Investigation of the kunyit asam herbal drink potential as an alternative treatment for cisplatin resistance non-small cell lung cancer (NSCLC)

Abstract

Non-small cell lung cancer (NSCLC), accounting for more than 85% of lung cancer diagnoses, has remained the leading cause of cancer-related death. Chemotherapy has been used as the gold standard treatment to treat it, and one of the common drugs is cisplatin. However, cisplatin can lead to resistance, resulting from a complex interaction of molecular pathways that reduces the efficacy of cisplatin-based therapies, including the upregulated B-cell lymphoma 2 (BCL-2) gene. Cisplatin-resistant NSCLC cells may have cross-resistance to other platinum-based medicines and chemotherapeutic treatments that use similar pathways. This cross-resistance narrows the spectrum of feasible treatment choices, underscoring the need for medicines that target different pathways or processes unaffected by existing resistance mechanisms. Based on the well-documented anti-cancer properties of curcumin and tamarind, the traditional Indonesian kunyit asam herbal drink provides a culturally inherited and easily accessible mode of consumption, making it a promising avenue for incorporating these bioactive compounds into cancer prevention and adjuvant therapy strategies. This study aims to understand the efficacy of kunyit asam herbal drink as an alternative treatment for cisplatin-resistant lung cancer, especially NSCLC. In this study, the result was found by using several methodologies such as total phenolic acid quantification, cell viability assay, and gene expression analysis. According to the findings, cisplatin-resistant cells had much greater viability rates after cisplatin treatment, most likely due to improved DNA repair capacities and changed drug transport routes. Notably, the kunyit asam extract exhibited dose-dependent cytotoxicity in both cell lines, with substantial effects against cisplatin-resistant cells, indicating its potential as an alternative treatment agent for chemoresistance. The extract's capacity to cause cell death via methods different than standard chemotherapies highlights its potential as an adjuvant therapy. Furthermore, quantitative gene expression analysis demonstrated that cisplatin treatment increased BCL-2, an anti-apoptotic protein, more than kunyit asam extract in both cell lines, with the cisplatin-resistant line showing much greater upregulation.