02239nas a2200241   4500008004100000022001400041245017700055210006900232260000800301300001100309490000800320520138100328653001501709653001701724653000801741653001601749653002001765100002101785700001901806700001901825700002101844856013201865       2020                        eng d  a0960-076000a6 alpha-Hydroxy-4[14], 10[15]-guainadien-8 beta, 12-olide induced cell cycle arrest via modulation of EMT and Wnt/beta-catenin pathway in HER-2 positive breast cancer cells0 a6 alphaHydroxy414 1015guainadien8 beta 12olide induced cell cycl  cMAR  a1055140 v1973 a<p>Cyathocline purpurea has potential biological activities and has been widely used in traditional Chinese and Ayurvedic medicine. The aim of the present study is to elucidate the anticancer effect of its 6 alpha-hydroxy-4[14], 10 [15]-guainadien-8 beta, 12-olide (SRCP1) against HER-2 positive subtype of breast carcinoma. Anticancer effect of SRCP1 was assessed by cell viability, senescence, apoptosis, cell cycle, DNA synthesis, and gene expression assays. The activity was further validated by the molecular docking study. SRCP1 inhibits human HER-2 positive breast cancer growth via inhibition of DNA synthesis in a dose-dependent manner. SRCP1 induces cell cycle arrest at G(2)/M phase, late apoptosis, and necrosis. Further, it induces senescence causing reduction in migration via down-regulation of EMT. A remarkable increase in the number of necrotic cells and Annexin-V staining revealed that exposure to SRCP1 triggers late apoptosis. Treatment with SRCP1 increased E-cadherin, p21, p53, ER-alpha expression and decreased beta-catenin, MMP-9, snaill, TNF-alpha expression. SRCP1 showed binding affinity towards an active site of the HER-2 receptor. Our results of molecular docking and biological assays demonstrated the potent anticancer activity of SRCP1 in MDA-MB-453 cells via multiple pathways including EMT, TNF-alpha, and Wnt/beta-catenin signaling.</p>
10aAnticancer10abeta-Catenin10aEMT10aGuaianolide10aHER-2 inhibitor1 aJavir, Gitanjali1 aJoshi, Kalpana1 aKhedkar, Vijay1 aRojatkar, Supada  uhttps://library.ncl.res.in/content/6-alpha-hydroxy-414-1015-guainadien-8-beta-12-olide-induced-cell-cycle-arrest-modulation-emt02221nas a2200313   4500008004100000022001400041245010600055210006900161260000800230300001100238490000700249520122400256653001501480653000801495653001101503653002201514653003601536653002001572100002501592700002101617700002401638700001901662700001901681700001601700700001701716700002101733700002101754856013201775       2023                        eng d  a0968-089600aIdentification of new modulator of DNA repairing pathways based on natural product (±)-peharmaline A0 aIdentification of new modulator of DNA repairing pathways based   cAUG  a1173650 v913 a<p>
	The complex heterogenic environment of tumour mass often leads to drug resistance and facilitate chemo insensitivity triggering more malignant phenotypes among cancer patients. Major DNA-damaging cancer drugs have been consistently proven unsuccessful in terms of elevating chemo-resistance. (&amp; PLUSMN;)-peharmaline A, a hybrid natural product isolated from seeds of Peganum harmala L. possesses significant cytotoxic activities. Herein, we have described the design, and synthesis of a novel library of close and simplified analogues around the anticancer natural product (&amp; PLUSMN;)-peharmaline A and investigated their cytotoxic activities, which led to the identification of three structurally simplified lead compounds exhibiting better potency than parent natural product. Among them, demethoxy analogue of peharmaline A was further investigated for its anticancer potential eliciting demethoxy analogue as potent DNA-damage inducing agent attenuating the expression of the proteins responsible for the DNA damage repair. Therefore, this demethoxy analogue warrants detailed investigations for the confirmations of the molecular mechanism-based studies responsible for its anticancer activity.</p>
10aDNA damage10aEMT10aPictet10aSpengler reaction10aStructure-activity relationship10aTotal synthesis1 aKulkarni, Akshay, S.1 aDash, Anshurekha1 aShingare, Rahul, D.1 aChand, Jagdish1 aManhas, Diksha1 aSingh, Aman1 aNandi, Utpal1 aGoswami, Anindya1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/identification-new-modulator-dna-repairing-pathways-based-natural-product-%C2%B1-peharmaline