Journal
LIFE SCIENCES
Volume 307, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2022.120876
Keywords
Apoptosis; Asiatic acid; Breast cancer; Cytotoxicity; Polymeric nanoparticles
Funding
- UGC, India [2061430759, 2210612014 (i) EU-V, 351235]
- Jadavpur University, India [R-11/13/20]
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Asiatic acid (AA), an aglycone of pentacyclic triterpene glycoside, has anticancer effects by inhibiting cellular proliferation and inducing apoptosis. AA-loaded poly lactic-co-glycolic acid (PLGA) NPs (AA-PLGA NPs) showed dose-dependent cytotoxicity and pro-apoptotic properties in breast cancer cells. In vivo studies in mice confirmed the reduced tumor volume and increased caspase-3 expression with AA-PLGA NPs treatment.
Asiatic acid (AA), an aglycone of pentacyclic triterpene glycoside, obtained from the leaves of Centella asiatica exerts anticancer effects by inhibiting cellular proliferation and inducing apoptosis in a wide range of carcino-genic distresses. However, its chemotherapeutic efficacy is dampened by its low bioavailability. Polymeric nanoparticles (NPs) exhibit therapeutic efficacy and compliance by improving tissue penetration and lowering toxicity. Thus, to increase the therapeutic effectiveness of AA in the treatment of breast cancer, AA-loaded poly lactic-co-glycolic acid (PLGA) NPs (AA-PLGA NPs) have been formulated. The AA-PLGA NPs were characterized on the basis of their average particle size, zeta potential, electron microscopic imaging, drug loading, and entrapment efficiency. The NPs exhibited sustained drug release profile in vitro. Developed NPs exerted dose -dependent cytotoxicity to MCF-7 and MDA-MB-231 cells without damaging normal cells. The pro-oxidant and pro-apoptotic properties of AA-PLGA NPs were determined by the study of the cellular levels of SOD, CAT, GSH-GSSG, MDA, protein carbonylation, ROS, mitochondrial membrane potential, and FACS analyses on MCF-7 cells. Immunoblotting showed that AA-PLGA NPs elicited an intrinsic pathway of apoptosis in MCF-7 cells. In vivo studies on female BALB/c mice exhibited reduced volume of mammary pad tumor tissues and augmented expression of caspase-3 when administered with AA-PLGA NPs. No systemic adverse effect of AA-PLGA NPs was observed in our studies. Thus, AA-PLGA NPs can act as an efficient drug delivery system against breast cancer.
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