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Using scCO<jats:sub>2<\/jats:sub> as a solvent, six operating parameters were studied and the supercritical fluid extraction (SFE) process investigated using a factorial design 2<jats:sup>6-2<\/jats:sup>. The processing values promoting cytotoxic activity towards SCC-25 are: high pressure (250\u2009bar), low temperature (35\u2009\u00b0C), extended processing time (180\u2009minutes), as well as a large amount of starting material (5\u2009g). The factorial experimental design successfully identified the key parameters controlling the SFE of molecules cytotoxic to SCC cells from <jats:italic>C. papaya<\/jats:italic> juice. This study also validated the extraction method and showed that the SFE yield was reproducible. The chromatographic and mass spectrometric profiles of the scCO<jats:sub>2<\/jats:sub> extract acquired with high-resolution quadrupole time-of-flight mass spectrometry (LC-QToF-MS) were used to tentatively identify the bioactive compounds using comparative analysis. The principal compounds were likely to be mainly vitamins and phytosterols, some of which are documented to be cytotoxic to cancer cells.<\/jats:p>","DOI":"10.1038\/s41598-018-37171-9","type":"journal-article","created":{"date-parts":[[2019,2,8]],"date-time":"2019-02-08T13:55:25Z","timestamp":1549634125000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Factorial design-assisted supercritical carbon-dioxide extraction of cytotoxic active principles from Carica papaya leaf juice"],"prefix":"10.1038","volume":"9","author":[{"given":"Kooi-Yeong","family":"Khaw","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Odile","family":"Parat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul Nicholas","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thao T. 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