article · Informatics in Medicine Unlocked
Doxorubicin is an effective chemotherapy drug, but severe side effects from dose-dependent oxidative stress restrict its clinical use. Extract from the medicinal plant Rumex vesicarius L. has known antioxidant properties and exhibits anticancer potential. Tested against invasive triple-negative breast cancer cells, the plant extract alone suppressed cancer cell growth and significantly enhanced the efficacy of doxorubicin when combined, substantially lowering the required inhibitory concentration. Molecular assessments revealed that combining the plant extract with doxorubicin reduced the expression of survival and invasion genes, specifically mTOR, Bcl-2, and JNK1. At the same time, the combined treatment augmented the expression of the tumour suppressor gene p21. Computational analysis suggested that bioactive compounds in the plant bind and inhibit PAK4, an oncogene that represses p21. These results show that the plant extract potentiates chemotherapy activity in laboratory cell cultures.
Triple-negative breast cancer is aggressive and difficult to treat. While doxorubicin is a primary chemotherapy option, its clinical usefulness is limited by severe, dose-dependent side effects. Identifying plant-derived extracts that boost the drug's cancer-killing ability could eventually help lower necessary doses and minimise toxicity for patients, supporting the search for safer and more effective combination treatments.
This work is early-stage research limited to in vitro cell cultures and computational modelling. If validated by future testing, it could interest oncology pharmaceutical developers seeking botanical adjuvants to boost existing chemotherapy regimens. However, practical application is distant: comprehensive in vivo animal trials are necessary next steps to evaluate safety, dosing, and therapeutic mechanisms before any clinical formulation or product can be considered.
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Doxorubicin (DOX) is a potent chemotherapeutic drug; however, its use is limited because it induces dose-dependent oxidative stress causing severe adverse effects. Rumex Vesicarius L. (RMX) is a plant used in traditional medicine for its multiple therapeutic virtues including antioxidant potential. We aimed to determine the potency of RMX alone and in combination with DOX against the invasive triple-negative breast cancer (TNBC) cell line MDA-MB-231, and to deduce the underlying mechanism of action by in vitro and in silico analyses. We found that the RMX extract alone and in combination with DOX significantly inhibited the cancer cell proliferation with a 50% inhibitory concentration (IC50) of 2.12 and 0.5 μM respectively. Furthermore, combined treatment of RMX and DOX has induced significant reductions in the relative gene expression of the survival/anti-apoptosis and invasion genes mTOR, Bcl-2, and JNK respectively, while the expression of the p21 tumor suppressor gene was increased. In silico analysis of the RMX extract indicated that some of its bioactive compounds exhibit superior affinity to inhibit the oncogene p21-activated kinase 4 (PAK4), which functions as an inhibitor of the p21 gene. In conclusion, this study reveals that the RMX extract enhances the anticancer efficacy of DOX through molecular mechanisms involving downregulation of mTOR, Bcl-2, and JNK1, while augmenting p21 expression in TNBC possibly by targeting PAK4 as indicated through in vitro and in silico analyses. Finally, we recommend RMX and its bioactive compounds for further in vivo studies to confirm their potential in cancer therapy.
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DOI: 10.1016/j.imu.2022.100869
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