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.