Abstract

BackgroundCurrent therapeutic approaches to treat metastatic breast cancer, although effective, have shown many inadvertent side effects such as genotoxicity due to a lack of selectivity. Thus, these treatment plans are not suitable for long-term usage. Natural health product extracts are safe for long-term consumption and some have shown to be medicinally active containing multiple bioactive compounds able target multiple vulnerabilities in cancer. One of which, Hibiscus rosa-sinesis (hibiscus) extract, has been reported to have many medicinal and anticancer properties due to its antioxidant and hypolipidemic effects. However, its efficacy against breast cancer has not been fully investigated and characterized. If effective against cancer, hibiscus extract could potentially be combined with chemotherapeutic treatments in adjuvant therapy to reduce chemotherapy-inducing side effects.MethodWe have investigated aqueous hibiscus flower extract anticancer efficacy, selectivity, and interactions with chemotherapeutics taxol, cisplatin, and tamoxifen in estrogen-receptor positive breast cancer cells, triple-negative human breast cancer cells, and normal non-cancerous cells. Apoptotic morphology and biochemical marker expression were assessed to determine the extent anticancer efficacy of hibiscus. Mitochondrial membrane potential reduction and reactive oxygen species generation were quantified using fluorogenic dyes to determine the mechanism of hibiscus extract action.ResultsHibiscus extract was able to selectively induce apoptosis in both triple-negative and estrogen-receptor positive breast cancer cells in a dosage-dependent manner. Most importantly, addition of hibiscus extract was found to enhance the induction of apoptosis of chemotherapy treatments (taxol and cisplatin) in triple-negative breast cancer cells when compared to treatment alone. Moreover, hibiscus extract addition to chemotherapy treatment was able to increase oxidative stress and decrease mitochondrial membrane potential compared to individual treatments.ConclusionHibiscus extract is effective on breast cancer, most notably on generally resistant triple-negative breast cancer, while being selective for normal healthy cells. Hibiscus extract could supplement chemotherapeutic regimens as an adjuvant and lead to a more efficacious treatment approach to reduce chemotherapy dosages and related toxicity.

Highlights

  • Current therapeutic approaches to treat metastatic breast cancer, effective, have shown many inadvertent side effects such as genotoxicity due to a lack of selectivity

  • Hibiscus extract induces apoptosis in a dosage dependent manner in triple-negative and estrogen-receptor positive breast cancer cells Hot water extract of hibiscus flower was prepared as described in the material and methods

  • To assess the ability of hibiscus extract (HE) to induce apoptosis in breast cancer, triple-negative and ER+ breast cancer cells were fluorescently stained with apoptosis markers Annexin V (AV) and propidium iodide (PI)

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Summary

Introduction

Current therapeutic approaches to treat metastatic breast cancer, effective, have shown many inadvertent side effects such as genotoxicity due to a lack of selectivity. These treatment plans are not suitable for long-term usage. Breast cancer treatment approaches become more complicated once the disease progresses to the complex metastatic stage. An understanding of cell death, in relation to cancer, allows for an assessment of the pathogenesis and treatment of the disease [8]. The exploitation of cellular vulnerabilities in cancerous cells, including oxidative stress and mitochondrial membrane destabilization, by therapeutic agents could trigger apoptosis and potentially eradicate the disease [9, 10]. Many treatments are nonspecific for cancer and can target healthy non-cancerous cells eventually leading to inadvertent side effects and toxicity [11, 12]

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