Description[ edit ] It is a woody perennial bush-like tree meters in height. Its stems are erect and covered in small hairs called trichomes. Its oblong, leathery, blueish-green leaves lack distinct petioles and are blunt or notched at their tips. The leaves are long by centimeters wide. Its flowers are solitary on 3 centimeter long peduncles.

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Annona coriacea Mart. The purpose of our study was to determine the effects of A. 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. 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. Keywords: natural compounds, cervical cancer, autophagy, cell cycle arrest 1.

Introduction Cervical cancer is the fourth most common cancer among women worldwide, accounting for 7. The number of diagnosed cases is about twice as high in developing countries, such as Brazil, where cervical cancer corresponds to the third most common type among Brazilian women [ 2 ]. Despite the high incidence, cervical cancer is one of the tumor types that present significant potential for prevention [ 3 ]. Nevertheless, many cases are still diagnosed at an advanced stage, and the therapeutic options are limited [ 4 ].

So far, platinum-based chemotherapy remains the only anticancer approach that has improved the results in recurrence and metastatic cervical cancer [ 5 ]. However, cisplatin demonstrated extensive side effects, such as myelosuppression and nephrotoxicity, as well as problems related to the resistance and relapse of the disease [ 5 ]. Currently, results with molecular-targeted therapies constitute potential alternatives, but the clinical outcomes are still in progress [ 6 ].

In this context, natural compounds offer an exciting option to explore and maybe overcome the treatment limitations for cervical cancer. Autophagy is a homeostatic biological process that maintains cell survival by recycling organelles and molecules, but its role in cancer is still unclear [ 7 ]. Autophagic process is activated in many tumors and, when inhibited, can lead to cell death or survival, depending on the tissue type, tumor grade, and therapy [ 8 ]. In cervical cancer, autophagy activation is reported as a target of paclitaxel Taxol , a relevant natural product in cancer chemotherapy resistance [ 9 ].

Autophagy targeting has been recognized as a novel therapeutic approach. So far, the establishment of news autophagy modulators is required for cancer treatment [ 10 ]. Annonaceae is a common Brazilian plant family, with 29 genera and approximately species [ 11 ]. Some species of Annonaceae, a family of plants widely distributed in Brazil, have been related by their biological activity as an anticancer, analgesic, and antimicrobial [ 12 , 13 ].

Among the biological activities already reported for the species are analgesic, anti-inflammatory, carminative, and anthelmintic activity [ 15 ]. Recently, methanolic extract of A. Although the advantage of obtaining and developing a therapy from leaves rather than other plant parts is clear, potential cytotoxicity activity from A.

The goal of the current study was to evaluate the antineoplastic activity of seven fractions of leaves of A. We analyzed several biological effects, such as cytotoxicity, proliferation, cell death by apoptosis and autophagy, cell migration, and tumorigenesis, to explore their potential in cervical cancer treatment. Results 2. Anonna coriacea Mart. Supplementary Table S1 summarizes the major features of the seven fractions isolated.


Annona coriacea



EPPO Global Database


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