Annona coriacea Mart. Fractions Promote Cell Cycle Arrest and Inhibit Autophagic Flux in Human Cervical Cancer Cell Lines

Abstract

Plant-based compounds are an option to explore and perhaps overcome the limitations of current antitumor treatments. Annona coriacea Mart. is a plant with a broad spectrum of biological activities, but its antitumor activity is still unclear. The purpose of our study was to determine the effects of A. coriacea fractions on a panel of cervical cancer cell lines and a normal keratinocyte cell line. The antitumor effect was investigated in vitro by viability assays, cell cycle, apoptosis, migration, and invasion assays. Intracellular signaling was assessed by Western blot, and major compounds were identified by mass spectrometry. All fractions exhibited a cytotoxic effect on cisplatin-resistant cell lines, SiHa and HeLa. C3 and C5 were significantly more cytotoxic and selective than cisplatin in SiHa and Hela cells. However, in CaSki, a cisplatin-sensitive cell line, the compounds did not demonstrate higher cytotoxicity when compared with cisplatin. Alkaloids and acetogenins were the main compounds identified in the fractions. These fractions also markedly decreased cell proliferation with p21 increase and cell cycle arrest in G2/M. These effects were accompanied by an increase of H2AX phosphorylation levels and DNA damage index. In addition, fractions C3 and C5 promoted p62 accumulation and decrease of LC3II, as well as acid vesicle levels, indicating the inhibition of autophagic flow. These findings suggest that A. coriacea fractions may become effective antineoplastic drugs and highlight the autophagy inhibition properties of these fractions in sensitizing cervical cancer cells to treatment.

Screening of antidiabetic and antioxidant potential along with phytochemicals of Annona genus: a review

“…Gomes et al 2019 reported, leaves extract of Annona coriacea has been found to contain palmitic acid, oleic acid, asitrocinone, annonacin, trilobalicin, annomuricin E, asimicin, bullatacin, annohexocin, murihexocin, goniotriocin, bullatalicinone, annoglaucin, ginsenoside Rh5, salzmanolin, annoheptocin A, annoheptocin B, squamocin glycosylated using analysis of the electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry [40].…”

Bioprospecting of Natural Compounds from Brazilian Cerrado Biome Plants in Human Cervical Cancer Cell Lines

“…Among Annona species, in vitro antitumor potential has been demonstrated for many compounds isolated from the essential oils of leaves of A. vepretorum and A. sylvatica [ 28 ]. Different parts of A. squamosa , A. muricata , A. coriacea , and A. cacans plants carry acetogenin compounds which exhibit activity against human cancer cell lines [ 29 , 30 ]. These acetogenin compounds are typically found in Annona sp.…”

Porric acid E, a natural compound from Rhytidhysteron sp. BZM-9, suppresses colorectal cancer growth via an autophagy-dependent pathway

“…Natural anticancer compounds with significant efficacy extracted from plants, microorganisms, and marine organisms have been used in clinical practice 6 . Many natural products have been shown to suppress tumor growth by inducing cell cycle arrest or apoptosis 7 , 8 . Endophytic fungi constitute an enormous and comparatively untapped source of biodiversity that is considered a wellspring of effective novel natural products with potential medical applications 9 .…”