| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-1994 | |
| Phytochemical name or plant extracts | Pygenic acid A (PA) | |
| PMID | 33182770 | |
| Literature evidence | Here, by screening for anoikis sensitizer using natural compounds, we found that pygenic acid A (PA), a natural compound from Prunella vulgaris, not only induced apoptosis but also sensitized the metastatic triple-negative breast cancer cell lines, MDA-MB-231 cells (human) and 4T1 cells (mouse), to anoikis. | |
| IUPAC name | (1S,2R,4aS,6aR,6aS,6bR,8aR,10S,11R,12aR,14bS)-10,11-dihydroxy-1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid | |
| Phytochemicals’ class or type of plant extracts | NA | |
| Source of phytochemicals or plant Extracts | Prunella vulgaris | |
| Geographical availability | Afghanistan, Alabama, Alaska, Albania, Alberta, Aleutian Is., Algeria, Altay, Amur, Arizona, Arkansas, Assam, Austria, Azores, Baleares, Baltic States, Belarus, Belgium, British Columbia, Bulgaria, Buryatiya, California, Canary Is., Cape Verde, Central European Rus, China North-Central, China South-Central, China Southeast, Colorado, Connecticut, Corse, Costa Rica, Cyprus, Czechoslovakia, Delaware, Denmark, District of Columbia, Dominican Republic, East Aegean Is., East European Russia, East Himalaya, Finland, Florida, France, Føroyar, Georgia, Germany, Great Britain, Greece, Guatemala, Hainan, Haiti, Hungary, Iceland, Idaho, Illinois, India, Indiana, Inner Mongolia, Iowa, Iran, Iraq, Ireland, Irkutsk, Italy, Jamaica, Japan, Kamchatka, Kansas, Kazakhstan, Kentucky, Khabarovsk, Kirgizstan, Korea, Krasnoyarsk, Kriti, Krym, Kuril Is., Labrador, Lebanon-Syria, Louisiana, Madeira, Maine, Manchuria, Manitoba, Maryland, Massachusetts, Mexico Central, Mexico Gulf, Mexico Northeast, Mexico Northwest, Mexico Southeast, Mexico Southwest, Michigan, Minnesota, Mississippi, Missouri, Mongolia, Montana, Morocco, Nansei-shoto, Nebraska, Nepal, Netherlands, Nevada, New Brunswick, New Hampshire, New Jersey, New Mexico, New York, Newfoundland, North Carolina, North Caucasus, North Dakota, North European Russi, Northwest European R, Norway, Nova Scotia, Ohio, Oklahoma, Ontario, Oregon, Pakistan, Palestine, Pennsylvania, Poland, Portugal, Primorye, Prince Edward I., Qinghai, Québec, Rhode I., Romania, Sakhalin, Sardegna, Saskatchewan, Sicilia, Sinai, South Carolina, South Dakota, South European Russi, Spain, Sweden, Switzerland, Tadzhikistan, Taiwan, Tennessee, Texas, Tibet, Transcaucasus, Tunisia, Turkey, Turkey-in-Europe, Turkmenistan, Tuva, Ukraine, Utah, Uzbekistan, Vermont, Vietnam, Virginia, Washington, West Himalaya, West Siberia, West Virginia, Wisconsin, Wyoming, Xinjiang, Yakutskiya, Yugoslavia | |
| Plant parts | Aerial parts | |
| Other cancers | Breast cancer | |
| Target gene or protein | cIAP1, cIAP2, Survivin, p21, Cyclin D1, p-STAT-3, HO-1, IRE1α, p-elF2α, LC3B I, LC3B II | |
| Gene or Protein evidence | Apoptosis protein array and immunoblotting analysis revealed that PA downregulated the pro-survival proteins, including cIAP1, cIAP2, and survivin, leading to cell death of both attached and suspended cells. Interestingly, PA decreased the levels of proteins associated with anoikis resistance, including p21, cyclin D1, p-STAT3, and HO-1. Ectopic expression of active STAT3 attenuated PA-induced anoikis sensitivity. Although PA activated ER stress and autophagy, as determined by increases in the levels of characteristic markers, such as IRE1α, p-elF2α, LC3B I, and LC3B II, PA treatment resulted in p62 accumulation, which could be due to PA-induced defects in autophagy flux. | |
| Target pathways | These data suggest that PA sensitizes metastatic breast cancer cells to anoikis via multiple pathways, such as inhibition of pro-survival pathways and activation of ER stress and autophagy, leading to the inhibition of metastasis. | |
| IC50 | NA | |
| Potency | These findings suggest that sensitization to anoikis by PA could be used as a new therapeutic strategy to control the metastasis of breast cancer. | |
| Cell line/ mice model | MDA-MB-231 cells (human) and 4T1 cells (mouse) | |
| Additional information | In conclusion, our data suggest that PA can act as an effective apoptotic compound in human and mouse metastatic breast cancer cells through the inhibition of Akt, STAT3, and p38 MAPK and activation of the ER stress response. Although, further studies are needed to fully elucidate the molecular mechanism underlying anoikis sensitization, our study suggests that sensitization of cancer cells to anoikis is a useful strategy to prevent tumor metastasis and that PA is one of the candidates for the control of metastasis. | |
| PubChem ID | 15917998 | |
| Additional PMIDs | NA | |
| Additional sources of information | https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:455176-1 | |
| Safety | NA |