Globally, peptide-based anticancer therapies have drawn much attention. Marine organisms are a reservoir of anticancer peptides that await discovery. In this study, we aimed to identify cytotoxic oligopeptides from Sarcophyton glaucum. Peptides were purified from among the S. glaucum hydrolysates produced by alcalase, chymotrypsin, papain, and trypsin, guided by a methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay on the human cervical cancer (HeLa) cell line for cytotoxicity evaluation. Purification techniques adopted were membrane ultrafiltration, gel filtration chromatography, solid phase extraction (SPE), and reversed-phase high-performance liquid chromatography (RP-HPLC). Purified peptides were identified by de novo peptide sequencing. From papain hydrolysate, three peptide sequences were identified: AGAPGG, AERQ, and RDTQ (428.45, 502.53, and 518.53 Da, respectively). Peptides synthesized from these sequences exhibited cytotoxicity on HeLa cells with median effect concentration (EC₅₀) values of 8.6, 4.9, and 5.6 mmol/L, respectively, up to 5.8-fold stronger than the anticancer drug 5-fluorouracil. When tested at their respective EC₅₀, AGAPGG, AERQ, and RDTQ showed only 16%, 25%, and 11% cytotoxicity to non-cancerous Hek293 cells, respectively. In conclusion, AERQ, AGAPGG, and RDTQ are promising candidates for future development as peptide-based anticancer drugs.
Amino Acid Sequence ; Animals ; Anthozoa/chemistry* ; Antineoplastic Agents/pharmacology* ; Chromatography, Gel ; Chromatography, High Pressure Liquid ; Chromatography, Reverse-Phase ; Cytotoxins/pharmacology* ; Drug Discovery ; HEK293 Cells ; HeLa Cells ; Humans ; Hydrolysis ; Marine Toxins/pharmacology* ; Oligopeptides/pharmacology* ; Solid Phase Extraction ; Tandem Mass Spectrometry

Using prostate-specific antigen (PSA) for prostate cancer (PCa) screening led to overinvestigation and overdiagnosis of indolent PCa. We aimed to investigate the value of prostate health index (PHI) and magnetic resonance imaging (MRI) prostate in an Asian PCa screening program. Men aged 50-75 years were prospectively recruited from a community-based PSA screening program. Men with PSA 4.0-10.0 ng ml -1 had PHI result analyzed. MRI prostate was offered to men with PSA 4.0-50.0 ng ml -1 . A systematic prostate biopsy was offered to men with PSA 4.0-9.9 ng ml -1 and PHI ≥35, or PSA 10.0-50.0 ng ml -1 . Additional targeted prostate biopsy was offered if they had PI-RADS score ≥3. Clinically significant PCa (csPCa) was defined as the International Society of Urological Pathology (ISUP) grade group (GG) ≥2 or ISUP GG 1 with involvement of ≥30% of total systematic cores. In total, 12.8% (196/1536) men had PSA ≥4.0 ng ml -1 . Among 194 men with PSA 4.0-50.0 ng ml -1 , 187 (96.4%) received MRI prostate. Among them, 28.3% (53/187) had PI-RADS ≥3 lesions. Moreover, 7.0% (107/1536) men were indicated for biopsy and 94.4% (101/107) men received biopsy. Among the men received biopsy, PCa, ISUP GG ≥2 PCa, and csPCa was diagnosed in 42 (41.6%), 24 (23.8%), and 34 (33.7%) men, respectively. Compared with PSA/PHI pathway in men with PSA 4.0-50.0 ng ml -1 , additional MRI increased diagnoses of PCa, ISUP GG ≥2 PCa, and csPCa by 21.2% (from 33 to 40), 22.2% (from 18 to 22), and 18.5% (from 27 to 32), respectively. The benefit of additional MRI was only observed in PSA 4.0-10.0 ng ml -1 , and the number of MRI needed to diagnose one additional ISUP GG ≥2 PCa was 20 in PHI ≥35 and 94 in PHI <35. Among them, 45.4% (89/196) men with PSA ≥4.0 ng ml -1 avoided unnecessary biopsy with the use of PHI and MRI. A screening algorithm with PSA, PHI, and MRI could effectively diagnose csPCa while reducing unnecessary biopsies. The benefit of MRI prostate was mainly observed in PSA 4.0-9.9 ng ml -1 and PHI ≥35 group. PHI was an important risk stratification step for PCa screening.
Humans ; Male ; Early Detection of Cancer/methods* ; East Asian People ; Image-Guided Biopsy/methods* ; Magnetic Resonance Imaging/methods* ; Prostate/pathology* ; Prostate-Specific Antigen ; Prostatic Neoplasms/pathology* ; Retrospective Studies ; Middle Aged ; Aged