Abstract
Isorhapontigenin (ISO), a tetrahydroxylated stilbenoid, is an analog of resveratrol (Rsv). The various biological activities of Rsv and its derivatives have been previously reported in the context of both cancer and inflammation. However, the anti-cancer effect of ISO against breast cancer has not been well established, despite being an orally bioavailable dietary polyphenol. In this study, we determine the anti-cancer effects of ISO against breast cancer using MCF7, T47D, and MDA-MB-231 cell lines. We observed that ISO induces breast cancer cell death, cell cycle arrest, oxidative stress, and the inhibition of cell proliferation. Additionally, sphingosine kinase inhibition by ISO controlled tubulin polymerization and cancer cell growth by regulating MAPK/PI3K-mediated cell cycle arrest in MCF7 cells. Interestingly, SPHK1/2 gene silencing increased oxidative stress, cell death, and tubulin destabilization in MCF7 cells. This suggests that the anti-cancer effect of ISO can be regulated by SPHK/tubulin destabilization pathways. Overall, ISO successfully induced breast cancer cell death and cell growth arrest, suggesting this phytochemical is a better alternative for breast cancer treatment. Further studies in animal models could confirm the potency and usability of ISO over Rsv for targeting breast cancer, potentially posing an alternative candidate for improved therapy in the near future.
Highlights
Breast cancer is one of the most frequently diagnosed cancers among women worldwide [1].Almost 15–20% of total breast cancers are covered by triple-negative breast cancer (TNBC), while the remaining are of non-TNBC [2]
In spite of being breast cancer cells, TNBCs and non-TNBCs have different we evaluated the role of ISO in controlling the MDA-MB-231 cell migration, and this experiment was characteristics of cell growth
ISO treatment showed a higher potency for inducing MCF7, T47D, and MDA-MB-231 cell death and growth arrest through activation of caspase-dependent cell death cascades
Summary
Breast cancer is one of the most frequently diagnosed cancers among women worldwide [1]. Almost 15–20% of total breast cancers are covered by triple-negative breast cancer (TNBC), while the remaining are of non-TNBC [2]. Non-white women are mostly affected by TNBC, whereas non-TNBC affects all women irrespective of race [3]. Drug resistance and cancer recurrence are the major unsolved problems concerning breast cancer therapy. The severe side effects of chemotherapy and delayed drug resistance further complicate the cancer treatment procedure [4]. Phytochemicals are the most desirable chemopreventive agents because of their greater safety profile
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