROMATOGRAPHY; MITOCHONDRIAL RESPIRATION; OVERALL SURVIVAL; OXYGEN CONSUMPTION; PRIORITY JOURNAL; RECURRENCE FREE SURVIVAL; SIGNAL TRANSDUCTION; UPREGULATION; WESTERN BLOTTING; APOPTOSIS; BREAST TUMOR; CELL CULTURE; CHEMISTRY; CYTOLOGY; DRUG EFFECT; FEMALE; FIBROBLAST; GENE EXPRESSION REGULATION; METABOLISM; METASTASIS; MITOCHONDRION; PATHOLOGY; PROGNOSIS; SURVIVAL RATE;

APOPTOSIS; BIOLOGICAL PRODUCTS; BIOMARKERS, TUMOR; BREAST NEOPLASMS; CELL PROLIFERATION; CELLS, CULTURED; FEMALE; FIBROBLASTS; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; HYDROXYMETHYLGLUTARYL COA REDUCTASES; MEVALONIC ACID; MITOCHONDRIA; NEOPLASM METASTASIS; NEOPLASTIC STEM CELLS; PLANT OILS; PROGNOSIS; RHO-SPECIFIC GUANINE NUCLEOTIDE DISSOCIATION INHIBITORS; SIGNAL TRANSDUCTION; SURVIVAL RATE;

EID: 85045106541     PISSN: 00052728     EISSN: 18792650     Source Type: Journal    
DOI: 10.1016/j.bbabio.2018.03.018     Document Type: Article

References (59)

1. Berry, D.A., Cronin, K.A., Plevritis, S.K., Fryback, D.G., Clarke, L., Zelen, M., Mandelblatt, J.S., Yakovlev, A.Y., Habbema, J.D., Feuer, E.J., Cancer, I., C. Surveillance Modeling Network, Effect of screening and adjuvant therapy on mortality from breast cancer. N. Engl. J. Med. 353 (2005), 1784–1792.
2. Mei, Z., Liang, M., Li, L., Zhang, Y., Wang, Q., Yang, W., Effects of statins on cancer mortality and progression: a systematic review and meta-analysis of 95 cohorts including 1,111,407 individuals. Int. J. Cancer 140 (2017), 1068–1081.
3. Ahern, T.P., Lash, T.L., Damkier, P., Christiansen, P.M., Cronin-Fenton, D.P., Statins and breast cancer prognosis: evidence and opportunities. Lancet Oncol. 15 (2014), e461–468.
4. Pisanti, S., Picardi, P., Ciaglia, E., D'Alessandro, A., Bifulco, M., Novel prospects of statins as therapeutic agents in cancer. Pharmacol. Res. 88 (2014), 84–98.
5. Yeganeh, B., Wiechec, E., Ande, S.R., Sharma, P., Moghadam, A.R., Post, M., Freed, D.H., Hashemi, M., Shojaei, S., Zeki, A.A., Ghavami, S., Targeting the mevalonate cascade as a new therapeutic approach in heart disease, cancer and pulmonary disease. Pharmacol. Ther. 143 (2014), 87–110.
6. Tanaka, K., Osada, H., Murakami-Tonami, Y., Horio, Y., Hida, T., Sekido, Y., Statin suppresses Hippo pathway-inactivated malignant mesothelioma cells and blocks the YAP/CD44 growth stimulatory axis. Cancer Lett. 385 (2017), 215–224.
7. Ginestier, C., Monville, F., Wicinski, J., Cabaud, O., Cervera, N., Josselin, E., Finetti, P., Guille, A., Larderet, G., Viens, P., Sebti, S., Bertucci, F., Birnbaum, D., Charafe-Jauffret, E., Mevalonate metabolism regulates Basal breast cancer stem cells and is a potential therapeutic target. Stem Cells 30 (2012), 1327–1337.
8. Jordan, C.T., Guzman, M.L., Noble, M., Cancer stem cells - reply. N. Engl. J. Med., 355, 2006, 2703.
9. Reya, T., Morrison, S.J., Clarke, M.F., Weissman, I.L., Stem cells, cancer, and cancer stem cells. Nature 414 (2001), 105–111.
10. Magee, J.A., Piskounova, E., Morrison, S.J., Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 21 (2012), 283–296.
11. Jordan, C.T., Guzman, M.L., Noble, M., Mechanisms of disease - cancer stem cells. N. Engl. J. Med. 355 (2006), 1253–1261.
12. Dontu, G., Al-Hajj, M., Abdallah, W.M., Clarke, M.F., Wicha, M.S., Stem cells in normal breast development and breast cancer. Cell Prolif. 36:Suppl. 1 (2003), 59–72.
13. Brooks, M.D., Burness, M.L., Wicha, M.S., Therapeutic implications of cellular heterogeneity and plasticity in breast cancer. Cell Stem Cell 17 (2015), 260–271.
14. Ginestier, C., Charafe-Jauffret, E., Birnbaum, D., Targeting breast cancer stem cells: fishing season open. Breast Cancer Res., 12, 2010, 312.
15. Peiris-Pages, M., Martinez-Outschoorn, U.E., Pestell, R.G., Sotgia, F., Lisanti, M.P., Cancer stem cell metabolism. Breast Cancer Res., 18, 2016, 55.
16. Gauthaman, K., Fong, C.Y., Bongso, A., Statins, stem cells, and cancer. J. Cell. Biochem. 106 (2009), 975–983.
17. Jiang, P., Mukthavaram, R., Chao, Y., Nomura, N., Bharati, I.S., Fogal, V., Pastorino, S., Teng, D., Cong, X., Pingle, S.C., Kapoor, S., Shetty, K., Aggrawal, A., Vali, S., Abbasi, T., Chien, S., Kesari, S., In vitro and in vivo anticancer effects of mevalonate pathway modulation on human cancer cells. Br. J. Cancer 111 (2014), 1562–1571.
18. Thurnher, M., Gruenbacher, G., Nussbaumer, O., Regulation of mevalonate metabolism in cancer and immune cells. Biochim. Biophys. Acta 1831 (2013), 1009–1015.
19. Greenwood, J., Steinman, L., Zamvil, S.S., Statin therapy and autoimmune disease: from protein prenylation to immunomodulation. Nat. Rev. Immunol. 6 (2006), 358–370.
20. Malachowski, S.J., Quattlebaum, A.M., Miladinovic, B., Adverse effects of statins. JAMA 317 (2017), 1079–1080.
21. du Souich, P., Roederer, G., Dufour, R., Myotoxicity of Statins: Mechanism of action. Pharmacol. Ther. 175 (2017), 1–16.
22. Lin, S.H., Huang, K.J., Weng, C.F., Shiuan, D., Exploration of natural product ingredients as inhibitors of human HMG-CoA reductase through structure-based virtual screening. Drug Des. Devel. Ther. 9 (2015), 3313–3324.
23. Harborne, J.B., Williams, C.A., Advances in flavonoid research since 1992. Phytochemistry 55 (2000), 481–504.
24. Patti, A.M., Toth, P.P., Giglio, R.V., Banach, M., Noto, M., Nikolic, D., Montalto, G., Rizzo, M., Nutraceuticals as an important part of combination therapy in dyslipidaemia. Curr. Pharm. Des. 23:17 (2017), 2496–2503.
25. Benavente-Garcia, O., Castillo, J., Alcaraz, M., Vicente, V., Del Rio, J.A., Ortuno, A., Beneficial action of Citrus flavonoids on multiple cancer-related biological pathways. Curr. Cancer Drug Targets 7 (2007), 795–809.
26. Yin, D., Li, J., Lei, X., Liu, Y., Yang, Z., Chen, K., Antiviral activity of total flavonoid extracts from selaginella moellendorffii Hieron against coxsackie virus B3 in vitro and in vivo. Evid. Based Complement. Alternat. Med., 2014, 2014, 950817.
27. Mandalari, G., Bennett, R.N., Bisignano, G., Trombetta, D., Saija, A., Faulds, C.B., Gasson, M.J., Narbad, A., Antimicrobial activity of flavonoids extracted from bergamot (Citrus bergamia Risso) peel, a byproduct of the essential oil industry. J. Appl. Microbiol. 103 (2007), 2056–2064.
28. Kim, H.P., Son, K.H., Chang, H.W., Kang, S.S., Anti-inflammatory plant flavonoids and cellular action mechanisms. J. Pharmacol. Sci. 96 (2004), 229–245.
29. Peluso, I., Miglio, C., Morabito, G., Ioannone, F., Serafini, M., Flavonoids and immune function in human: a systematic review. Crit. Rev. Food Sci. Nutr. 55 (2015), 383–395.
30. Gattuso, G., Barreca, D., Gargiulli, C., Leuzzi, U., Caristi, C., Flavonoid composition of Citrus juices. Molecules 12 (2007), 1641–1673.
31. Nogata, Y., Sakamoto, K., Shiratsuchi, H., Ishii, T., Yano, M., Ohta, H., Flavonoid composition of fruit tissues of citrus species. Biosci. Biotechnol. Biochem. 70 (2006), 178–192.
32. Cappello, A.R., Dolce, V., Iacopetta, D., Martello, M., Fiorillo, M., Curcio, R., Muto, L., Dhanyalayam, D., Bergamot (Citrus bergamia Risso) flavonoids and their potential benefits in human hyperlipidemia and atherosclerosis: an overview. Mini-Rev. Med. Chem. 16 (2016), 619–629.
33. Di Donna, L., De Luca, G., Mazzotti, F., Napoli, A., Salerno, R., Taverna, D., Sindona, G., Statin-like principles of bergamot fruit (Citrus bergamia): isolation of 3-hydroxymethylglutaryl flavonoid glycosides. J. Nat. Prod. 72 (2009), 1352–1354.
34. Di Donna, L., Iacopetta, D., Cappello, A.R., Gallucci, G., Martello, E., Fiorillo, M., Dolce, V., Sindona, G., Hypocholesterolaemic activity of 3-hydroxy-3-methyl-glutaryl flavanones enriched fraction from bergamot fruit (Citrus bergamia): “in vivo” studies. J. Funct. Foods 7 (2014), 558–568.
35. Ginestier, C., Wicha, M.S., Mammary stem cell number as a determinate of breast cancer risk. Breast Cancer Res., 9, 2007, 109.
36. Ginestier, C., Hur, M.H., Charafe-Jauffret, E., Monville, F., Dutcher, J., Brown, M., Jacquemier, J., Viens, P., Kleer, C.G., Liu, S., Schott, A., Hayes, D., Birnbaum, D., Wicha, M.S., Dontu, G., ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1 (2007), 555–567.
37. Carnero, A., Garcia-Mayea, Y., Mir, C., Lorente, J., Rubio, I.T., ME, L.L., The cancer stem-cell signaling network and resistance to therapy. Cancer Treat. Rev. 49 (2016), 25–36.
38. Liu, S., Dontu, G., Wicha, M.S., Mammary stem cells, self-renewal pathways, and carcinogenesis. Breast Cancer Res. 7 (2005), 86–95.
39. Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J.T., Bokesch, H., Kenney, S., Boyd, M.R., New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst. 82 (1990), 1107–1112.
40. Balachandran, R., ter Haar, E., Yalowich, J.C., Welsh, M.J., Grant, S.G., Day, B.W., Induction of human breast cancer cell apoptosis from G2/M preceded by stimulation into the cell cycle by Z-1,1-dichloro-2,3-diphenylcyclopropane. Biochem. Pharmacol. 57 (1999), 97–110.
41. Fiorillo, M., Lamb, R., Tanowitz, H.B., Cappello, A.R., Martinez-Outschoorn, U.E., Sotgia, F., Lisanti, M.P., Bedaquiline, an FDA-approved antibiotic, inhibits mitochondrial function and potently blocks the proliferative expansion of stem-like cancer cells (CSCs). Aging (Albany NY) 8 (2016), 1593–1607.
42. Fiorillo, M., Lamb, R., Tanowitz, H.B., Mutti, L., Krstic-Demonacos, M., Cappello, A.R., Martinez-Outschoorn, U.E., Sotgia, F., Lisanti, M.P., Repurposing atovaquone: targeting mitochondrial complex III and OXPHOS to eradicate cancer stem cells. Oncotarget 7 (2016), 34084–34099.
43. Johnson, S.M., Dempsey, C., Chadwick, A., Harrison, S., Liu, J., Di, Y., McGinn, O.J., Fiorillo, M., Sotgia, F., Lisanti, M.P., Parihar, M., Krishnan, S., Saha, V., Metabolic reprogramming of bone marrow stromal cells by leukemic extracellular vesicles in acute lymphoblastic leukemia. Blood 128 (2016), 453–456.
44. Peiris-Pages, M., Sotgia, F., Lisanti, M.P., Chemotherapy induces the cancer-associated fibroblast phenotype, activating paracrine Hedgehog-GLI signalling in breast cancer cells. Oncotarget 6 (2015), 10728–10745.
45. Shaw, F.L., Harrison, H., Spence, K., Ablett, M.P., Simoes, B.M., Farnie, G., Clarke, R.B., A detailed mammosphere assay protocol for the quantification of breast stem cell activity. J. Mammary Gland Biol. Neoplasia 17 (2012), 111–117.
46. Peiris-Pages, M., Smith, D.L., Gyorffy, B., Sotgia, F., Lisanti, M.P., Proteomic identification of prognostic tumour biomarkers, using chemotherapy-induced cancer-associated fibroblasts. Aging (Albany NY) 7 (2015), 816–838.
47. Waugh, D.J., Wilson, C., The interleukin-8 pathway in cancer. Clin. Cancer Res. 14 (2008), 6735–6741.
48. Van Overmeire, E., Stijlemans, B., Heymann, F., Keirsse, J., Morias, Y., Elkrim, Y., Brys, L., Abels, C., Lahmar, Q., Ergen, C., Vereecke, L., Tacke, F., De Baetselier, P., Van Ginderachter, J.A., Laoui, D., M-CSF and GM-CSF receptor signaling differentially regulate monocyte maturation and macrophage polarization in the tumor microenvironment. Cancer Res. 76 (2016), 35–42.
49. Shao, N., Lu, Z., Zhang, Y., Wang, M., Li, W., Hu, Z., Wang, S., Lin, Y., Interleukin-8 upregulates integrin beta3 expression and promotes estrogen receptor-negative breast cancer cell invasion by activating the PI3K/Akt/NF-kappaB pathway. Cancer Lett. 364 (2015), 165–172.
50. Waghray, M., Yalamanchili, M., Dziubinski, M., Zeinali, M., Erkkinen, M., Yang, H., Schradle, K.A., Urs, S., Pasca Di Magliano, M., Welling, T.H., Palmbos, P.L., Abel, E.V., Sahai, V., Nagrath, S., Wang, L., Simeone, D.M., GM-CSF mediates mesenchymal-epithelial cross-talk in pancreatic cancer. Cancer Discov. 6 (2016), 886–899.
51. Kazi, A., Carie, A., Blaskovich, M.A., Bucher, C., Thai, V., Moulder, S., Peng, H., Carrico, D., Pusateri, E., Pledger, W.J., Berndt, N., Hamilton, A., Sebti, S.M., Blockade of protein geranylgeranylation inhibits Cdk2-dependent p27Kip1 phosphorylation on Thr187 and accumulates p27Kip1 in the nucleus: implications for breast cancer therapy. Mol. Cell. Biol. 29 (2009), 2254–2263.
52. Besson, A., Hwang, H.C., Cicero, S., Donovan, S.L., Gurian-West, M., Johnson, D., Clurman, B.E., Dyer, M.A., Roberts, J.M., Discovery of an oncogenic activity in p27Kip1 that causes stem cell expansion and a multiple tumor phenotype. Genes Dev. 21 (2007), 1731–1746.
53. Liu, S., Wicha, M.S., Targeting breast cancer stem cells. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 28 (2010), 4006–4012.
54. Gauthaman, K., Manasi, N., Bongso, A., Statins inhibit the growth of variant human embryonic stem cells and cancer cells in vitro but not normal human embryonic stem cells. Br. J. Pharmacol. 157 (2009), 962–973.
55. Sorscher, S., Clinical confirmation of an anti-metastasis effect from statins. Int. J. Biochem. Cell Biol., 57, 2014, 207.
56. Stine, J.E., Guo, H., Sheng, X., Han, X., Schointuch, M.N., Gilliam, T.P., Gehrig, P.A., Zhou, C., Bae-Jump, V.L., The HMG-CoA reductase inhibitor, simvastatin, exhibits anti-metastatic and anti-tumorigenic effects in ovarian cancer. Oncotarget 7:1 (2016), 946–960.
57. Ginestier, C., Liu, S., Diebel, M.E., Korkaya, H., Luo, M., Brown, M., Wicinski, J., Cabaud, O., Charafe-Jauffret, E., Birnbaum, D., Guan, J.L., Dontu, G., Wicha, M.S., CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J. Clin. Invest. 120 (2010), 485–497.
58. Kakarala, M., Brenner, D.E., Korkaya, H., Cheng, C., Tazi, K., Ginestier, C., Liu, S., Dontu, G., Wicha, M.S., Targeting breast stem cells with the cancer preventive compounds curcumin and piperine. Breast Cancer Res. Treat. 122 (2010), 777–785.
59. Chung, S.S., Vadgama, J.V., Curcumin and epigallocatechin gallate inhibit the cancer stem cell phenotype via down-regulation of STAT3-NFkappaB signaling. Anticancer Res. 35 (2015), 39–46.