TABLE 4.
Cytotoxic activity of physalins.
| Reference | Physalins | Cell lines | Main results |
|---|---|---|---|
| Fang et al. (2003) | B, F, and H | BC1; Lu1; Col2; KB; LNCap; SW626; SKNSH and M109 | Physalins, especially physalin B, showed broad cytotoxic activity in most of cell lines tested. |
| Lee and Houghton (2005) | B and F | COR L23; MCF-7 | Both physalins displayed cytotoxic activity against cancer cell lines (IC50 values below to 2 µM), being physalin F more active |
| Magalhães et al. (2010) | B and D | CEM; HL-60; K562; HCT-8; MCF-7; MDA-MB-435; MDA-MB-231; PC-3 and B16 | Both compounds displayed considerable cytotoxicity against several cancer cell lines, showing IC50 values ranging from 0.58 to 15.18 µg/ml for physalin B, and 0.28–2.43 µg/ml for physalin D. In addition, antitumour activity in mice transplanted with Sarcoma 180 tumour was confirmed |
| Damu et al. (2007) | B, D, F, J, U, and W | DU-145; 1A9; HCT116; LNCAP; KB; A431; A549; HCT-8; PC-3 and ZR751 | Physalins, especially physalin F (EC50 values in the range of 0.3–1.3 µg/ml), showed broad cytotoxic activity in most of the cell lines tested |
| Ausseil et al. (2007) | B and C | DLD-1 | Both physalins inhibit ubiquitin-proteasome pathway with EC50 values of 3.8 µM for physalin B and 4.4 µM for physalin C |
| Hosoya et al. (2008) | B and F | PANC1 | Both physalins inhibit Headhog/GLI-mediated transcription and presented IC50 values of 2.6 and 5.3 µM against PANC1 cells |
| Vandenberghe et al. (2008) | B | DLD-1 | Physalin B decreased the viability of DLD-1 cells by inhibiting the ubiquitin/proteasome pathway associated with the inhibition of NF-κB induced by TNF and with the induction of the Noxa protein, leading to death by apoptosis |
| Han et al. (2011) | A and B | CWR22Rv1 and C4B2B | Both physalins inhibit the proliferation of C42B and CWR22Rv1 cells by inducing apoptosis from the activation of the MAP kinase, ERK 1/2 and JNK pathways. In addition, both molecules reduced androgen receptor and prostate-specific antigen expression |
| Hsu et al. (2012) | B | A375 and A2058 | Physalin B exhibits cytotoxicity in melanoma cancer cell lines by inducing apoptosis via the NOXA, caspase-3, and mitochondria-mediated pathways |
| Wu et al. (2012) | F | A498; ACHN and UO-31 | Physalin F inhibited cell viability in human renal cancer cells by inducing cell apoptosis through the ROS-mediated mitochondrial pathway and suppressed NF-κB activation |
| He et al. (2013a) | A | A375-S2; HT1080; HepG2; HeLa; A549; U937; HCT116; A431; MCF-7 and HL-60 | Physalin A showed broad cytotoxic activities towards most of the cell lines tested. In HT1080 cells, induced apoptosis associated with caspase-3 and caspase-8 activation and also induced autophagy |
| He et al. (2013b) | A | A375-S2 | Physalin A induced apoptotic cell death via p53-Noxa-mediated ROS generation, and autophagy played a protective role against apoptosis through up-regulating the p38-NF-κB survival pathway in A375-S2 cells |
| He et al. (2014) | A | A375-S2 | Physalin A induces iNOS expression and NO generation promoting apoptosis and autophagy in A375-S2 cells, however autophagy decreases NO production, reducing the rate of apoptosis and protecting cells from death |
| Ooi et al. (2013) | F | T-47D | Physalin F displayed cytotoxic effect (IC50 = 3.6 µg/ml) on human breast T-47D carcinoma by apoptosis through the activation of caspase-3 and c-myc pathways |
| Arai et al. (2014) | B, F, G, H, K, and isophysalin B | DU-145 and PANC1 | Physalins B, F, H, and isophysalin B showed cytotoxic effect against tumor cells with aberrant Hedgehog signaling. Furthermore, only physalin H acts by inhibiting the Hedgehog pathway by inhibiting the formation of the GLI1-DNA complex |
| Ma et al. (2015) | B | HCT116 | Physalin B displayed cytotoxic effect (IC50 = 1.35 µM) on human colon HCT116 cells through the induction of apoptosis from the inhibition of the ubiquitin/proteasome pathway mediated by the generation of mito-ROS and induction of incomplete autophagy. In addition, physalin B activated the MAP kinase pathway, which regulates autophagic and apoptotic responses |
| Kang et al. (2016) | A | A549 | Physalin A inhibits the proliferation of A549 cells through the generation of ROS mediated by the p38 and ERK pathways that led to the expression of p53, p21, and cdc2 proteins and caused cell cycle arrest in the G2/M phase |
| Yang et al. (2016) | A, B, C, D, F, G, I, J, L, M, N, O, P, Z, isophysalin A, and six new physalins | HL60; SMMC-7721; A-549; MCF-7 and SW-480 | Physalins B, F, and J presented the best profiles, with IC50 values above 5 µM to the cancer cells lines evaluated |
| Zhu et al. (2016) | A | H292; H1975; H358; H460 and A549 | Physalin A showed antiproliferative effect in non-small cell lung cancer by activating apoptosis through inhibition of the JAK/STAT3 signaling pathway. In addition, physalin A significantly suppressed tumor xenograft growth |
| Sun et al. (2017a) | Physalins V, VI, VII, VIII, and IX | C4-2B; 22Rv1; 786-O; A-498; ACHN and A375-S2 | Physalin B and F showed antiproliferative activities against all tested human cancer cells with IC50 values of 0.24–3.17 μM |
| Wang et al. (2018) | B | MCF-7; MDA-MB-231 and T-47D | Physalin B reduced the viability of MCF-7 cells by inducing wild-type p53 expression and inhibiting the Akt pathway. In addition, act in MDA-MB-231 and T47D cells by inactivating mutant p53, resulting in the induction of the arrest of the cell cycle in the G2/M phase and promoting the cleavage of PARP and caspases-3, -7, and -9 to initiate death by apoptosis |
| Chen et al. (2018) | F | SW480 and DLD-1 | Physalin F inhibited the growth of SW40 and DLD-1 cells by inhibiting the Wnt glycoprotein and therefore promoted YAP-dependent β-catenin degradation. In addition, physalin F inhibited tumour growth by down-regulating β-catenin in tumour bearing mice |
| Boonsombat et al. (2020) | B, D, F, G, U, and XI | HL-60; MOLT-3; A549; HeLa; HuCCA-1; HepG2 and MDA-MB-231; T4D-7 and S102 | Physalin B and F showed antiproliferative activities against all tested human cancer cells, with IC50 values of 0.38–29.71 μM |
| Cao et al. (2019) | B | A549 | Physalin B downregulates the cyclin B1/CDK complex and causes cell cycle arrest in G2/M. It reduces mitochondrial ATP production, increases levels of reactive oxygen species, and elevates mitochondrial membrane potential, thereby inducing apoptosis of A549 cells |
| Shin et al. (2019) | A | Hepa-1c1c7 and HepG2 | Physalin A reduces the cell viability of liver cancer cells by inducing Nrf2 expression via ERK and p38 pathways |
| Sun et al. (2021) | 7b-ethoxyl-isophysalin C and 3b-ethoxyl-2,3-dihydro-4,7-didehydrophysalin B | PC-3 | 7b-ethoxyl-isophysalin C showed apparent moderate with IC50 values of 8.26 µM, whereas the other physalin exhibited no cytotoxicity against PC-3 cancer cell line |
| Fang et al. (2021) | B | HGC-27 and SGC-7901 | Physalin B inhibited proliferation via cyclin-dependent kinase and induces caspase-dependent apoptosis in HGC-27 cells |
| Ko et al. (2021) | A | MDA-MB-231; MDA-MB-453; HCC-1937 and MCF-7 | Physalin A inhibited proliferation and migration of breast cancer cells and mammospheres formation. In addition, physalin A inhibited the formation of breast cancer stem cells and decreased the transcript levels of BCSC-related genes (Oct4, CD44, Sox2, c-myc, and Nanog) via regulation of the Hedgehog/Hippo signaling pathway |
| Xu et al. (2021) | B, D, F, H, I, J, 5β, 6β-epoxyphysalin C, and 5α-chloro-6β-hydroxyphysalin C | PC-3; MCF-7; NCI-H460 and SF-268 | Physalins F, H, 5β, 6β-epoxyphysalin C, and 5α-chloro-6β-hydroxyphysalin C presented selective cytotoxicity for at least one of the tested cancer cell lines |
| Yang et al. (2021) | B, D, and F | HT1080 | Physalin F, through inhibition of isocitrate dehydrogenase enzyme, showed antiproliferative activity in HT1080 cell and induced apoptosis cells death |
AKT, protein kinase B; ATP, adenosine triphosphate; BCSC, breast cancer stem cells; CDC2, cyclin-dependent kinase 1; EC50, effective concentration of 50%; ERK, extracellular signal-regulated kinases; GLI-1, glioma-associated oncogene; IC50, inhibitory concentration of 50%; iNOS, Nitric Oxide Synthases; JNK; c-Jun N-terminal kinase; MAP, microtubule-associated protein; NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells; NO, nitric oxide; NRF2, nuclear factor erythroid 2-related factor 2; PARp, Poly (ADP-ribose) polymerase; ROS, reactive oxygen species; STAT3, Signal transducer and activator of transcription 3; TNF, tumor necrosis factor.