Abstract
Sulforaphane (SFN), an active compound in cruciferous vegetables, has been characterized by its antiproliferative capacity. We investigated the role and molecular mechanism through which SFN regulates proliferation and self-renewal of lung cancer stem cells. CD133+ cells were isolated with MACs from lung cancer A549 and H460 cells. In this study, we found that SFN inhibited the proliferation of lung cancer cells and self-renewal of lung cancer stem cells simultaneously. Meanwhile, the mRNA and protein expressions of Shh, Smo, Gli1 and PHC3 were highly activated in CD133+ lung cancer cells. Compared with siRNA-control group, Knock-down of Shh inhibited proliferation of CD133+ lung cancer cells, and decreased the protein expression of PHC3 in CD133+ lung cancer cells. Knock-down of PHC3 also affected the proliferation and decreased the Shh expression level in CD133+ lung cancer cells. In addition, SFN inhibited the activities of Shh, Smo, Gli1 and PHC3 in CD133+ lung cancer cells. Furthermore, the inhibitory effect of SFN on the proliferation of siRNA-Shh and siRNA-PHC3 cells was weaker than that on the proliferation of siRNA-control cells. Sonic Hedgehog signaling pathway might undergo a cross-talk with PHC3 in self-renewal of lung cancer stem cells. SFN might be an effective new drug which could inhibit self-renewal of lung cancer stem cells through the modulation of Sonic Hedgehog signaling pathways and PHC3. This study could provide a novel way to improve therapeutic efficacy for lung cancer stem cells.
Highlights
Lung cancer is one of the most prevalent cancers which accounts for approximately one-fourth of the cancer incidence and is the second leading cause of death bothIncreasing evidence of the existence of cancer stem cells (CSCs) in lung cancer explains why standard chemotherapy or radiotherapy regimens against lung cancer are usually ineffective and result in further tumor recurrence and progression (HermannWang et al AMB Expr (2021) 11:121 et al 2010)
SFN inhibits the growth of lung cancer cells and self‐renewal of lung CSCs To explore the role of SFN in lung cancer cells, we first detected cell viability through the MTT assay
To further determine whether the Sonic Hedgehog (SHH) signaling pathways and Polyhomeotic Homolog 3 (PHC3) had an abnormal expression in human lung CSCs, we examined the protein expression level of Sonic hedgehog (Shh), Smo, Gli1 and PHC3 in C D133+ cells and in CD133− cells
Summary
Lung cancer is one of the most prevalent cancers which accounts for approximately one-fourth of the cancer incidence and is the second leading cause of death bothIncreasing evidence of the existence of cancer stem cells (CSCs) in lung cancer explains why standard chemotherapy or radiotherapy regimens against lung cancer are usually ineffective and result in further tumor recurrence and progression (HermannWang et al AMB Expr (2021) 11:121 et al 2010). Increasing evidence of the existence of cancer stem cells (CSCs) in lung cancer explains why standard chemotherapy or radiotherapy regimens against lung cancer are usually ineffective and result in further tumor recurrence and progression It has been reported that C D133+ subpopulation of multipotent cells has the biological features of CSCs which possess extremely proliferative and self-renewal characteristics (Kim and Ryu 2017; Mizugaki et al 2014). CSCs are only a small part of tumors, they have a powerful ability to self-renew and divide. The tumors rich in CSCs are more aggressive and lead to worse clinical outcomes. The development of therapeutic strategies and drugs that target CSCs can eradicate tumors effectively and reduce the risk of recurrence and metastasis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
