• Evaluation of the cytotoxic and apoptogenic effects of cinnamaldehyde and its effect on cytotoxicity and apoptosis induced by doxorubicin toward U87MG cells
  • Leila Hosseinzadeh,1,* Abbas Abbasi,2 Paricheher Yaghmaei,3
    1. Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
    2. Department of biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
    3. Department of biology, Science and Research Branch, Islamic Azad University, Tehran, Iran


  • Introduction: Glioblastoma is among the most aggressive cerebral tumors, with high incidence and mortality rates. Although the common medications may cause a slight increase in the median survival, they could be just palliative care for most of the patients and their tumors cannot be fully cured. Over the years, providing an adjuvant to chemotherapy has been the subject of various studies for enhancing the response rate to chemotherapy, reducing the side effects and minimizing the treatment resistance. Plants, as rich sources of bioactive compounds, could be promising alternatives or adjuvant for cancer chemotherapy. Cinnamaldehyde (CA) is an herbal-based compound widely used in traditional herbal medicine. It has been demonstrated that CA possesses in vitro anti-proliferative and pro-apoptotic effect on various cancer cell lines. In the present study, we tried for the first time to examine the possibility of co-administration of CA with Doxorubicin (DOX, as an anti-cancer drug) to glioblastoma cell, to potentiate the cytotoxic effect of this chemotherapy agent and overcome or reduce its side effects due to the herbal nature of CA.
  • Methods: Cellular toxicities of DOX and cinnamaldehyde were analyzed in U87MG cells using MTT method. The activity of caspase-3 and 9was determined by the Sigma colorimetric caspase-3 and 9 kit according to the manufacturer’s instructions.Mitochondrial membrane potential (MMP) was measured by using rhodamine 123 fluorescent dye. In order to examine the effect of CA on the expression of Bcl2 and Bax apoptotic gens, which participate in the mitochondrial apoptotic pathway, RT-PCR method was performed on the U87MG cells
  • Results: This study showed that CA significantly induced toxicity in U87MG cells, and also interestingly potentiated the toxicity of DOX toward U87MG cells. This indicates the synergistic interaction between DOX and CA, corroborating the successful role of CA in sensitizing glioblastoma cells to DOX as the promising chemotherapeutic agent for these tumor cells. The morphological study on cells before and after treatment with DOX and CA, alone or in combination, revealed the increase of cellular death and cell abnormalities such as shrinkage and vacuolization, upon treatment with CA. Research on caspases activity showed that CA was able to induce apoptosis in both intrinsic and extrinsic pathways. The results also indicated that CA increased the expression of both Bax and Bcl2 genes, but the increase of the Bax expression was more prominent.
  • Conclusion: According to the results of this study, it can be concluded that CA possesses the synergistic interactions with DOX, causing sensitizing U87MG cells to this chemotherapeutic drug. Collectively, these data suggest that CA must be introduced as a supplement effective in reducing cancer, and may have a promising role in enhancing the efficacy of DOX.
  • Keywords: Cinnamaldehyde, Herbal medicine, Glioblastoma, Cytotoxicity, Cancer