4.3. Phytomedicines targeting Hedgehog signaling pathway
Leaf extract of Withania somnifera was found to contain
withaferin A, which targets hedgehog pathway by inhibiting GLI1–DNA
complex (Yoneyama et al., 2015) . Treatment of breast CSCs with
curcumin was reported to downregulate Shh pathway (D. Wang et
al., 2017) . Similarly, sulforaphane showed promising results for
elimination of pancreatic CSCs by suppression of Sonic hedgehog–GLI
pathway (S.-H. Li et al., 2013) . BRM270, significantly
suppressed Shh/Gli1 signaling pathway, contributing to EMT gene
downregulation, and thus prevented metastasis of CD44+ pancreatic ductal
adenocarcinoma cells (PDAC) cells. In vivo study established that
tumor growth derived from CD44+ PDAC was suppressed by 5 mg/kg dose of
BRM270 (Huynh et al., 2019) . Baicalein, an active compound in
the formulation of Qingyihuaji, was evidently described to repress the
self-renewal of pancreatic CSCs by inhibiting the signaling pathway of
Sonic Hedgehog (Song et al., 2018) . Honokiol, obtained from
Magnolia plant also inhibited Shh, thus suppressed the growth of
pancreatic cancer with 150 mg/kg dose in mouse xenograft model(Averett et al., 2016) .
A study established that, MSC500, a Korean herbal preparation consisting
primarily of 8 herbs including Phellinus linteus, Gastrodiaelata ,
and Mulberry leaf modulated all three signaling pathways (Notch,
Wnt, and Hedgehog) in glioblastoma cells (Yao et al., 2014) . It
has been observed that treatment of CSCs with phytomedicines improves
their sensitization to conventional chemotherapy drugs. Ovatodiolide was
shown to augment the chemotherapeutic effect of temozolomide for
glioblastoma cells (Su et al., 2019) . Furthermore, it enhanced
the cisplatin treatment for nasopharyngeal (S.-C. Liu et al.,
2019) and oral CSCs (Lin et al., 2018) . Similarly,
sulforaphane, found in cruciferous vegetables enhanced cisplatin
treatment for nasopharyngeal carcinoma (Chen et al., 2019) .
Curcumin improved the sensitivity of paclitaxel, cisplatin, doxorubicin,
and mitomycin C for breast CSCs (Zhou et al., 2015) . Studies
have shown that ginsenoside-Rb1 improved cisplatin and