Evaluation of the Effect of Crocin on Doxorubicin-Induced Cardiotoxicity.

Despite newer advances in cancer treatment, chemotherapy is still one of the most widely used treatment strategies in this field. However, this treatment strategy faces major challenges. Doxorubicin (Dox) is an effective chemotherapeutic agent used to treat various cancers. However, several studies have shown that the use of Dox in therapeutic concentrations is associated with serious side effects, such as cardiac toxicity. The use of natural products in combination with chemotherapeutic agents to reduce side effects is a novel approach, and several studies have shown promising results. In this regard, we examined the effect of Crocin on doxorubicin-induced cardiotoxicity in rat and H9c2 cell line. The in vitro model on H9C2 cells and the in vivo models on rats were treated with doxorubicin. Cell viability, DNA damage, and apoptosis were measured in H9C2 cell line in the presence and absence of Crocin. Oxidative stress and various inflammatory parameters, as well as cardiac function tests, also were assessed in doxorubicin-induced cardiotoxicity animal model in the presence and absence of Crocin. Our results showed that Crocin can significantly decrease apoptosis in H9C2 cell line through a reduction in ROS production and DNA damages. Moreover, evaluation of the effect of Crocin on doxorubicin-induced cardiotoxicity animal model showed that Crocin also can significantly reduce oxidative stress and inflammatory parameters in the serum of the animals. Assessment of cardiac function revealed that Crocin has a significant protective effect against doxorubicin-induced cardiotoxicity in the animal model. Our data indicate that Crocin significantly attenuated doxorubicin-induced cardiotoxicity. Hence, Crocin could be potentially used as an adjuvant treatment in combination with Dox to reduce cardiotoxicity.

Fractionated radiation promotes proliferation and radioresistance in bystander A549 cells but not in bystander HT29 cells.

AIMS: Recent studies suggest that direct exposure of cells to fractionated radiotherapy might induce radioresistance. However, the effects of fractionated radiotherapy on the non-irradiated bystander cells remain unclear. We hypothesized that fractionated radiotherapy could enhance radioresistance and proliferation of bystander cells. MAIN METHODS: Human tumor cell lines, including A549 and HT29 were irradiated (2 Gy per day). The irradiated cells (either A549 or HT29) were co-cultured with non-irradiated cells of the same line using transwell co-culture system. Tumor cell proliferation, radioresistance and apoptosis were measured using MTT assay, clonogenic survival assay and Annexin-V in bystander cells, respectively. In addition, activation of Chk1 (Ser 317), Chk2 (Thr 68) and Akt (Ser473) were measured via western blot. KEY FINDINGS: Irradiated HT29 cells induced conventional bystander effects detected as modulation of clonogenic survival parameters (decreased area under curve, D10 and ED50 and increased α) and proliferation in recipient neighbors. While, irradiated A549 cells significantly enhanced the radioresistance and proliferation of bystander cells. These changes were accompanied with enhanced activation of Chk1, Chk2 and Akt in non-irradiated bystander A549 cells. Moreover, both bystander effects (damaging and protective) were mediated through secreted factors. SIGNIFICANCE: These findings suggest that fractionated radiotherapy could promote proliferation and radioresistance of bystander cells probably through survival and proliferation pathways.