二十二碳六烯酸於提升粒線體功能及調節能量代謝狀況降低前列腺癌細胞之存活

Docosahexaenoic acid decreases prostate cancer cell survival in condition of enhanced mitochondrial function and modulated energy metabolism

吳欣茹(Sin-Ru Wu)

指導教授 ： 謝榮鴻

臺北醫學大學/公共衛生暨營養學院/保健營養學研究所/碩士(2013年)

摘要

德國生化學家 Warburg 於1930年指出粒線體功能缺陷可能與癌症的發生有關，可能是造成腫瘤細胞糖解作用增加的原因。本研究探討介入二十二碳六烯酸 (docosahexaenoic acid, DHA)於前列腺癌 LNCaP 細胞，探討是否影響粒線體功能及能量代謝情形而影響前列腺癌細胞生長。LNCaP 細胞介入 DHA 後24、48及72小時之後測量細胞存活率、粒線體膜脂質組成、ATP 生成量、粒線體酵素活性、粒線體膜電位、粒線體 DNA套數以及活性氧屬 (reactive oxygen species, ROS)生成情形。結果顯示 DHA 介入不只降低癌細胞存活率也可進入細胞改變粒線體膜脂質組成，並且提高粒線體酵素 NCCR (nicotinamide adenine dinucleotide (NADH)-cytochrome c reductase)及 SCCR (succinate-cytochrome c reductase)之活性、增加粒線體氧消耗速率、粒線體膜電位以及增加 ROS 產生。但 ATP 產生並未隨著粒線體活性增加而增加，相反地，降低其 ATP 產生。本實驗中，DHA 可提升粒線體酵素活性、增加粒線體氧消耗速率、膜電位以及 ROS 產生，促進粒線體生合成及功能時，未見伴隨 ATP 產生能力增加，相反地，過多的 ROS 產生超過能量釋出最終導致癌細胞死亡。

關鍵字

粒線體 ； 二十二碳六烯酸 ； 前列腺癌 ； 活性氧屬 ； 粒線體生合成

並列摘要

In the 1930s, Dr. Warburg indicated that mitochondrial dysfunction could be related to the occurrence of cancer, hence the reason for the increased glycolysis in tumor cells. This current study investigates the effects of docosahexaenoic acid (DHA) on mitochondrial function and energy metabolism in LNCaP prostate cancer cells and, explored the potential of DHA intervention in growth of prostate cancer cells. LNCaP cells were treated with DHA and cell viability, mitochondrial membrane lipid composition, ATP generation, mitochondrial enzyme activity, mitochondrial membrane potential, mitochondrial DNA copy number and reactive oxygen species (ROS) were analyzed after 24, 48 or 72 hours. The results show that the DHA intervention reduced the survival of cancer cells and altered the mitochondrial membrane lipid composition. DHA improved mitochondrial enzyme nicotinamide adenine dinucleotide (NADH)-cytochrome c reductase (NCCR) and succinate-cytochrome c reductase (SCCR) activities, and increased mitochondrial oxygen consumption rate (OCR). DHA also increased mitochondrial membrane potential and ROS levels. In contrast to enhanced mitochondrial activities after DHA treatment, increased ATP production was not observed. In conclusion, DHA treatment increased mitochondrial enzyme activities, the rate of mitochondrial oxygen consumption, increased mitochondrial membrane potential, mitochondrial biogenesis and ROS generation. However, DHA could not increase ATP production in their more mitochondria content. In contract, more ROS than energy release which partially could eventually leading to death of cancer cells.

並列關鍵字

mitochondria ； DHA ； prostate cancer cells ； ROS ； mitochondrial biogenesis

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