Potential enhancement of host immunity and anti-tumor efficacy of nanoscale curcumin and resveratrol in colorectal cancers by modulated electro- hyperthermia

Abstract

Background Modulated electro-hyperthermia (mEHT) is a form of hyperthermia used in cancer treatment. mEHT has demonstrated the ability to activate host immunity by inducing the release of heat shock proteins, triggering apoptosis, and destroying the integrity of cell membranes to enhance cellular uptake of chemo-drugs in tumor cells. Both curcumin and resveratrol are phytochemicals that function as effective antioxidants, immune activators, and potential inhibitors of tumor development. However, poor bioavailability is a major obstacle for use in clinical cancer treatment. Methods This purpose of this study was to investigate whether mEHT can increase anti-cancer efficacy of nanosized curcumin and resveratrol in in vitro and in vivo models. The in vitro study included cell proliferation assay, cell cycle, and apoptosis analysis. Serum concentration was analyzed for the absorption of curcumin and resveratrol in SD rat model. The in vivo CT26/BALB/c animal tumor model was used for validating the safety, tumor growth curve, and immune cell infiltration within tumor tissues after combined mEHT/curcumin/resveratrol treatment. Results The results indicate co-treatment of mEHT with nano-curcumin and resveratrol significantly induced cell cycle arrest and apoptosis of CT26 cells. The serum concentrations of curcumin and resveratrol were significantly elevated when mEHT was applied. The combination also inhibited the growth of CT26 colon cancer by inducing apoptosis and HSP70 expression of tumor cells while recruiting CD3+ T-cells and F4/80+ macrophages. Conclusions The results of this study have suggested that this natural, non-toxic compound can be an effective anti-tumor strategy for clinical cancer therapy. mEHT can enable cellular uptake of potential anti-tumor materials and create a favorable tumor microenvironment for an immunological chain reaction that improves the success of combined treatments of curcumin and resveratrol.

Recent Advancements on Immunomodulatory Mechanisms of Resveratrol in Tumor Microenvironment

“…Further, in the combined treatment group, Hsp70 (heat shock protein 70) was found to be overexpressed. This study supported the idea of HSP-mediated recruiting of antigen-presenting cells (APC) since significantly higher T-lymphocyte and macrophage infiltration were found after mEHT with curcumin and resveratrol treatment [ 61 ].…”

“…This cartoon summarizes the effects of resveratrol on specific immune cells. CTLs: cytotoxic T-cells; DCs: dendritic cells [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]; Tregs: regulatory T-cells; TAMs: tumor-associated macrophages [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ]; NK: natural killer cells [ 62 , 63 , 64 , 65 , 66 ]. Visualization created with .…”

Resveratrol and its Nanoparticle suppress Doxorubicin/Docetaxel-resistant anaplastic Thyroid Cancer Cells in vitro and in vivo

“…For this reason, nano drug delivery system was employed here as the carrier to encapsulate resveratrol. By this way, resveratrol can be protected from being metabolized by intrinsic biological enzymes 58 and released slowly to neutral environment in vivo 59 . Human IL-13Rα2, a 380 amino acid glycoprotein located on the plasma membrane, activates tumor related signaling molecules such as PI3K, ATK and SRC to promote tumor progression 60 , 61 .…”

Dietary Polyphenols: Promising Adjuvants for Colorectal Cancer Therapies

“…Moreover, one of the combinations tested was also effective at suppressing colonosphere formation [ 70 ]. In mice implanted with CT26 tumor cells, oral administration of a nano-formulation of curcumin and resveratrol (300 mg/kg every 2 days for 2 weeks) in combination with modulated electro-hyperthermia (mEHT) treatment significantly suppressed tumor growth and triggered host immunity by recruiting T cells and F4/80+ macrophages into the tumor mass [ 71 ].…”