Oridonin enhances antitumor effects of doxorubicin in human osteosarcoma cells

Abstract

Background Doxorubicin is the chemotherapeutic drug of choice in osteosarcoma treatment, but its cumulative administration causes dilated cardiomyopathy. Combination therapy represents a potential strategy to reduce the therapeutic dosage of the chemotherapeutic agent and minimize its side effects. The aim of this study was to evaluate the potential of oridonin, a natural product from the medicinal herb Rabdosia rubescens, to act in combination with doxorubicin for osteosarcoma treatment. To date, there are no reports of the simultaneous administration of both drugs in osteosarcoma therapy. Methods The combined administration of different doses of oridonin and doxorubicin, as compared with the drugs alone, were tested in an in vitro model of osteosarcoma. The synergistic effect of the drugs on cell death was assessed by alamarBlue™ and by CompuSyn software. Early and late apoptosis markers (JC-1 fluorescence and Annexin V immunofluorescence), as well as the production of reactive oxygen species, were evaluated by flow cytometry. Western blot was used to assess the expression of anti-apoptotic proteins. Results Oridonin and doxorubicin presented a synergistic cytotoxic effect in osteosarcoma cells. In the presence of sub-cytotoxic concentrations of the natural product, there was an increased accumulation of intracellular doxorubicin, increased levels of reactive oxygen species (ROS), alteration of mitochondria membrane potential and a higher rate of apoptosis. Conclusion The combined use of oridonin and doxorubicin could help to reduce the clinical dosage of doxorubicin and its dangerous side effects.

Nano-drug co-delivery system of natural active ingredients and chemotherapy drugs for cancer treatment: a review

“…Oridonin and DOX presented a synergistic cytotoxic effect in osteosarcoma cells. Oridonin increased the accumulation of intracellular DOX and the rate of apoptosis (Kazantseva et al., 2022 ). Compared with brusatol (BR) or CDDP alone, CDDP and BR could exert synergistic anti-tumor effect by increasing the release of cytochrome c in CT-26 cells, decreasing the expression of caspase-3 and caspase-9, and increasing the ratio of the B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 (Chen et al., 2018 ).…”

Anti-Invasive and Anti-Migratory Effects of Ononin on Human Osteosarcoma Cells by Limiting the MMP2/9 and EGFR-Erk1/2 Pathway

“…DOX is an anthracycline presently permitted to treat numerous neoplastic disorders, such as breast and gynecologic cancers, lymphoma, and lung cancer [29]. Additionally, DOX-based chemotherapy has been recognized as the standard treatment for osteosarcoma [30].…”

Traditional Medicinal Plants as a Source of Inspiration for Osteosarcoma Therapy

“…For this reason, to increase the efficiency of osteosarcoma treatment, researchers rely on combination therapy. Recently, a synergistic cytotoxic effect has been described for oridonin and doxorubicin in an in vitro model of osteosarcoma [ 39 ]. Wang et al [ 28 ] investigated the possibility of combining the natural product with Nutlin–3, an inhibitor of mouse double minute 2 (Mdm2) protein, a negative regulator of p53 function.…”