PMID- 30505274 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 9 DP - 2018 TI - Bio-Guided Fractionation of Papaya Leaf Juice for Delineating the Components Responsible for the Selective Anti-proliferative Effects on Prostate Cancer Cells. PG - 1319 LID - 10.3389/fphar.2018.01319 [doi] LID - 1319 AB - Alternative therapies against cancer cells with minimal or no effect on healthy tissues are highly sought after. Prostate cancer (PCa) is the second most frequently diagnosed malignancy in males. The Carica papaya L. leaf extract has been traditionally used by Australian aboriginal people for anticancer properties. In this study, medium polar fraction of papaya leaf extract that had shown anti-proliferative activity in PCa cell lines in vitro, in earlier studies, was further fractionated to 28 fractions by semi-preparative HPLC. Nine of these fractions were identified to possess selective anti-proliferative responses on PCa cells in comparison to non-cancerous cells of prostate gland origin. When these nine sub-fractions were mixed in various combinations, a combination containing six of the specific fractions (FC-3) showed the best potency. FC3 inhibited the growth of BPH-1, PC-3, and LNCaP cells in a concentration-dependent manner with an IC(50) value <20 mug/mL, while (unlike paclitaxel, the positive control) minimal effect was observed on the proliferation of non-cancerous, WPMY-1 and RWPE-1cells. Furthermore, synergistic interaction of FC-3 with paclitaxel was observed with combination index values in the range of 0.89-0.98 and 0.85-1.10 on PC-3 and LNCaP cells, respectively. Untargeted qualitative analysis using UHPLC (Ultra High-Performance Liquid Chromatography)-QToF (Quadrupole Time of-Flight) mass spectrometry and screening against the METLIN database indicated presence of multiple known anticancer compounds in the FC-3 extract. These outcomes show that the potent and selective anti-proliferative effects are due to a range of bio-active compounds within the medium polar fraction of papaya leaf juice. FAU - Pandey, Saurabh AU - Pandey S AD - School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia. AD - School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. AD - Australian Prostate Cancer Research Centre, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia. FAU - Walpole, Carina AU - Walpole C AD - School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. AD - Australian Prostate Cancer Research Centre, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia. FAU - Shaw, Paul N AU - Shaw PN AD - School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia. FAU - Cabot, Peter J AU - Cabot PJ AD - School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia. FAU - Hewavitharana, Amitha K AU - Hewavitharana AK AD - School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia. FAU - Batra, Jyotsna AU - Batra J AD - School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. AD - Australian Prostate Cancer Research Centre, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia. LA - eng PT - Journal Article DEP - 20181116 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC6250729 OTO - NOTNLM OT - CyQUANT assay OT - anti-proliferative OT - bioassay guided fractionation OT - papaya OT - prostate cancer EDAT- 2018/12/07 06:00 MHDA- 2018/12/07 06:01 PMCR- 2018/11/16 CRDT- 2018/12/04 06:00 PHST- 2018/06/12 00:00 [received] PHST- 2018/10/29 00:00 [accepted] PHST- 2018/12/04 06:00 [entrez] PHST- 2018/12/07 06:00 [pubmed] PHST- 2018/12/07 06:01 [medline] PHST- 2018/11/16 00:00 [pmc-release] AID - 10.3389/fphar.2018.01319 [doi] PST - epublish SO - Front Pharmacol. 2018 Nov 16;9:1319. doi: 10.3389/fphar.2018.01319. eCollection 2018.