Abstract

Pediatric solid tumors (PSTs) are life-threatening and can lead to high morbidity and mortality rates in children. Developing novel remedies to treat these tumors, such as glioblastoma multiforme and sarcomas, such as osteosarcoma, and rhabdomyosarcoma, is challenging, despite immense attempts with chemotherapeutic or radiotherapeutic interventions. Soy (Glycine max) and kudzu roots (KR) (Pueraria spp.) are well-known phytoestrogenic botanical sources that contain high amounts of naturally occurring isoflavones. In the present study, we investigated the antioxidant and cytotoxic effects of the extracts of KR and soy molasses (SM) against PSTs. The green extraction of isoflavones from KR and SM was performed using natural deep eutectic solvents. The extracts were subsequently analyzed by high-performance liquid chromatography (HPLC)-diode array detector (DAD) coupled with high-resolution (HR) mass spectrometry (MS), which identified 10 isoflavones in KR extracts and 3 isoflavones in the SM extracts. Antioxidant and cytotoxic activities of KR and SM extracts were assessed against glioblastoma multiforme (A-172), osteosarcoma (HOS), and rhabdomyosarcoma (Rd) cancer cell lines. The KR and SM extracts showed satisfactory cytotoxic effects (IC50) against the cancer cell lines tested, particularly against Rd cancer cell lines, in a dose-dependent manner. Antioxidant activity was found to be significantly (p ≤ 0.05) higher in KR than in SM, which was consistent with the results of the cytotoxic activity observed with KR and SM extracts against glioblastoma and osteosarcoma cells. The total flavonoid content and antioxidant activities of the extracts were remarkably attributed to the isoflavone content in the KR and SM extracts. This study provides experimental evidence that HPLC-ESI-HRMS is a suitable analytical approach to identify isoflavones that exhibit potent antioxidant and anticancer potential against tumor cells, and that KR and SM, containing many isoflavones, can be a potential alternative for health care in the food and pharmaceutical industries.

Highlights

  • Cancer is considered the most crucial disease with rapidly increasing incidence worldwide, among pediatric patients

  • The total flavonoid content and antioxidant activities of the extracts were remarkably attributed to the isoflavone content in the kudzu roots (KR) and soy molasses (SM) extracts

  • Pueraria roots and Glycine max are botanical phytoestrogenic sources well-known for their antioxidant and Phytoestrogens are naturally found in bioactive compounds with diverse biological functions

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Summary

Introduction

Cancer is considered the most crucial disease with rapidly increasing incidence worldwide, among pediatric patients. Cancers affecting pediatric patients, including pediatric solid cancers (PSCs), are highly metastatic, demonstrate an inferior prognosis, and are largely resistant to current therapeutic regimens Brain tumors, such as glioblastoma multiforme (GBM) and sarcomas, such as osteosarcoma (OS) and rhabdomyosarcoma (RMS), comprise approximately 40% of the pediatric solid tumors (PSTs) [1,2]. Previous studies have acknowledged the use of radiotherapeutic and chemotherapeutic agents for the treatment of these tumors These therapeutic approaches are toxic, ineffective due to resistance of tumor cells, besides being unsafe for human consumption [7,8]. Accumulating evidence has substantially confirmed the fundamental health benefits of the consumption of these isoflavones Owing to their various health-promoting properties, such as cancer prevention, reduction of oxidative stress, and alleviation of osteoporosis, isoflavones are considered potential targets in the pharmaceutical industry, which can be obtained via a nutritious diet [16,17]. Soy molasses (SM) and parts of kudzu, e.g., KR, are regarded as waste in the manufacturing process; they need to be recycled and repurposed [18]

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