Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, having a poor prognosis and rapid metastases. TNBC is characterized by the absence of estrogen, progesterone, and human epidermal growth receptor-2 (HER2) expressions and has a five-year survival rate. Compared to other breast cancer subtypes, TNBC patients only respond to conventional chemotherapies, and even then, with limited success. Shortages of chemotherapeutic medication can lead to resistance, pressured index therapy, non-selectivity, and severe adverse effects. Finding targeted treatments for TNBC is difficult owing to the various features of cancer. Hence, identifying the most effective molecular targets in TNBC pathogenesis is essential for predicting response to targeted therapies and preventing TNBC cell metastases. Nowadays, natural compounds have gained attention as TNBC treatments, and have offered new strategies for solving drug resistance. Here, we report a systematic review using the database from Pubmed, Science Direct, MDPI, BioScince, Springer, and Nature for articles screening from 2003 to 2022. This review analyzes relevant signaling pathways and the prospect of utilizing natural compounds as a therapeutic agent to improve TNBC treatments in the future.

Background: The combination of herbal extracts has the potential to enhance cytotoxic effects against cancer cells. This study explores the combined cytotoxic effects of Curcuma longa and Phyllanthus niruri extracts on HCT-116 colorectal cancer cells. Objective: To assess the cytotoxic effects of Curcuma longa and Phyllanthus niruri extracts when used in combination and to determine the most effective ratio for inhibiting HCT-116 cell growth. Methods: HCT-116 cells were treated for 24 hours with varying concentrations of Curcuma longa and Phyllanthus niruri extracts based on the IC50 values of each extract administered individually. The concentrations for Phyllanthus niruri were 164 µg/mL (one part), 82 µg/mL (half part), and 41 µg/mL (quarter part), while for Curcuma longa the concentrations were 47 µg/mL (one part), 24 µg/mL (half part), and 12 µg/mL (quarter part). Cytotoxicity was assessed using the MTT assay. Results: The combination of Phyllanthus niruri and Curcuma longa extracts demonstrated varied cytotoxic effects. The most effective combination was identified as Phyllanthus niruri to Curcuma longa ratio of 1:0.25, resulting in a 13.5% cell viability rate. Interaction studies using the Chou-Talalay method indicated that the combination index (CI) revealed the most synergistic effect at a ratio of 0.25:0.50. Conclusion: The study identifies that the combination of Phyllanthus niruri and Curcuma longa extracts exhibits synergistic cytotoxic effects on HCT-116 cells, with the optimal combination showing significant inhibition of cell growth. These findings support further investigation into the synergistic potential of these extracts for colorectal cancer therapy.