Withania somnifera Modulates Radiation-Induced Generation of Lung Cancer Stem Cells via Restraining the Hedgehog...

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Lung cancer stem cells (CSCs) drive tumor growth, recurrence, and resistance to conventional therapies.
• Targeting CSCs and their associated signaling pathways is crucial for effective lung cancer treatment.

Purpose of the Study:

• To evaluate the inhibitory effects of Withania somnifera (WS) ethanol extract combined with ionizing radiation (IR) on lung CSCs.
• To assess the radiosensitizing potential of WS extract in a female rat lung cancer model.

Main Methods:

• In vitro assays using A-549 cell line to assess proliferation, cell death, and sphere formation.
• In vivo study in a female rat lung cancer model treated with WS extract (500 mg/kg/day) and/or 8 Gy IR.
• Analysis of Hedgehog (Hh) signaling pathway, CSC markers (OCT4, SOX2, CD133, ABCG2, NANOG), and EMT markers (α-SMA, SNAIL-1, Vimentin, E-cadherin).

Main Results:

• WS extract plus IR synergistically inhibited proliferation and induced cell death in A-549 cells, suppressing sphere formation.
• The combination treatment suppressed Hh signaling activation, leading to reduced expression of CSC markers and EMT factors in the rat model.
• WS extract demonstrated radiosensitizing effects, inhibiting stemness and EMT associated with lung CSCs.

Conclusions:

• Withania somnifera extract acts as a potent adjuvant to radiotherapy, inhibiting lung CSCs and EMT.
• The findings provide molecular insights into targeting CSCs and suggest WS extract as a promising therapeutic strategy for lung cancer.
• This study highlights the potential of WS extract in overcoming radioresistance and tumor progression in lung cancer.