Selectivity and In Vitro Safety of Indonesian Nigella sativa Extract as a Supportive Treatment for Cervical Cancer: Evidence from a Locally Cultivated Tropical Bioresource

Abstract

Cervical cancer ranks second among cancers affecting Indonesian women, with 36,633 new cases and 21,003 deaths annually. Cisplatin-based chemoradiation causes nephrotoxicity in 45% of patients, highlighting the need for safe, locally sourced supportive agents. Nigella sativa (black cumin), widely cultivated in Indonesia, offers a sustainable, cost-accessible tropical bioresource for evidence-based phytopharmaceutical development from Indonesia’s biodiversity. This study evaluated the selectivity and in vitro safety of a 96% ethanolic extract of Indonesian Nigella sativa (EE NS) via MTT assay on HeLa cervical cancer and Vero normal kidney cells. GC-MS identified 20 compounds dominated by linoleic acid derivatives (45.88%) and monoterpenes; HPLC confirmed thymoquinone at 0.04%. EE NS produced dose-dependent inhibition in both lines, with HeLa markedly more sensitive than Vero. IC₅₀ values were 1,053 ppm (HeLa) and 3,718 ppm (Vero). The Selectivity Index (SI = 3.53) exceeds the safety threshold (SI > 3), confirming 3.5-fold greater cytotoxicity toward malignant than normal renal cells. Morphological analysis confirmed MTT results: HeLa cells exhibited apoptosis-like changes while Vero cells maintained structural integrity at low-to-moderate concentrations. Indonesian Nigella sativa demonstrates selective cytotoxicity despite low thymoquinone content, suggesting contributions from other identified phytochemicals, supporting its development as a safe phytopharmaceutical from locally cultivated tropical bioresources.