Anthocyanidins Inhibit Growth and Chemosensitize Triple-Negative Breast Cancer via the NF-κB Signaling Pathway.
Farrukh AqilRadha MunagalaAshish Kumar AgarwalJeyaprakash JeyabalanNeha TyagiShesh Nath RaiRamesh C GuptaPublished in: Cancers (2021)
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Due to the lack of drug-targetable receptors, chemotherapy is the only systemic treatment option. Although chemotherapeutic drugs respond initially in TNBC, many patients relapse and have a poor prognosis. Poor survival after metastatic relapse is largely attributed to the development of resistance to chemotherapeutic drugs. In this study, we show that bilberry-derived anthocyanidins (Anthos) can inhibit the growth and metastasis of TNBC and chemosensitize paclitaxel (PAC)-resistant TNBC cells by modulating the NF-κB signaling pathway, as well as metastatic and angiogenic mediators. Anthos administered orally significantly decreased MDA-MB-231 orthoxenograft tumor volume and led to lower rates of lymph node and lung metastasis, compared to control. Treatment of PAC-resistant MDA-MB-231Tx cells with Anthos and PAC in combination lowered the IC 50 of PAC by nearly 20-fold. The combination treatment also significantly ( p < 0.01) decreased the tumor volume in MDA-MB-231Tx orthoxenografts, compared to control. In contrast, Anthos and PAC alone were ineffective against MDA-MB-231Tx tumors. Our approach of using Anthos to inhibit the growth and metastasis of breast cancers, as well as to chemosensitize PAC-resistant TNBC, provides a highly promising and effective strategy for the management of TNBC.
Keyphrases
- signaling pathway
- cell cycle arrest
- induced apoptosis
- pi k akt
- poor prognosis
- lymph node
- breast cancer cells
- squamous cell carcinoma
- long non coding rna
- epithelial mesenchymal transition
- computed tomography
- lps induced
- chronic kidney disease
- magnetic resonance
- combination therapy
- toll like receptor
- endoplasmic reticulum stress
- patient reported outcomes
- inflammatory response
- free survival
- contrast enhanced
- childhood cancer