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Antitumor Potential of Berberine and Cinnamic Acid against Solid Ehrlich Carcinoma in Mice
Rafa S Almeer1, Ahmed M Aref2, Romisa A Hussein3
1Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
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.
Insights
Berberine and cinnamic acid show significant antitumor effects by inducing apoptosis and reducing tumor growth. These natural compounds enhance cisplatin
Area of Science:
- Natural product chemistry
- Cancer biology
- Pharmacology
Background:
- Berberine and cinnamic acid are natural compounds with known anticancer properties.
- Their distinct molecular mechanisms contribute to their therapeutic potential.
Purpose of the Study:
- To investigate the proapoptotic effects of cinnamic acid and berberine on cancer cells.
- To evaluate their impact on proapoptotic and antiapoptotic gene expression.
- To assess the combined antitumor activity of these compounds with cisplatin in a mouse model.
Main Methods:
- Ehrlich solid tumor (EST) model established in 90 male mice.
- Mice were divided into six groups, including untreated, cisplatin (CDDP)-treated, cinnamic acid (CA)-treated, berberine (BER)-treated, and combinations with CDDP.
- Tumor growth, volume, survival time, and oxidative stress markers were analyzed.
Main Results:
- Berberine and cinnamic acid significantly reduced tumor growth and volume, both alone and with cisplatin.
- Both compounds increased tumor growth inhibition, mean survival time, and lifespan percentage.
- Apoptosis was induced by increasing the Bax/Bcl-2 ratio and caspase-3 expression, while oxidative stress markers decreased.
Conclusions:
- Berberine and cinnamic acid demonstrate potential as natural antitumor and antioxidant agents.
- They can be used as standalone therapies or in combination with chemotherapy (e.g., cisplatin).
- Proapoptotic activity is a key mechanism underlying their observed effects.
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