Synergistic Cytotoxicity of Natural Gallic Acid from Vitis vinifera and Tamoxifen in Human Osteosarcoma U2OS

Hermizi Hapidin; Nur Najihah  Sidek; Shaharum  Shamsuddin

doi:10.55230/mabjournal.v55i1.3595

Authors

Hermizi Hapidin
hermizi@usm.my
Biomedicine Programme, School of Health Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia
Nur Najihah Sidek Biomedicine Programme, School of Health Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia
Shaharum Shamsuddin Biomedicine Programme, School of Health Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia

Keywords:

Cytotoxicity, Gallic acid, Osteosarcoma, Synergistic Effect, Tamoxifen

Abstract

Osteosarcoma is a prevalent and aggressive bone malignancy, primarily affecting children and adolescents. While tamoxifen (TAM) is a commonly used chemotherapeutic agent, its application is often limited by adverse side effects. Gallic acid (GA), a naturally occurring polyphenol, has demonstrated promising anticancer properties and may offer a safer alternative or adjunct in cancer therapy. This study investigates the effects of GA alone and in combination with TAM on the viability and morphology of human osteosarcoma (U2OS) cells. An in vitro model was employed using the MTT assay to assess cell viability after 72 hr of treatment. The half maximal inhibitory concentration (IC₅₀) and combination index (CI) were calculated to evaluate cytotoxicity and drug interaction. Three combination ratios of GA:TAM (75:25, 50:50 & 25:75) were tested. GA and TAM alone exhibited IC₅₀values of 8.258 ± 1.047 µg/mL and 1.814 ± 1.205 µg/mL, respectively. The 25:75 combination yielded the lowest IC₅₀ (1.475 ± 1.189 µg/mL) and a CI of 0.637, indicating a synergistic effect. Other combinations showed higher IC₅₀ and CI values, suggesting reduced efficacy. Morphological analysis using phase contrast microscopy revealed apoptotic features such as cell shrinkage and rounding in treated cells, particularly in the 25:75 combination group. In conclusion, GA, especially when combined with TAM at a 25:75 ratio, enhances therapeutic efficacy while potentially reducing toxicity. This combination may represent a promising strategy for improving osteosarcoma treatment outcomes.

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