小檗碱和肉桂酸对艾氏腹水癌小鼠的抗肿瘤作用。
Antitumor Potential of Berberine and Cinnamic Acid against Solid Ehrlich Carcinoma in Mice.
机构信息
Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
Faculty of Biotechnology, October University for Modern Science and Arts (MSA), Giza, Egypt.
出版信息
Anticancer Agents Med Chem. 2019;19(3):356-364. doi: 10.2174/1871520618666181116162441.
BACKGROUND
Berberine and cinnamic acid are natural compounds that exhibit potent anticancer activities through distinct molecular mechanisms.
OBJECTIVE
In the present study, we aimed to investigate the proapoptotic potential of cinnamic acid and berberine in cancer cells by examining their effect on the expression of proapoptotic and antiapoptotic genes. Moreover, the effects of berberine and cinnamic acid on the antitumor activity of cisplatin were investigated in Ehrlich solid tumor-bearing mice.
METHODS
For the study, 90 male mice were inoculated intramuscularly with Ehrlich ascites tumor cells (2.5 × 106/mouse), and then on day 4, mice were randomly divided into six experimental groups (group 1-untreated Ehrlich solid tumor (EST), group 2-EST treated CDDP, group 3-EST treated CA, group 4-EST treated BER, group 5-EST treated CA + CDDP, and group 6-EST treated BER + CDDP).
RESULTS
The results showed that berberine and cinnamic acid significantly decreased tumor growth and tumor volume (-74.8 and -75.5%, respectively) both as single agents and in combination with cisplatin. Moreover, both berberine and cinnamic acid increased the ratio of tumor growth inhibition (-91.5 and -92.6%, respectively), mean survival time (61.5 and 26 days, respectively), and percentage increase in lifespan (559 and 263%, respectively) of the treated mice. Our results also showed that both berberine and cinnamic acid-induced apoptosis by increasing the Bax/Bcl-2 ratio (74.1 and 45.1, respectively) and caspase-3 expression (14.3- and 11.6-fold increase, respectively). Additionally, berberine and cinnamic acid decreased oxidative stress markers, as shown by the decrease in lipid peroxidation and nitric oxide levels and an increase in reduced glutathione level.
CONCLUSION
These results suggest that berberine and cinnamic acid have potential as antitumor and antioxidant agents derived from natural sources, which could be used alone or in combination with regular chemotherapeutic agents, such as cisplatin. These effects could be attributed to the proapoptotic activity of berberine and cinnamic acid.
背景
小檗碱和肉桂酸是两种天然化合物，它们通过不同的分子机制表现出强大的抗癌活性。
目的
本研究旨在通过检测促凋亡和抗凋亡基因的表达，研究肉桂酸和小檗碱在癌细胞中的促凋亡潜力。此外，还研究了小檗碱和肉桂酸对顺铂在艾氏腹水瘤荷瘤小鼠中的抗肿瘤活性的影响。
方法
为了进行这项研究，90 只雄性小鼠肌肉内接种艾氏腹水瘤细胞（2.5×106/只），然后在第 4 天，小鼠随机分为六组实验（第 1 组-未处理的艾氏实体瘤（EST），第 2 组-EST 用 CDDP 处理，第 3 组-EST 用 CA 处理，第 4 组-EST 用 BER 处理，第 5 组-EST 用 CA+CDDP 处理，第 6 组-EST 用 BER+CDDP 处理）。
结果
结果表明，小檗碱和肉桂酸单独或联合顺铂均显著抑制肿瘤生长和肿瘤体积（分别减少 74.8%和 75.5%）。此外，小檗碱和肉桂酸均增加了肿瘤生长抑制率（分别增加 91.5%和 92.6%）、平均存活时间（分别为 61.5 和 26 天）和寿命延长率（分别增加 559%和 263%）。我们的结果还表明，小檗碱和肉桂酸通过增加 Bax/Bcl-2 比值（分别增加 74.1%和 45.1%）和 caspase-3 表达（分别增加 14.3-和 11.6 倍）诱导细胞凋亡。此外，小檗碱和肉桂酸降低了脂质过氧化和一氧化氮水平，同时增加了还原型谷胱甘肽水平，从而降低了氧化应激标志物。
结论
这些结果表明，小檗碱和肉桂酸具有作为来源于天然来源的抗肿瘤和抗氧化剂的潜力，可单独或与顺铂等常规化疗药物联合使用。这些作用可能归因于小檗碱和肉桂酸的促凋亡活性。
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