The Multifaceted Therapeutic Mechanisms of Curcumin in Osteosarcoma: State-of-the-Art

Abstract

Osteosarcoma is a major form of malignant bone tumor that typically occurs in young adults and children. The combination of aggressive surgical strategies and chemotherapy has led to improvements in survival time, although individuals with recurrent or metastatic conditions still have an extremely poor prognosis. This disappointing situation strongly indicates that testing novel, targeted therapeutic agents is imperative to prevent the progression of osteosarcoma and enhance patient survival time. Curcumin, a naturally occurring phenolic compound found in Curcuma longa, has been shown to have a wide variety of anti-tumor, anti-oxidant, and anti-inflammatory activities in many types of cancers including osteosarcoma. Curcumin is a highly pleiotropic molecule that can modulate intracellular signaling pathways to regulate cell proliferation, inflammation, and apoptosis. These signaling pathways include RANK/RANKL, Notch, Wnt/β-catenin, apoptosis, autophagy, JAK/STAT, and HIF-1 pathways. Additionally, curcumin can regulate the expression of various types of microRNAs that are involved in osteosarcoma. Therefore, curcumin may be a potential candidate for the prevention and treatment of osteosarcoma. This comprehensive review not only covers the use of curcumin in the treatment of osteosarcoma and its anti-cancer molecular mechanisms but also reveals the novel delivery strategies and combination therapies with the aim to improve the therapeutic effect of curcumin.

Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets

“…Cao et al [110] experimentally found that cinobufotalin was able to inhibit Notch signaling pathway, decrease the expression of Notch-1, Hes-1, Hes-5 and Hey-1 genes in OS cell lines, inhibit OS cell survival and induce OS cell apoptosis, and then inhibit the growth of transplanted tumors in mice. Similarly, Farnood et al, Zahedipour et al [92,111] applied curcumin to OS cells, and found that this compound could also downregulate Notch-1, Hes-1, Hey-1, and Hey-2 mRNA expression levels, inhibit cyclin D1, MMP-2, and MMP-9 protein expression levels, and regulate tumor cell growth, inflammatory expression, and apoptotic progression by inhibiting the Notch signaling pathway, so as to have the properties of anti-inflammatory, anti-oxidant, and anti-cancer. Niu et al [112] experimentally found that cannabinoids down-regulated the expression of Notch-1, MMP-2 and VEGF through the Win/Notch signaling pathway, which could not only inhibit the generation of tumor collateral vessels, but also inhibit the proliferation, metastasis and invasion of OS cells.…”

“…Hederoside C P. koreana MG-63, U2OS [100] Salidroside Rhodiola rosea L. U2OS, MG-63 [101] Tubocapsenolide A Tubocapsicum anomalum SHP-2 [102] Andrographolide Andrographis paniculata U2OS [103] Pacilitaxel Taxus wallichiana var. chinensis (Pilger) Florin U2OS, MG-63 [104] Resveratrol Veratrum album MNNG/HOS, MG-63 [105] β-caryophyllene Dianthus chinensis L. MG-63 [106] Sodium cantharidate Mylabris phalerata Pallas MG-63 [107] Tanshinone I Salvia miltiorrhiza Bunge U2OS, MOS-J [108,109] Notch pathway Cinobufagin Bufo raddei U2OS, MG-63 [110] Curcumin Curcuma longa L. U2OS [92,111] Cannabinoids Cannabis sativa L. MG-63 [112] Dihydroartemisinin Artemisia caruifolia Buch.-Ham. ex Roxb.…”

Hypoxia inducible factor-1ɑ as a potential therapeutic target for osteosarcoma metastasis

“…For instance, the synthesis of vancomycin derivative T-methyl chloride can stabilize HIF-1α protein and activate its transcriptional activity, thereby inducing gene expression of downstream targets such as VEGF and GLUT-1 ( Magae et al, 2019 ). Moreover, curcumin exerts multiple inhibitory effects on OS metastatic cells including cell adhesion and vascular remodeling ( Zahedipour et al, 2021 ). Therefore, anti-angiogenesis may simultaneously target multiple molecular mechanisms involved in the process of OS metastasis, making it the most promising therapeutic approach for inhibiting OS metastasis.…”

The Use of Hydrogels for the Treatment of Bone Osteosarcoma via Localized Drug-Delivery and Tissue Regeneration: A Narrative Review

“…Yu et al (2021) demonstrated the development of Cur-loaded chitosan nanoparticles encapsulated in a methacrylated silk fibroin/hyaluronic acid (CCNPs-SF/HAMA) hydrogel, which proved to be effective in reducing the viability of osteosarcoma cells and promoting the proliferation of osteoblasts in vitro [ 94 ]. Cur, a natural polyphenol derived from turmeric Curcuma longa, has shown anti-tumor, anti-oxidant, and anti-inflammatory activities against osteosarcoma, as well as increased osteoblast proliferation and bone formation [ 95 , 96 , 97 ]. The CCNPs-SF/HAMA hydrogels loaded with Cur demonstrated that 150 μg/mL of Cur demonstrated simultaneous anti-cancer effects in MG-63 cell cultures, significantly decreasing cell viability from 100% to approximately 56% and osteoblast proliferative effects in MC3T3-E1 cell cultures, significantly increasing the cell viability from 100% to 124.5% ( Figure 4 ) [ 98 ].…”