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Rep"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>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 <jats:italic>Rabdosia rubescens<\/jats:italic>, 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The combined administration of different doses of oridonin and doxorubicin, as compared with the drugs alone, were tested in an <jats:italic>in vitro<\/jats:italic> model of osteosarcoma. The synergistic effect of the drugs on cell death was assessed by <jats:italic>alamarBlue<\/jats:italic><jats:sup><jats:italic>\u2122<\/jats:italic><\/jats:sup> and by <jats:italic>CompuSyn<\/jats:italic> 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The combined use of oridonin and doxorubicin could help to reduce the clinical dosage of doxorubicin and its dangerous side effects.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s43440-021-00324-1","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T11:04:34Z","timestamp":1629803074000},"page":"248-256","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Oridonin enhances antitumor effects of doxorubicin in human osteosarcoma cells"],"prefix":"10.1007","volume":"74","author":[{"given":"Liliya","family":"Kazantseva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4849-8931","authenticated-orcid":false,"given":"Jos\u00e9","family":"Becerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6159-6045","authenticated-orcid":false,"given":"Leonor","family":"Santos-Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"issue":"11","key":"324_CR1","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1038\/nrc3838","volume":"14","author":"M Kansara","year":"2014","unstructured":"Kansara M, Teng MW, Smyth MJ, Thomas DM. 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