Table 3.
Anticancer activities of alkaloids, saponins, steroids, lignan, and phytoalexin related to inhibition of the JAK/STAT signaling pathway.
| Phytochemical Class | Phytochemical Name | Sources | Anticancer Effect | Mechanism of Action | EC50/IC50 | References |
|---|---|---|---|---|---|---|
| Alkaloids | Capsaicin | Capsicum frutescens L. | Induction of cytotoxicity in human multiple myeloma (U266 and MM.1S) cells | ┴ Constitutive and IL-6-induced activation of STAT3; ┴ JAK1 and c-Src activation | 50 and 50 µM | Bhutani et al., 2007 [139] |
| Evodiamine | Tetradium ruticarpum (A. Juss.) T. G. Hartley | Inhibited proliferation, and induced apoptosis; Cell cycle arrest at G2/M phase in murine Lewis lung (LLC), hepatocellular (HepG2), leukemia (K562), gastric (SGC-7901), colon (COLO-205) cancer cells. |
↓ Constitutive and IL-6-induced activation of STAT3 tyrosine 705 (Tyr705); ↓ JAK2, Src and ERK1/2; ┴ STAT3–DNA binding activity |
113, 8.516, 5, 10, 27.15 µM | Yang et al., 2013 [81] | |
| Indirubin | Angelica sinensis (Oliv.) Diels | Reduced cell viability in human prostate and breast cancer cells; induced apoptosis; Cell cycle arrest at G1/S or G2/M |
┴ STAT3 signaling; ┴ STAT3 phosphorylation |
~4 µM for each cell line | Chen et al., 2018 [234] | |
| Saponins | β-Escin | Aesculus hippocastanum L. | Induction of cytotoxicity in human hepatocellular carcinoma (HepG2, PLC/PRF5, and HUH-7) cells | ┴ Activation of STAT3 and induced expression of SHP-1; ┴ Phosphorylation of JAK1, JAK2, and c-Src |
Not specified | Tan et al., 2010 [238] |
| Steroid | Diosgenin | Trigonella foenum-graecum L. | Induced cytotoxicity in human hepatocellular carcinoma (C3A, HUH-7, and HepG2) cells | ┴ Constitutive and inducible activation of STAT3 | 100, 100 and 50 µM | Li et al., 2010 [244] |
| Ergosterol peroxide | Agaricus bisporus | Induced cytotoxicity in human multiple myeloma (U266) cells | ┴ Phosphorylation of JAK2; ┴ phosphorylation; ┴ DNA binding activity; ┴ Nuclear translocation of STAT3 |
Not specified | Rhee et al., 2012 [80] | |
| Guggulsterone | Commiphora mukul (Hook. ex Stocks) Engl. | Induced cytotoxicity in human multiple myeloma (U266) cells | ┴ Constitutive andIL-6-induced STAT3; ┴ Phosphorylation of JAK2 and Src |
25 µM | Ahn et al., 2008 [250] | |
| Lignan | Arctiin | Centaurea imperialis Hausskn. ex Bornm., Arctium lappa L., Forsythia viridissima Lindl., Himalaiella heteromalla (D. Don) Raab-Straube., and Trachelospermumas iaticum (Siebold & Zucc.) Nakai | Inhibited proliferation, cell cycle arrest at G2/M stage in human multiple myeloma cells |
┴ STAT3 phosphorylation in tyrosine 705; ┴ Constitutive enactment of Src phosphorylation and JAKs 1/2; ↑ mRNA, ↑ protein levels of protein tyrosine phosphatase ε; ┴ STAT3 regulated gene products |
Not specified | Lee et al., 2019b [254] |
| Phytoalexin | Brassinin | Brassica rapa L. | Induced apoptosis in lung cancer cells (A549) in an in vivo mouse model | ┴ STAT3 activation; ┴ Both constitutive and IL-6-inducible STAT3 activation; ┴ Phospho-STAT3, ┴ Ki-67 and ┴ CD31 |
Not specified | Lee et al., 2015 [257] |
Various symbols (↑, ↓ and ┴) indicate increase, decrease and inhibition in the obtained variables, respectively.