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Alginate Oligosaccharide DP5 Exhibits Antitumor Effects in Osteosarcoma Patients following Surgery
Jiayu Chen1, Yu Hu2, Lirong Zhang2
1Department of Basic Medicine, Medical School, Shaoxing UniversityShaoxing, China.
Abstract:
Osteosarcoma is a malignant musculoskeletal tumor that has high-rate morbidity and mortality worldwide. Alginate oligosaccharide (AOS), a natural product, has antitumor activities and may have therapeutic effects in osteosarcoma, the molecular mechanisms of which remain unclear. AOS was prepared from alginate sodium using alginate lyase. The fractions of AOS were further isolated by size-exclusion chromatography and verified by electrospray ionization mass spectrometry (ESI-MS). Osteosarcoma patients were enrolled in the study and assigned into two groups: AOS (AG, oral administration of 10-mg AOS daily) and control groups (CG, placebo). Preoperative and postoperative clinical data were investigated and analyzed. Four different degrees of polymerizations (DPs) were isolated and denominated as DP2, DP3, DP4, and DP5. Among these polymers, only DP5 showed antitumor functions on osteosarcoma cells. Before surgery and the outcome of primary end point after surgery, no significant differences were observed for clinical data and tumor size between the AG and CG groups (P > 0.05). After 2-year therapy, the mean tumor volume was 214.6 ± 145.7 c.c. in AG and 467.2 ± 225.3 c.c in CG (P < 0.01). The rate of local recurrence was 44.9 and 68.7% in AG and CG, respectively (P < 0.01). AOS treatment resulted in the increase in serum levels of SOD, GSH, HDL-C, and reduction in the levels of interleukin-1 (IL-1) beta and IL-6; the ratios of AST/ALT; and triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol LDL-C, and malondialdehyde (MDA) (P < 0.05). AOS reduces osteosarcoma progression, which is associated with improvement in antioxidant and anti-inflammatory capacities of patients, and may be used as a potential drug for osteosarcoma therapy.
Insights
Alginate oligosaccharide (AOS) shows potential in treating osteosarcoma by reducing tumor volume and recurrence. This natural compound improves antioxidant and anti-inflammatory markers in patients, suggesting a new therapeutic avenue.
Area of Science:
- Biochemistry
- Oncology
- Pharmacology
Background:
- Osteosarcoma is a prevalent and aggressive musculoskeletal malignancy with high mortality rates.
- The therapeutic potential of alginate oligosaccharide (AOS), a natural product, for osteosarcoma is suggested but its mechanisms are not fully understood.
Purpose of the Study:
- To investigate the therapeutic effects and underlying mechanisms of alginate oligosaccharide (AOS) in osteosarcoma patients.
- To evaluate the efficacy of different fractions of AOS, specifically varying degrees of polymerization (DPs), in managing osteosarcoma.
Main Methods:
- Alginate oligosaccharide (AOS) was prepared and fractionated by size-exclusion chromatography, with DP5 identified as the active fraction.
- Osteosarcoma patients were enrolled in a randomized controlled trial, receiving either 10-mg oral AOS daily or a placebo for two years.
- Clinical data, tumor volume, local recurrence rates, and serum biochemical markers (antioxidant, inflammatory, lipid profiles) were analyzed.
Main Results:
- Only the DP5 fraction of AOS demonstrated antitumor activity against osteosarcoma cells.
- After two years, the AOS group showed significantly reduced mean tumor volume (214.6 c.c. vs. 467.2 c.c.) and local recurrence rates (44.9% vs. 68.7%) compared to the control group.
- AOS treatment led to improved antioxidant status (increased SOD, GSH), enhanced lipid profiles (increased HDL-C), and reduced inflammation (decreased IL-1β, IL-6, MDA).
Conclusions:
- Alginate oligosaccharide (AOS), particularly the DP5 fraction, effectively reduces osteosarcoma progression and recurrence.
- The therapeutic benefits of AOS are associated with enhanced antioxidant and anti-inflammatory capacities in patients.
- AOS represents a promising natural compound for potential use in osteosarcoma therapy.
