By Donnie Yance
Cancer isn’t merely uncontrolled cell growth, it’s a profound disruption of the body’s metabolic pathways. At its core, cancer represents a reprogramming of how cells generate, use, and store energy. This metabolic reprogramming is now recognized as a defining hallmark of cancer initiation, progression, and metastasis. Unlike healthy cells, which follow tightly regulated biochemical pathways to sustain balanced growth and repair, cancer cells hijack these pathways to fuel relentless proliferation. They shift their energy production away from normal mitochondrial respiration toward glycolysis, even in the presence of oxygen, a phenomenon known as the Warburg effect. Beyond this, cancer cells profoundly alter their metabolism of fatty acids, amino acids, and minerals to create a biochemical environment that supports survival, invasion, and immune evasion. Understanding these metabolic adaptations is essential not only for decoding the behavior of cancer but also for discovering new therapeutic strategies, especially those that can be found in nature’s medicinal treasure chest.
Metabolic reprogramming is a hallmark of cancer initiation, progression, and metastasis. The metabolic signature of cancer cells includes alterations in glycolysis, mitochondrial respiration, fatty acid, amino acid 1, and mineral (ion) metabolism.2
Normal Cell Metabolism vs. Cancer Cell Metabolism
Normal cell metabolism consists of controlled biochemical reactions (metabolic pathways) that maintain life. Healthy cells:
- Grow and divide only when necessary
- Undergo programmed cell death (apoptosis) when damaged
- Maintain cellular recycling processes (autophagy)
- Follow regulated signal transduction mechanisms
Autophagy and apoptosis are two important cellular processes with complex and intersecting protein networks.3 They maintain cellular homeostasis through signal transduction mechanisms 4 and are essential components of normal healthy cell metabolism.
In contrast, cancer cells:
- Exhibit uncontrolled cell growth and division leading to tumors
- Evade apoptosis
- Hijack metabolic pathways and essential nutrients 5
- Adapt through alternative metabolic mechanisms 6
Cancer cells create microenvironments characterized by poor oxygenation and high acidity. Their energy needs extend beyond glucose, involving significant alterations in free fatty acid turnover, oxidation, and clearance through tumor-produced lipid mobilizing factors.7
Why Cancer Cells Crave Fat
Cancer cells are hungry for fat, and understanding this appetite might help us fight the disease. For decades, scientists have known that cancer cells make and use fats differently than healthy cells. They produce more fats and use them in ways that help the cancer grow and spread.8
Lipid Metabolism Alterations in Cancer
Deregulated lipid metabolism has been demonstrated in many cancer settings. Cancer cells exploit various mechanisms to acquire lipids and rewire their metabolism: 9
- Modulating epigenetic enzymes that interact with lipid metabolism
- Using fatty acid oxidation for redox balancing
- Employing lipid droplets to sequester potentially toxic lipids
- Releasing lipid-rich extracellular vesicles
- Producing lipid signaling molecules involved in immune escape 10, 11 , 12, 13
Fatty acid synthase (FAS), the enzyme that converts carbohydrates to fatty acids, is essential for cancer growth. Blocking this enzyme results in cell death.14, 15, 16, 17 Tumors overexpressing FAS display more aggressive behavior. 18, 19, 20
Alteration in lipid metabolism is common in metastatic progression, including interaction between lipid metabolism and mitochondria in cancer development.21 For example, HER2-expressing breast cancer cells maintain invasiveness through persistent upregulation of lipid synthesis.22
Botanical and Dietary Compounds as Metabolic Targets
Several natural compounds can effectively target fatty acid metabolism in cancer:
Terpenoids and Flavonoids: Plant compounds that alleviate metabolic diseases by targeting lipid metabolism pathways. 23, 24, 25, 26
Key therapeutic compounds include:
- Resveratrol: Inhibits lipogenesis and induces apoptosis in cancer stem cells by decreasing FAS expression.27, 28, 29, 30 It causes cytotoxicity by inhibiting triglyceride accumulation.31
- Green Tea Catechins: Catechins, especially EGCG, inhibit FAS expression 32, 33, 34, 35 and downregulate fatty acid synthesis enzymes while inhibiting the PI3K/AKT/mTOR signaling pathway.36
- Quercetin: Acts as a potent inhibitor of lipogenesis in cancer cells through FAS inhibition. 37, 38, 39, 40, 41 It triggers FAS downregulation 42, 43 and reduces lipid accumulation.44
- Bitter Melon Extract: Suppresses oral cancer by inhibiting glycolysis and lipid metabolism pathways, reducing expression of key glycolytic genes.45 It also inhibits the c-Met signaling pathway in head and neck cancer 46 and functions as a natural AMPK activator. 47
- Salvia Miltiorrhiza Compounds: Cryptotanshinone (CPT) inhibits tumorigenesis by altering glutamine and lipid metabolism, affecting redox regulation and increasing reactive oxygen species production.48,49
- Diosgenin: Inhibits breast cancer stem cells by attenuating Wnt β-catenin signaling 50 and suppresses FAS expression in HER2-overexpressing breast cancer cells by modulating Akt, mTOR, and JNK phosphorylation.51
- Dandelion Extract: Inhibits triple-negative breast cancer cell proliferation by interfering with glycerophospholipid and unsaturated fatty acid metabolism through downregulating CHKA expression and inhibiting the PI3K/AKT/SREBP/FADS2 axis.52
- Gamma-Linolenic Acid (GLA): Found in borage seeds, exerts selective cytotoxic effects on cancer cells without affecting normal cells.53 GLA modulates inflammation 54, 55 and enhances the cytotoxicity of chemotherapy agents like docetaxel 56 and tamoxifen.57, 58
- Ginkgo Biloba Extract: Inhibits FAS activity and demonstrates cytotoxicity in cancer cells.59 Ginkgolic acid specifically inhibits FAS expression 60 and acts as a multi-target inhibitor of enzymes in pro-inflammatory lipid mediator biosynthesis. 61
Conclusion
As our understanding of cancer biology deepens, it becomes increasingly clear that lipid metabolism plays a central role in tumor growth, progression, and resistance to therapy. The abnormal fat-processing behaviors of cancer cells present promising therapeutic targets. By disrupting these altered pathways, we can weaken cancer’s metabolic foundation.
Botanical medicine, with its rich pharmacological diversity, offers a treasure trove of compounds that selectively target these pathways. From flavonoids like quercetin and catechins to terpenoids such as cryptotanshinone and diosgenin, nature provides effective tools to inhibit fatty acid synthase, modulate signaling cascades, and restore metabolic balance. These compounds not only demonstrate cytotoxic effects on cancer cells but often do so while protecting healthy cells and enhancing the effectiveness of conventional treatments.
By integrating these botanical strategies with the principles of unitive medicine and individualized care, we move closer to a comprehensive and holistic model of cancer therapy, one that addresses the metabolic roots of cancer and supports the body’s innate healing intelligence.
About the Author:
Donald R. Yance is the founder of the Mederi Center. A Clinical Master Herbalist and Certified Nutritionist, Donnie is renowned for his extraordinary knowledge and deep understanding of the healing properties of plants and nutrition, as well as of epigenetics, laboratory medicine, oncologic pathology, and molecular oncology. He is a professional member of the American Herbalists Guild, National Association of Nutrition Professionals, Academy of Integrative Health and Medicine, and the Society for Integrative Oncology.
References:
1. Srivastava A, Srivastava P, Mathur S, Abbas S, Rai N, Tiwari S, Tiwari M, Sharma L. Lipid Metabolism and Mitochondria: Cross Talk in Cancer. Curr Drug Targets. 2022;23(6):606-627. doi: 10.2174/1389450122666210824144907. PMID: 34431462.
2. Fnu G, Weber GF. Alterations of Ion Homeostasis in Cancer Metastasis: Implications for Treatment. Front Oncol. 2021 Dec 20;11:765329. doi: 10.3389/fonc.2021.765329. PMID: 34988012; PMCID: PMC8721045.
3. Mukhopadhyay S, Panda PK, Sinha N, Das DN, Bhutia SK. Autophagy and apoptosis: where do they meet? Apoptosis. 2014 Apr;19(4):555-66. doi: 10.1007/s10495-014-0967-2. PMID: 24415198.
4. Gupta R, Ambasta RK, Pravir Kumar. Autophagy and apoptosis cascade: which is more prominent in neuronal death? Cell Mol Life Sci. 2021 Dec;78(24):8001-8047. doi: 10.1007/s00018-021-04004-4. Epub 2021 Nov 6. PMID: 34741624.
5. H. Lee Moffitt Cancer Center & Research Institute. “How cancer cells ‘hijack’ a mechanism to grow.” ScienceDaily. ScienceDaily, 14 August 2012. <www.sciencedaily.com/releases/2012/08/120814100254.htm>.
6. Borden KLB. Cancer cells hijack RNA processing to rewrite the message. Biochem Soc Trans. 2022 Oct 31;50(5):1447-1456. doi: 10.1042/BST20220621. PMID: 36282006; PMCID: PMC9704515
7. Jin Z, Chai YD, Hu S. Fatty Acid Metabolism and Cancer. Adv Exp Med Biol. 2021;1280:231-241. doi: 10.1007/978-3-030-51652-9_16. PMID: 33791986.
8. Baenke F, Peck B, Miess H, Schulze A. Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development. Dis Model Mech. 2013 Nov;6(6):1353-63. doi: 10.1242/dmm.011338. PMID: 24203995; PMCID: PMC3820259.
9. Zhang C, Zhu N, Li H, Gong Y, Gu J, Shi Y, Liao D, Wang W, Dai A, Qin L. New dawn for cancer cell death: Emerging role of lipid metabolism. Mol Metab. 2022 Sep;63:101529. doi: 10.1016/j.molmet.2022.101529. Epub 2022 Jun 15. PMID: 35714911; PMCID: PMC9237930.
10. Bensaad K, Favaro E, Lewis CA, Peck B, Lord S, Collins JM, Pinnick KE, Wigfield S, Buffa FM, Li JL, Zhang Q, Wakelam MJO, Karpe F, Schulze A, Harris AL, Fatty acid uptake and lipid storage induced by HIF-1alpha contribute to cell growth and survival after hypoxia- reoxygenation, Cell Rep, 9 (2014) 349–365.
11. Butler LM, Perone Y, Dehairs J, Lupien LE, de Laat V, Talebi A, Loda M, Kinlaw WB, Swinnen JV. Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention. Adv Drug Deliv Rev. 2020;159:245-293. doi: 10.1016/j.addr.2020.07.013.
12. Bailey AP, Koster G, Guillermier C, Hirst EM, MacRae JI, Lechene CP, Postle AD, Gould AP, Antioxidant Role for Lipid Droplets in a Stem Cell Niche of Drosophila, Cell, 163 (2015) 340– 353
13. Butler LM, Perone Y, Dehairs J, Lupien LE, de Laat V, Talebi A, Loda M, Kinlaw WB, Swinnen JV. Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention. Adv Drug Deliv Rev. 2020;159:245-293. doi: 10.1016/j.addr.2020.07.013.
14. Menendez JA, Decker JP, Lupu R. In support of fatty acid synthase (FAS) as a metabolic oncogene: extracellular acidosis acts in an epigenetic fashion activating FAS gene expression in cancer cells. J Cell Biochem. 2005 Jan 1;94(1):1-4. doi: 10.1002/jcb.20310. PMID: 15523670
15. Ioachim HL, Decuseara R, Giancotti F, Dorsett BH. FAS and FAS-L expression by tumor cells and lymphocytes in breast carcinomas and their lymph node metastases. Pathol Res Pract. 2005;200(11-12):743-51. doi: 10.1016/j.prp.2004.09.006.
16. Tang Y, Zhou J, Hooi SC, Jiang YM, Lu GD. Fatty acid activation in carcinogenesis and cancer development: Essential roles of long-chain acyl-CoA synthetases. Oncol Lett. 2018 Aug;16(2):1390-1396. doi: 10.3892/ol.2018.8843. Epub 2018 May 30. PMID: 30008815; PMCID: PMC6036470.
17. Carvalho MA, Zecchin KG, Seguin F, Bastos DC, Agostini M, Rangel AL, Veiga SS, Raposo HF, Oliveira HCF, Loda M, et al. (2008). Fatty acid synthase inhibition with orlistat promotes apoptosis and reduces cell growth and lymph node metastasis in a mouse melanoma model. Int J Cancer. 123:2557–65.
18. Pflug BR, Pecher SM, Brink AW, Nelson JB, Foster BA. Increased fatty acid synthase expression and activity during progression of prostate cancer in the TRAMP model. Prostate. 2003 Nov 1;57(3):245-54. doi: 10.1002/pros.10297. PMID: 14518031.
19. Baron A, Migita T, Tang D, Loda M. Fatty acid synthase: a metabolic oncogene in prostate cancer? J Cell Biochem. 2004 Jan 1;91(1):47-53. doi: 10.1002/jcb.10708. PMID: 14689581.
20. Murata S, Yanagisawa K, Fukunaga K, Oda T, Kobayashi A, Sasaki R, Ohkohchi N. (2010). Fatty acid synthase inhibitor cerulenin suppresses liver metastasis of colon cancer in mice. Cancer Sci. 101:1861–5.
21. Srivastava A, Srivastava P, Mathur S, Abbas S, Rai N, Tiwari S, Tiwari M, Sharma L. Lipid Metabolism and Mitochondria: Cross Talk in Cancer. Curr Drug Targets. 2022;23(6):606-627. doi: 10.2174/1389450122666210824144907. PMID: 34431462.
22. Ravacci G.R., Brentani M.M., Tortelli T.C., Torrinhas R.S., Santos J.R., Logullo A.F., et al. Docosahexaenoic acid modulates a HER2-associated lipogenic phenotype, induces apoptosis, and increases trastuzumab action in HER2-overexpressing breast carcinoma cells. BioMed Research International. 2015;2015
23. Cheng C, Zhuo S, Zhang B, Zhao X, Liu Y, Liao C, Quan J, Li Z, Bode AM, Cao Y, Luo X. Treatment implications of natural compounds targeting lipid metabolism in nonalcoholic fatty liver disease, obesity and cancer. Int J Biol Sci. 2019 Jun 4;15(8):1654-1663. doi: 10.7150/ijbs.33837. PMID: 31360108; PMCID: PMC6643217.
24. Zhang C, Zhu N, Li H, Gong Y, Gu J, Shi Y, Liao D, Wang W, Dai A, Qin L. New dawn for cancer cell death: Emerging role of lipid metabolism. Mol Metab. 2022 Sep;63:101529. doi: 10.1016/j.molmet.2022.101529. Epub 2022 Jun 15. PMID: 35714911; PMCID: PMC9237930.
25. E E Mulvihill and M W Huff. Antiatherogenic properties of flavonoids: implications for cardiovascular health. Can J Cardiol; 2010. p. 26. Suppl A: 17A-21A.
26. Cheng C, Zhuo S, Zhang B, Zhao X, Liu Y, Liao C, Quan J, Li Z, Bode AM, Cao Y, Luo X. Treatment implications of natural compounds targeting lipid metabolism in nonalcoholic fatty liver disease, obesity and cancer. Int J Biol Sci. 2019 Jun 4;15(8):1654-1663. doi: 10.7150/ijbs.33837. PMID: 31360108; PMCID: PMC6643217.
27. Pandey PR, Okuda H, Watabe M, Pai SK, Liu W, Kobayashi A, Xing F, Fukuda K, Hirota S, Sugai T, Wakabayashi G, Koeda K, Kashiwaba M, Suzuki K, Chiba T, Endo M, Fujioka T, Tanji S, Mo YY, Cao D, Wilber AC, Watabe K. Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase. Breast Cancer Res Treat. 2011 Nov;130(2):387-98. doi: 10.1007/s10549-010-1300-6. Epub 2010 Dec 29. PMID: 21188630; PMCID: PMC3404809
28. Tian WX, Ma XF, Zhang SY, Sun YH, Li BH. (2011). Fatty acid synthase inhibitors from plants and their potential application in the prevention of metabolic syndrome. Clin Oncol Cancer Res. 8:1–9.
29. Pandey PR, Okuda H, Watabe M, Pai SK, Liu W, Kobayashi A, Xing F, Fukuda K, Hirota S, Sugai T, et al. (2011). Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase. Breast Cancer Res Treat. 130:387–98.
30. Pandey PR, Okuda H, Watabe M, Pai SK, Liu W, Kobayashi A, Xing F, Fukuda K, Hirota S, Sugai T, et al. (2011). Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase. Breast Cancer Res Treat. 130:387–98.
31. Rojas C, Pan-Castillo B, Valls C, Pujadas G, Garcia-Vallve S, Arola L, Mulero M. (2014). Resveratrol enhances palmitate- induced ER stress and apoptosis in cancer cells. Plos One. 9:e113929
32. Zeng YW, Yang JZ, Pu XY, Du J, Yang T, Yang SM, Zhu WH. (2013). Strategies of functional food for cancer prevention in human beings. Asian Pac J Cancer Prev. 14:585–592.
33. Wang S, Moustaid-Moussa N, Chen L, Mo H, Shastri A, Su R, Bapat P, Kwun I, Shen CL. (2014). Novel insights of dietary polyphenols and obesity. J Nutr Biochem. 25:1–18.
34. Ilze V, Alvaro MV, Josias HH. (2011). Natural products in anti-obesity therapy. Nat Prod Rep. 28:1493–533.
35. Tian WX. (2006). Inhibition of fatty acid synthase by polyphenols. Curr Med Chem. 13:967–77.
36. Chen L, Guo Y, Wu Z, Zhao S, Zhang Z, Zheng F, Sun L, Hao Z, Xu C, Wang T, Peng Y. Epicatechin gallate prevents the de novo synthesis of fatty acid and the migration of prostate cancer cells. Acta Biochim Biophys Sin (Shanghai). 2021 Dec 8;53(12):1662-1669. doi: 10.1093/abbs/gmab144. PMID: 34718375.
37. Lakhanpal P, Rai DK. Quercetin: a versatile flavonoid. Internet J Med Update. 2007;2(2):22–37
38. Vafadar A, Shabaninejad Z, Movahedpour A, Fallahi F, Taghavipour M, Ghasemi Y, Akbari M, Shafiee A, Hajighadimi S, Moradizarmehri S, Razi E, Savardashtaki A, Mirzaei H. Quercetin and cancer: new insights into its therapeutic effects on ovarian cancer cells. Cell Biosci. 2020 Mar 10;10:32. doi: 10.1186/s13578-020-00397-0. PMID: 32175075; PMCID: PMC7063794.
39. Vargas AJ, Burd R. Hormesis and synergy: pathways and mechanisms of quercetin in cancer prevention and management. Nutr Rev. 2010;68(7):418–428.
40. Vafadar A, Shabaninejad Z, Movahedpour A, Fallahi F, Taghavipour M, Ghasemi Y, Akbari M, Shafiee A, Hajighadimi S, Moradizarmehri S, Razi E, Savardashtaki A, Mirzaei H. Quercetin and cancer: new insights into its therapeutic effects on ovarian cancer cells. Cell Biosci. 2020 Mar 10;10:32. doi: 10.1186/s13578-020-00397-0. PMID: 32175075; PMCID: PMC7063794
41. Vafadar A, Shabaninejad Z, Movahedpour A, Fallahi F, Taghavipour M, Ghasemi Y, Akbari M, Shafiee A, Hajighadimi S, Moradizarmehri S, Razi E, Savardashtaki A, Mirzaei H. Quercetin and cancer: new insights into its therapeutic effects on ovarian cancer cells. Cell Biosci. 2020 Mar 10;10:32. doi: 10.1186/s13578-020-00397-0. PMID: 32175075; PMCID: PMC7063794
42. C Guzman, M Benet, S Pisonero-Vaquero. et al. The human liver fatty acid binding protein (FABP1) gene is activated by FOXA1 and PPARalpha; and repressed by C/EBPalpha: Implications in FABP1 down-regulation in nonalcoholic fatty liver disease. Biochim Biophys Acta. 2013;1831(4):803–18.
43. D Porras, E Nistal, S Martinez-Florez. et al. Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation. Free Radic Biol Med. 2017;102:188–202.
44. A K Stoldt, M Mielenz, G Nurnberg. et al. Effects of a six-week intraduodenal supplementation with quercetin on liver lipid metabolism and oxidative stress in peripartal dairy cows. J Anim Sci. 2016;94(5):1913–23
45. Sur S, Nakanishi H, Flaveny C, Ippolito JE, McHowat J, Ford DA, Ray RB. Inhibition of the key metabolic pathways, glycolysis and lipogenesis, of oral cancer by bitter melon extract. Cell Commun Signal. 2019 Oct 21;17(1):131. doi: 10.1186/s12964-019-0447-y. Erratum in: Cell Commun Signal. 2019 Nov 19;17(1):151.
46. Rajamoorthi A, Shrivastava S, Steele R, Nerurkar P, Gonzalez JG, Crawford S, Varvares M, Ray RB. Bitter Melon Reduces Head and Neck Squamous Cell Carcinoma Growth by Targeting c-Met Signaling. PLoS One. 2013 Oct 17;8(10):e78006. doi: 10.1371/journal.pone.0078006.
47. Yung MM, Ross FA, Hardie DG, Leung TH, Zhan J, Ngan HY, Chan DW. Bitter Melon (Momordica charantia) Extract Inhibits Tumorigenicity and Overcomes Cisplatin-Resistance in Ovarian Cancer Cells Through Targeting AMPK Signaling Cascade. Integr Cancer Ther. 2016 Sep;15(3):376-89. doi: 10.1177/1534735415611747. Epub 2015 Oct 19. PMID: 26487740; PMCID: PMC5689379.
48. Jiyoung Kim, Ki Won Lee, Hyong Joo Lee, Chapter 29 – Polyphenols Suppress and Modulate Inflammation: Possible Roles in Health and Disease, Editor(s): Ronald Ross Watson, Victor R. Preedy, Sherma Zibadi, Polyphenols in Human Health and Disease, Academic Press, 2014, Pages 393-408, ISBN 9780123984562, https://doi.org/10.1016/B978-0-12-398456-2.00029-3
49. Terado T, Kim CJ, Ushio A, Minami K, Tambe Y, Kageyama S, Kawauchi A, Tsunoda T, Shirasawa S, Tanaka H, Inoue H. Cryptotanshinone suppresses tumorigenesis by inhibiting lipogenesis and promoting reactive oxygen species production in KRAS-activated pancreatic cancer cells. Int J Oncol. 2022 Sep;61(3):108. doi: 10.3892/ijo.2022.5398. Epub 2022 Jul 27. PMID: 35894141; PMCID: PMC9339489.
50. Bhuvanalakshmi G, Basappa, Rangappa KS, Dharmarajan A, Sethi G, Kumar AP, Warrier S. Breast Cancer Stem-Like Cells Are Inhibited by Diosgenin, a Steroidal Saponin, by the Attenuation of the Wnt β-Catenin Signaling via the Wnt Antagonist Secreted Frizzled Related Protein-4. Front Pharmacol. 2017 Mar 20;8:124. doi: 10.3389/fphar.2017.00124. PMID: 28373842; PMCID: PMC5357646.
51. Chiang C-T, Way T-D, Tsai S-J, & Lin J-K. Diosgenin, a naturally occurring steroid, suppresses fatty acid synthase expression in HER2-overexpressing breast cancer cells through modulating Akt, mTOR and JNK phosphorylation, FEBS letters. 2007, vol. 581, no30, Pp. 5735-42.
52. Wang S, Hao HF, Jiao YN, Fu JL, Guo ZW, Guo Y, Yuan Y, Li PP, Han SY. Dandelion extract inhibits triple-negative breast cancer cell proliferation by interfering with glycerophospholipids and unsaturated fatty acids metabolism. Front Pharmacol. 2022 Sep 6;13:942996. doi: 10.3389/fphar.2022.942996. PMID: 36147318; PMCID: PMC9486077.
53. Mao JT, Xue B, Fan S, Neis P, Qualls C, Massie L, Fiehn O. Leucoselect Phytosome Modulates Serum Eicosapentaenoic Acid, Docosahexaenoic Acid, and Prostaglandin E3 in a Phase I Lung Cancer Chemoprevention Study. Cancer Prev Res (Phila). 2021 Jun;14(6):619-626. doi: 10.1158/1940-6207.CAPR-20-0585. Epub 2021 Mar 11. PMID: 33707173; PMCID: PMC8225569
54. Johnson MM, Swan DD, Surette ME, et al. Dietary supplementation with gamma-linolenic acid alters fatty acid content and eicosanoid production in healthy humans. J Nutr. 1997 Aug;127(8):1435-44.
55. Chang CS, Sun HL, Lii CK, Chen HW, Chen PY, Liu KL. Gamma-linolenic acid inhibits inflammatory responses by regulating NF-kappaB and AP-1 activation in lipopolysaccharide-induced RAW 264.7 macrophages. Inflammation. 2010 Feb;33(1):46-57
56. Menendez JA. Del Mar Barbacid M. Montero S. Sevilla E. Escrich E. Solanas M. Cortes-Funes H. Colomer R. R. Colomer, Division of Medical Oncology, Hospital Universitario 12 de Octubre, Avda. de Co[spacing acute]rdoba Km 5.4, E-28041 Madrid; Effects of gamma-linolenic acid and oleic acid on paclitaxel cytotoxicity in human breast cancer cells. European Journal of Cancer. Vol 37(3) (pp 402-413), 2001.
57. Kenny FS, Pinder SE, Ellis IO, Gee JM, Nicholson RI, Bryce RP, Robertson JF Gamma linolenic acid with tamoxifen as primary therapy in breast cancer, Int J Cancer 2000 Mar 1;85(5):643-8.
58. Robertson, John F. R. Gamma Linolenic Acid Accelerates Response to Tamoxifen in Breast Cancer February, 2001, Int J Cancer 2000;85:643-648.
59. Oh J, Hwang IH, Hong CE, Lyu SY, Na M. Inhibition of fatty acid synthase by ginkgolic acids from the leaves of Ginkgo biloba and their cytotoxic activity. J Enzyme Inhib Med Chem. 2013 Jun;28(3):565-8. doi: 10.3109/14756366.2012.658786. Epub 2012 Mar 1. PMID: 22380770.
60. Oh J, Hwang IH, Hong CE, Lyu SY, Na M. (2013). Inhibition of fatty acid synthase by ginkgolic acids from the leaves of Ginkgo biloba and their cytotoxic activity. J Enzyme Inhib Med Chem. 28:565–8.
61. Gerstmeier J, Seegers J, Witt F, Waltenberger B, Temml V, Rollinger JM, Stuppner H, Koeberle A, Schuster D, Werz O. Ginkgolic Acid is a Multi-Target Inhibitor of Key Enzymes in Pro-Inflammatory Lipid Mediator Biosynthesis. Front Pharmacol. 2019 Jul 17;10:797. doi: 10.3389/fphar.2019.00797. PMID: 31379572; PMCID: PMC6650749.