Doxorubicin has been used to treating cancers, including breast cancer, bladder cancer, and acute lymphocytic leukemia, however, few studies have investigated its anti-inflammatory activity. In this study, we used mouse spleen cells treated with lipopolysaccharide (LPS), a representative inflammatory agent to investigate the effects of doxorubicin. Specially, we investigated the effects of doxorubicin on metabolic activity, cell size, cell death, and cytokine production of LPS-treated spleen cells. Doxorubicin significantly decreased the metabolic activity, even when applied at relatively low concentrations (1.6-8 ng/mL). To investigate the potential mechanism, we measured the mitochondrial membrane potential (MMP) of the LPS-treated spleen cells using Rhodamine 123. Doxorubicin decreased MMP and cell size, and induced cell death. Furthermore, doxorubicin suppressed the production of tumor necrosis factor (TNF)-alpha, a representative cytokine, in LPS-treated spleen cells. Taken together, doxorubicin decreased metabolic activity and the production of inflammatory cytokines, while increasing the death of LPS-induced hyperactivated spleen cells. This results will enable broader application of doxorubicin, as an anti-inflammatory agent, in clinical and research fields.

Breast cancer is of enormous concern worldwide and linked with age, sex, hormonal factors, and family history. The treatment of early breast cancer includes treating the disease locally with surgery, radiation therapy, or both and treating microscopic systemic disease with either one or a combination of chemotherapy, endocrine therapy, or biologic therapy. Doxorubicin is a well-known anthracycline antibiotic and antineoplastic drug usually administered to breast cancer patients. However, there have been some reports suggesting that doxorubicin causes side effects such as cardiotoxicity. Furthermore, breast cancer patients on doxorubicin treatment are commonly prescribed steroid suppression therapy. In addition, it has been previously reported that lack of estrogen elevates cardiotoxicity. In this study, we evaluated whether the steroid suppression therapy might influence the cardiotoxicity of doxorubicin. We hypothesized that the presence of a steroid hormone, particularly estrogen, is closely related to doxorubicin action. To investigate the effect of estrogen, mice were divided into four groups: control group, doxorubicin-treated group, ovariectomized group, and ovariectomized plus doxorubicin-treated group. We observed upregulation of inflammatory cytokine gene and downregulation of apoptotic genes in the groups treated with doxorubicin, particularly in the ovariectomized plus doxorubicin-treated group. This suggests that administration of doxorubicin under a non-steroid condition can excessively damage the heart. In summary, combination treatment of hormonal and doxorubicin therapy for breast or many different types of cancer patients must be prescribed with requisite precautions.

Stimuli-responsive biomaterials that alter their function through sensing local molecular cues may enable technological advances in the fields of drug delivery, gene delivery, actuators, biosensors, and tissue engineering. In this research, pH-responsive hydrogel which is comprised of dimethylaminoethyl methacylate (DMAEMA) and 2-hydroxyethyl methacrylate (HEMA) was synthesized for the effective delivery of doxorubicin (Dox) to breast cancer cells. Cancer and tumor tissues show a lower extracellular pH than normal tissues. DMAEMA/HEMA hydrogels showed significant sensitivity by small pH changes and each formulation of hydrogels was examined by scanning electron microscopy, mechanical test, equilibrium mass swelling, controlled Dox release, and cytotoxicity. High swelling ratios and Dox release were obtained at low pH buffer condition, low cross-linker concentration, and high content of DMAEMA. Dox release was accelerated to 67.3% at pH 5.5 for 6-h incubation at 37oC, while it was limited to 13.8% at pH7.4 at the same time and temperature. Cell toxicity results to breast cancer cells indicate that pH-responsive DMAEMA/HEMA hydrogels may be used as an efficient matrix for anti-cancer drug delivery with various transporting manners. Also, pH-responsive DMAEMA/HEMA hydrogels may be useful in therapeutic treatment which is required a triggered release at low pH range such as gene delivery, ischemia, and diabetic ketoacidosis.

Doxorubicin, a widely used chemotherapeutic agent, were found rapidly undergo morphological and biochemical changes via discrete effector signaling pathways consistent with the occurrence of apoptosis of oocyte, and a little known is actions of this drug in early embryos. Poly (ADP-ribose) polymerase (PARP), a DNA repair enzyme, also plays the important role during the apoptosis of cell. The cleavage of PARP by caspase-3 inactivates it and inhibits PARP's DNA-repairing abilities. Cleaved PARP (cPARP) can be a marker of apoptosis.Doxorubicin inhibited the early embryo development, but the treatment could still reach the BL (blastocyst) stagethat suggested that involved in DNA synthesis and repaired progress. Herein, the higher expression of PARP family shown especially in 2, 4 cell stagy. There was evidence of expression of Caspase3 and Bcl2l1 during embryogenesis (2 cell, 4 cell, morula and BL stage), suggesting that modulationsof apoptosis-related genes and PARP were cause by DXR. Furthermore, the effect of doxorubicin on early embryo development was assessed different stage rates, and apoptosis index also conformed doxorubicin modulate embryo development by regulating apoptosis- related genes and PARP family genes. In conclusion, Doxorubicin blocked pre- implantation development in early mouse embryos by altering apoptosis-related gene expression and inactivating DNA repair by Parp.

Doxorubicin, a widely used chemotherapeutic agent, were found rapidly undergo morphological and biochemical changes via discrete effector signaling pathways consistent with the occurrence of apoptosis of oocyte. In this report, we elucidated the molecular requirements for actions of this drug in early embryos. Poly (ADP-ribose) polymerase (PARP), a DNA repair enzyme, and its homologues have recently been shown in female oocyte cells. However, the cleavage of PARP by caspase-3 inactivates it and inhibits PARP's DNA-repairing abilities. Cleaved PARP (cPARP) may be considered a marker of apoptosis. Doxorubicin inhibited the early embryo development, but the treatment could still reach the BL (blastocyst) stage that suggested that involved in DNA synthesis and repaired progress. Herein, the higher expression of PARP family shown especially in 2, 4 cell stagy. There was evidence of expression of Caspase3 and Bcl2l1 during embryogenesis (2 cell, 4 cell, morula and BL stage), suggesting that modulations of apoptosis-related genes and PARP were cause by DXR. Furthermore, the effect of doxorubicin on early embryo development was assessed different stage rates, and apoptosis index also conformed doxorubicin modulate embryo development by regulating apoptosis-related genes and PARP family genes. In conclusion, Doxorubicin blocked pre-implantation development in early mouse embryos by altering apoptosis-related gene expression and inactivating DNA repair by Parp.

Doxorubicin is a anti-cancer drugs that interferes with the growth and spread of cancer cells in human body. Doxorubicin is used to treat different types of cancers that affect the ovary, thyoid and lungs, but induced side effect such as nephrotoxicity and cardiotoxicity. Thus, we investigated that the effect of iridin on doxorubicin-induced necrosis in HK-2 cells, a human proximal tubule cell. To confirm effect of iridin on doxorubicin-induced necrosis, HK-2 cells are treated with 10 μM doxorubicin and 80 μM iridin. 80 μM iridin reduced 10 μM doxorubicin-induced necrosis, the mitochondrial over activation and caspase-3 activation. However, iridin reduces anti-cancer effect of doxorubicin such as PARP1 and caspase-3 activation, checkpoint proteins (CDK4 and CDK6) in NCI-H1129 cells (Human non-small cell lung cancer cell). In HCT-116 cells (Human colorectan cancer cell), iridin do not increased protein expression of CDK4 and CDK6 decreased by doxorubicin. Results indicate that treatment of iridin was diminished doxorubicin-induced necrosis in HK-2 cells. However, iridin was decreased anti-cancer effect of doxorubicin on NCI-H1229, but not HCT-116. Thus, further experiment are required to iridin treatment on various cancer cells and animal models because effect of iridin different cell type.

Background: Cynaroside is a flavone, a flavonoid-like compound, known by different names (luteoloside and cinaroside). It is commonly found in Lonicera japonica Thunb., Chrysanthemum moriflium, and Angelica keiskei. The process of cell death has been classified as necrosis and apoptosis. Necrosis refers to unregulated cell death induced by a chemotherapeutic agent. Doxorubicin is an anthracycline anti-cancer drug used to treat acute leukemia, cancer, and lymphoma. However, it induces nephrotoxicity including tubular damage. Therefore, we investigated the protective effect of cynaroside against doxorubicin-induced necrosis in HK-2 cells. Methods and Results: To confirm the beneficial effect of cynaroside on doxorubicin-induced necrosis, HK-2 cells, a human proximal tubule epithelial cell line were treated with 10 μM doxorubicin and 80 μM cynaroside. Doxorubicin treatment resulted in increased DNA fragmentation, caspase-3 activity and mitochondria hyperactivation during cell necrosis. However, pretreatment with 80 μM cynaroside attenuated DNA fragmentation, caspase-3 activity and mitochondria hyperactivation induced by 10 μM doxorubicin in HK-2 cells. Conclusions: These results indicated that pretreatment with cynaroside ameliorated doxorubicin-induced necrosis in HK-2 cells. Therefore, cynaroside be used as a therapeutic agent for improving doxorubicin-induced nephrotoxicity. However, further studies are required to evaluated the toxicity of cynaroside treatment in animals and to determine its protective effect against doxorubicininduced nephrotoxicity in an animal model.

Chemoresistance is one of the main problems to treat different kinds of cancers or cancer cells. Therefore, it is necessary to find out the strategies to make the cancer cells sensitive to chemotherapy along with optimal dosage of drugs. We examined sensitivity of MCF7 cells through pretreating with an epigenetic modulator, azacytidine (AzaC) to doxorubicin (Dox). The cells were treated with 5 and 10 mM of AzaC for a week, subsequently with 50, 100 and 500 nM of doxorubicin for 24 and 48h. It was found that pretreatment of AzaC significantly enhance the sensitivity of MCF7 cells to Dox, inducing cell death. After 24h 15% cells underwent apoptosis in 500 nM dox treatment group while 23.4% cells death occurred in AzaC pre treatment group. After 48h MCF7 cells treated with Dox showed 19.0% cell death while AzaC sensitized cells showed 50.0% cells death when exposed to 500 nM of Dox for 48h. Western blot analysis showed the upregulations in the expression of bax, caspase-3, caspase-9 and p53 in AzaC-sensitized MCF7 cells treated with Dox as compared to those treated with only Dox. There was no clear indication for pro-apoptosis genes in the cells treated with individual drugs. These results showed that pretreatment with the epigenetic modulator significantly increased the sensitivity of MCF7 cells to Dox. Therefore it is concluded that demethylation event might enhance the activity of DNA intercalating agents to induce DNA damage in breast cancer cells.