• Title/Summary/Keyword: insulin-like growth factor receptor (IGFR)

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A Cipadesin Limonoid and a Tirucallane Triterpene from the Fruit of Sandoricum koetjape and their Inhibitory Properties against Receptor Tyrosine Kinases

  • Rachmadhaningtiyas, Dyah Ayu;Heliawati, Leny;Hermawati, Elvira;Syah, Yana Maolana
    • Natural Product Sciences
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    • v.27 no.2
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    • pp.134-139
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    • 2021
  • A new cipadesin limonoid, i.e. 3-epi-cipadonoid C (1), and a new tirucallane triterpene, i.e. hispidol B 3-palmitate (3), have been isolated from the seeds and fruit peels extract of Sandoricum koetjape, respectively. Along with these compounds the known limonoid, cipaferen G (2), and two pentacyclic triterpenes, bryonolic (4) and bryononic (5) acids, were also isolated. The strucrures of the new compounds were elucidated by the analysis of NMR and mass spectral data. Compounds 1 - 5 were evaluated as the inhibitor of receptor tyrosine kinases (EGFR, Epidermal Growth Factor Receptor; HER2, HER4, Human Epidermal growth factor Receptor 2, -4; IGFR, Insulin-like Growth Factor Receptor; InsR, Insulin Receptor; KDR, Kinase insert Domain Receptor; PDGFRα, and PDGFRβ, Platelet-Derived Growth Factor Receptor-α and -β). The results showed only 1 and 3 that have weak activity against InsR.

Effects of Pinelliae Rhizoma(PR) on Ovarian Tissue in Polycystic Ovary Syndrome(PCOS) Rats (반하(半夏)가 다낭성 난소 증후군이 유발된 흰쥐의 난소 조직에 미치는 영향)

  • Yeo, Eun-Ju;Jo, Sung-Hee;Yang, Seung-Jung;Park, Kyung-Mi
    • The Journal of Korean Obstetrics and Gynecology
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    • v.25 no.2
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    • pp.66-77
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    • 2012
  • Objectives: This study was designed to investigate the effects of PR on ovarian tissue in PCOS rats through measurement of morphological and histo-pathological observations, ovarian size. In addition, effects on expression levels of Insulin like Growth Factor Receptor(IGFR) were also investigated to elucidate related mechanisms. Methods: PCOS was induced by single intermuscular injection with ${\beta}$-Estradiol 17-Valerate(EV) in female rats. Normal group(NOR, n=8) were injected with sesame oil and administrated hard food for five weeks. Control group(CTL, n=8) were injected with EV and administrated hard food for five weeks. CR group(n=8) were injected with EV and administrated hard food mixed CR for five weeks. Then, we measured weights of body and ovary, uptakes of food and water. And we observed morphological and histo-pathological changes of ovary, levels of IGFR. Results: In this experiments, single injection of Estradiol Valerate(EV) induced suppression of weight gain, formation of cysts, increase of IGFR expression. Oral administration of PR prevent decrease of ovarian size significantly. Further more, formation of cystic follicles induced by EV injection is suppressed by PR treatment. Conclusions: These results suggest PR can be used for patients with PCOS to prevent formation of cystic follicles and malfunction of ovary.

Bidirectional Cross-talk Between Estrogen Receptor and Growth Factor Receptors in Breast Cancer Cell (유방암세포에서 에스트로겐 수용체와 성장인자 수용체 사이의 양방향 상호작용)

  • Min, Gyesik
    • Journal of Life Science
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    • v.28 no.2
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    • pp.265-273
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    • 2018
  • Estrogen (E2) is involved in the development and progression of breast cancer and is mediated by estrogen receptor (ER). ER plays important roles in cellular proliferation, migration, invasion and causing drug resistance through diverse cross-talks with epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathways in breast cancer cells. Breast cancer is caused mainly by break-down of homeostasis of endocrine signaling pathways especially by the uncontrolled expression and increased activities of E2/IGF-1/EGF, ER/G-protein estrogen receptor (GPER)/IGF-1R/EGFR and their intracellular signaling mediators. These changes influence the complex cross-talk between E2 and growth factors' signaling, eventually resulting in the progression of cancer and resistance against endocrine regulators. Thus, elucidation of the molecular mechanisms in stepwise of the cross-talk between E2 and growth factors will contribute to the customized treatment according to the diverse types of breast cancer. In particular, as strategies for the treatment of breast cancer with diverse genotypes and phenotypes, there can be use of aromatase inhibitors and blockers of E2 action for the ER+ hormone-dependent breast cancer cells and use of IGF-1R/EGFR activity blockers for suppression of cancer cell proliferation from the cross-talk between E2 and growth factors. Furthermore, changes in the expression of the ECM molecules regulated by the cross-talk between ER and EGFR/IGF-1R can be used for the targeted therapeutics against the migration of breast cancer cells. Therefore, it is required for the cross-talk among the signaling pathways of ER, GPER, IGF-1R and EGFR concerning cancer progression to be elucidated in more detail at the molecular level.