Molecular Mechanism of Novel PAMAM Dendrimer Decorated Tectona grandis and Lactobacillus plantarum Nanoparticles on Autophagy-Induced Apoptosis in TNBC Cells.

Autor: Muthukrishnan, Saradhadevi, Gunasangkaran, Gayathiri, Ravi, Anjali K., Amirthalakshmi, Sobiya Ramaraju, Gandhi, Durganjali, Arumugam, Vijaya Anand, Shanmugam, Velayuthaprabhu, Sakthivel, Kunnathur Murugesan, Pushpam, Marie Arockianathan, kaliyaperumal, Ashokkumar, Packiaraj, Gurusaravanan, Muthukrishnan, Arun
Zdroj: BioNanoScience; Sep2024, Vol. 14 Issue 3, p2940-2963, 24p
Abstrakt: Triple-negative breast cancer presents a global health concern due to its prevalence and treatment challenges. The heterogeneity of tumor subtypes and the lack of therapeutic targets contribute to treatment failure, compounded by adverse effects and resistance to conventional treatments. Consequently, there is an urgent need for innovative therapeutic strategies. This study aims to develop a green-synthesized compound by conjugating Tectona grandis and Lactobacillus plantarum with PAMAM dendrimers, evaluating its efficacy against TNBC. The potent bioactive compounds identified, 1-naphthalenecarboxylicacid, -(3-furanyl) ethyl] decahydro-1,4a-didimethyl-6-methylene from T. grandis and 3-phenyl-1,2,4-benzotriazine from L. plantarum, were analyzed through GC-MS. Their interaction with the autophagy gene ATG5 was examined using the PyRX program, demonstrating potential for drug design. Characterization of the synthesized compounds was conducted through UV-Vis spectroscopy, TEM, DLS, Zeta Potential, and FTIR analysis, confirming the formation of negatively charged, polydispersed, multi-branched (5.71–7.54 nm) with an absorption peak at 351 nm nanoparticles (PDTgNP) and positively charged, monodispersed, multi-branched (11–17 nm), absorption peak at 258 nm nanoparticles (PDLpNP). The antitumor efficacy of PDTgNP and PDLpNP was evaluated through MTT assay, scratch assay, DAPI, and double-staining techniques on the MDA-MB-231 cell line, demonstrating dose-dependent cytotoxicity with IC50 values of 43.9 μg/ml and 54.90 µg/ml, respectively, along with its enhanced autophagic and apoptotic efficacy. Additionally, PDTgNP and PDLpNP downregulated LC3 while upregulating ATG3, ATG5, and ATG12 in MDA-MB-231 cells, indicating potential action of autophagy. Therefore, this green synthesis method holds promise as an effective approach, potentially yielding novel promising anticancer agents for the treatment of TNBC. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index