Low-dose Andrographolide Synergizes With Cytarabine or Vincristine in Plasma Cell Neoplasm Cell Lines.

BACKGROUND/AIM: Andrographolide (Andro), a diterpene lactone from Andrographis paniculata, induces apoptosis via reactive oxygen species (ROS)-dependent mitochondrial dysfunction but achieves low plasma concentrations because of its lipophilicity. We investigated whether low-dose Andro potentiates the cytotoxicity of the mechanistically distinct agents cytarabine (Ara-C) and vincristine (VCR) in plasma cell neoplasm cell lines.

MATERIALS AND

METHODS

Human plasma cell neoplasm cell lines H929 and ARH77 were treated with Andro alone or in combination with Ara-C or VCR. Cell viability was assessed in dose- and time-response experiments, and pharmacologic interactions were quantified using the combination index (CI) method. Apoptosis was evaluated by Annexin V staining, and cell-cycle distribution was analyzed to examine mechanistic complementarity.

RESULTS

Andro decreased viability in a dose- and time-dependent manner (IC50 at 48 h: 3.4 μM in H929; 7.5 μM in ARH77). Combining Andro with Ara-C or VCR further reduced viability; in H929 cells, all combination conditions yielded CI values <1.0, indicating synergy. Combination treatments markedly increased Annexin V-positive fractions, implicating apoptosis as a major contributor to enhanced cytotoxicity. While Andro alone did not appreciably alter cell-cycle profiles, it modestly influenced Ara-C- and VCR-associated changes in cell-cycle distribution, consistent with complementary mechanisms.

CONCLUSION

Low-dose Andro strengthens Ara-C- and VCR-driven cytotoxic programs and provides a quantitative rationale for Andro-based combination strategies in plasma cell neoplasms and related hematologic malignancies.