Almeer R.S.Aref A.M.Hussein R.A.Othman M.S.Moneim A.E.A.Department of ZoologyCollege of ScienceKing Saud UniversityRiyadhSaudi Arabia; Faculty of BiotechnologyOctober University for Modern Science and Arts (MSA)GizaEgypt; Department of Zoology and EntomologyFaculty of ScienceHelwan UniversityCairoEgypt; Faculty of Preparatory yearUniversity of HailHailSaudi Arabia2020-01-092020-01-09201918715206https://doi.org/10.2174/1871520618666181116162441PubMedID30451117https://t.ly/1VVY7ScopusMSA Google ScholarBackground: 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). Result: 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. � 2019 Bentham Science Publishers.EnglishApoptosisBax/Bcl-2 ratioBerberineCinnamic acidEhrlich solid tumorantineoplastic agentberberinecinnamic acidcinnamic acid derivativemalonaldehydetumor markeranimalcell proliferationchemical structurechemistrydose responsedrug effectdrug screeningEhrlich ascites tumormalemouseoxidative stresspathologystructure activity relationAnimalsAntineoplastic AgentsBerberineBiomarkers, TumorCarcinoma, Ehrlich TumorCell ProliferationCinnamatesDose-Response Relationship, DrugDrug Screening Assays, AntitumorMaleMalondialdehydeMiceMolecular StructureOxidative StressStructure-Activity RelationshipArticlehttps://doi.org/10.2174/1871520618666181116162441PubMedID30451117