Myristica fragransSuppresses 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.

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“…The results showed as a potential candidate for the development into a novel drug against cancer through inhibition of lactate dehydrogenase activity. [78] A study of myrislignan on A549 cells in vitro and in vivo reveal a potential mechanism for the anticancer effect of myrislignan on human lung cancer, while suggesting that myrislignan may be a capable compound for the management of lung cancer. [79] …”

“…Antibacterial activity [62][63][64][65][66][67] Trimyristin and myristic acid, [66] macelignan [67] Insecticidal and repellent activity [64,68] Essential oil [64] Antiamebic activity [69,70] Essential oil [70] Antifungal activity [64,72] Lignans-EA6, MDA and NB, [71] sabinene, terpinen-4-ol, safrole, α-pinene, β-phellandrene, and γ-terpinene [64] Hypolipidemic activity [73] Ethanolic extract [73] Antioxidant activity [60,74,75] Eugenol [74] Anticancer activity [76][77][78][79] Myrislignan [79] Aphrodisiac activity [80,81] Ethanolic extract [80,81] Anxiogenic, analgesic and sedative activities [82,83] N-hexane extract and trimyristin [82] Antidepressant activity [84] N-hexane extract [84] Anti-inflammatory activity [85,86] 8-O-4' type neolignans, named myrifralignan A-E (1-5) [85] Hepatoprotective activity [87,88] Myristicin, [87] macelignan [88]...…”

Anticancer Study of Myristica Fragrans Houtt. (Mace) Extract on 4-Nitroquinoline-1-Oxide-Induced Oral Cancer in Rats

“…(family: Myristicaceae), an evergreen aromatic tree cultivated in many tropical countries, and is widely used as a spice and also to flavor many kinds of baked foods and vegetables [7]. Mace composed of a maximum number of plant constituents mainly alkyl benzene derivatives (myristicin, elemicin, safrole, etc.…”

“…Mace composed of a maximum number of plant constituents mainly alkyl benzene derivatives (myristicin, elemicin, safrole, etc. ), terpenes, alpha-pinene, beta-pinene, myristic acid, trimyristin, neolignan (myrislignan), and mace lignin [7]. The chemical constituents of mace have been investigated by scientists for hypolipidemic, hypocholesterolemic, antimicrobial, antidepressant, aphrodisiac, memory-enhancing, antioxidant, and hepatoprotective properties [8].…”

“…Mace is widely used as a flavoring agent, a hair dye, and a folk medicine. It also possesses anti-papilloma genic, anticarcinogenic, chemopreventive, and anti-inflammatory activities [7,9]. In dentistry application, macelignan, an active compound from M. fragrans Houtt., had strong anticarcinogenic activity and antibacterial effect [8].…”