Rouhollahi Elham, Moghadamtousi Soheil Zorofchian, Al-Henhena Nawal, Kunasegaran Thubasni, Hasanpourghadi Mohadeseh, Looi Chung Yeng, Abd Malek Sri Nurestri, Awang Khalijah, Abdulla Mahmood Ameen, Mohamed Zahurin
Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
Drug Des Devel Ther. 2015 Jul 27;9:3911-22. doi: 10.2147/DDDT.S84560. eCollection 2015.
Curcuma purpurascens BI. rhizome, a member of the Zingiberaceae family, is a popular spice in Indonesia that is traditionally used in assorted remedies. Dichloromethane extract of C. purpurascens BI. rhizome (DECPR) has previously been shown to have an apoptosis-inducing effect on colon cancer cells. In the present study, we examined the potential of DECPR to prevent colon cancer development in rats treated with azoxymethane (AOM) (15 mg/kg) by determining the percentage inhibition in incidence of aberrant crypt foci (ACF). Starting from the day immediately after AOM treatment, three groups of rats were orally administered once a day for 2 months either 10% Tween 20 (5 mL/kg, cancer control), DECPR (250 mg/kg, low dose), or DECPR (500 mg/kg, high dose). Meanwhile, the control group was intraperitoneally injected with 5-fluorouracil (35 mg/kg) for 5 consecutive days. After euthanizing the rats, the number of ACF was enumerated in colon tissues. Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA) protein expressions were examined using immunohistochemical and Western blot analyses. Antioxidant enzymatic activity was measured in colon tissue homogenates and associated with malondialdehyde level. The percentage inhibition of ACF was 56.04% and 68.68% in the low- and high-dose DECPR-treated groups, respectively. The ACF inhibition in the treatment control group was 74.17%. Results revealed that DECPR exposure at both doses significantly decreased AOM-induced ACF formation, which was accompanied by reduced expression of PCNA. Upregulation of Bax and downregulation of Bcl-2 suggested the involvement of apoptosis in the chemopreventive effect of DECPR. In addition, the oxidative stress resulting from AOM treatment was significantly attenuated after administration of DECPR, which was shown by the elevated antioxidant enzymatic activity and reduced malondialdehyde level. Taken together, the present data clearly indicate that DECPR significantly inhibits ACF formation in AOM-treated rats and may offer protection against colon cancer development.
郁金(Curcuma purpurascens BI.)根茎是姜科植物的一种,是印度尼西亚一种受欢迎的香料,传统上用于各种疗法。郁金根茎的二氯甲烷提取物(DECPR)此前已被证明对结肠癌细胞具有诱导凋亡的作用。在本研究中,我们通过测定异常隐窝灶(ACF)发生率的抑制百分比,研究了DECPR预防用偶氮甲烷(AOM)(15 mg/kg)处理的大鼠结肠癌发生的潜力。从AOM处理后的第二天开始,三组大鼠每天口服一次,持续2个月,分别给予10%吐温20(5 mL/kg,癌症对照组)、DECPR(250 mg/kg,低剂量)或DECPR(500 mg/kg,高剂量)。同时,对照组连续5天腹腔注射5-氟尿嘧啶(35 mg/kg)。对大鼠实施安乐死后,在结肠组织中计数ACF的数量。使用免疫组织化学和蛋白质印迹分析检测Bax、Bcl-2和增殖细胞核抗原(PCNA)蛋白的表达。在结肠组织匀浆中测量抗氧化酶活性,并与丙二醛水平相关联。低剂量和高剂量DECPR处理组中ACF的抑制百分比分别为56.04%和68.68%。治疗对照组中ACF的抑制率为74.17%。结果显示,两种剂量的DECPR暴露均显著降低了AOM诱导的ACF形成,同时伴随着PCNA表达的降低。Bax的上调和Bcl-2的下调表明凋亡参与了DECPR的化学预防作用。此外,给予DECPR后,AOM处理引起的氧化应激显著减轻,这表现为抗氧化酶活性升高和丙二醛水平降低。综上所述,目前的数据清楚地表明,DECPR显著抑制AOM处理大鼠中ACF的形成,并可能提供对结肠癌发生的保护作用。