title: Myristica fragrans Suppresses Tumor Growth and Metabolism by Inhibiting Lactate Dehydrogenase A.
abstract: Most cancer cells predominantly produce ATP by maintaining a high rate of lactate fermentation, rather than by maintaining a comparatively low rate of tricarboxylic acid cycle, i.e., Warburg's effect. In the pathway, the pyruvate produced by glycolysis is converted to lactic acid by lactate dehydrogenase (LDH). Here, we demonstrated that water extracts from the seeds of Myristica fragrans Houtt. (MF) inhibit the in vitro enzymatic activity of LDH. MF effectively suppressed cell growth and the overall Warburg effect in HT29 human colon cancer cells. Although the expression of LDH-A was not changed by MF, both lactate production and LDH activity were decreased in MF-treated cells under both normoxic and hypoxic conditions. In addition, intracellular ATP levels were also decreased by MF treatment, and the uptake of glucose was also reduced by MF treatment. Furthermore, the experiment on tumor growth in the in vivo mice model revealed that MF effectively reduced the growth of allotransplanted Lewis lung carcinoma cells. Taken together, these results suggest that MF effectively inhibits cancer growth and metabolism by inhibiting the activity of LDH, a major enzyme responsible for regulating cancer metabolism. These results implicate MF as a potential candidate for development into a novel drug against cancer through inhibition of LDH activity.
authors.affiliation: * Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Eun-Yeong
authors.initials: EY
authors.lastname: Kim
authors.affiliation: * Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: * Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Mi-Ju
authors.initials: MJ
authors.lastname: Park
authors.affiliation: † Department of Food Science and Technology, Keimyung University, Daegu, Republic of Korea.
authors.forename: Yeon-Seop
authors.initials: YS
authors.lastname: Jung
authors.affiliation: † Department of Food Science and Technology, Keimyung University, Daegu, Republic of Korea.
authors.forename: Syng-Ook
authors.initials: SO
authors.lastname: Lee
authors.affiliation: ‡ Department of Clinical Pathology, TaeKyeung University, Gyeongsan, Gyeongsangbuk-do, Republic of Korea.
authors.forename: Keuk-Jun
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: § Department of Life and Nanopharmaceutical Sciences and Department of Oriental Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Jung-Hye
authors.initials: JH
authors.lastname: Choi
authors.affiliation: * Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chung
authors.affiliation: * Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Ha
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D026323:Myristica / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism* / Q000503:physiopathology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012639:Seeds / Q000737:chemistry
chemical_list: D007527:Isoenzymes; D010936:Plant Extracts; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D005947:Glucose
keywords: Cancer Metabolism; Lactate Dehydrogenase; Myristica fragrans; Warburg Effect