Soursop Leaves (Annona muricata L.) Endophytic Fungi Anticancer Activity against HeLa Cells

Author: Akhmad Endang Zainal Hasan, Heddy Julistiono, Nurliani Bermawie, Eny Ida Riyanti, Fahru Reza Arifni

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Studies have reported that soursop (Annona muricata L.) leaves can be used to treat cervical cancer. This study aims to determine the use of endophytic fungi of A. muricata leaves extract as an ingredient that inhibits cervical cancer. The isolated endophytic fungi from various soursop leave accessions were grown in culture media, then extracted using ethyl acetate. The extract was then tested against anti-yeast, cervical cancer cells, and on normal cells as control using the MTT  method. Five isolated fungi were selected based on the greatest inhibition in one concentration, and the inhibitory concentration 50 (IC50) value was determined.

The soursop leaves endophytic fungi extracts showed cytotoxicity against cervical cancer cells by inhibiting the multiplication of HeLa cancer cells in vitro. The Sir-SM2 endophytic fungi crude ethyl acetate extract showed high cytotoxicity to cervical cancer cells (HeLa cells) but less harmful to the normal Chang cells; therefore can be a natural anticancer. Identification based on morphology shows that the isolated Sir-SM2 endophytic fungi belong to the Penicillium genus, and molecular identification based on Internal Transcribed Spacer shows high similarities with Penicillium crustosum.


Keywords: cervical cancer, endophytic, cytotoxic, ethyl acetate, identification

1. Introduction

Cervical cancer is a type of cancer that causes the fourth highest death in women with cancer. In 2020, new cases estimated 604,000, with 342,000 deaths worldwide (WHO, 2020a). Cervical cancer can be caused by infection due to excess free radical production, apart from human papillomavirus (HPV) (WHO, 2020b).

Commonly performed treatments for patients with cancer are surgery, chemotherapy, hormone therapy, radiation therapy, targeted drug therapy, and immunotherapy (American Cancer Society, 2016). Unfortunately, some of these treatments cause side effects, such as causing hair loss, early menopause, weariness, infections, sores on the mouth and throat, and remembrance problems (Mehta and Bhargava, 2019). On the other hand, herbal medicines and phytochemical derivatives have therapeutic effects. Several studies have shown positive results from herbal medicines in improving the quality of life and increasing the immune system of cancer patients (Lee et al., 2018).  Additionally, medicinal plants with secondary metabolites showing significant antioxidant activity can play a role in cancer treatment (Seca and Pinto, 2018).

Flowering plants in Indonesia consist of 30,000 species, of which 940 species are identified as having medicinal properties, one of which is soursop. The soursop plant is a type of fruit plant that contains bioactive compounds, such as tannins, phytosterols, flavonoids, saponins, and alkaloids (Agu and Okolie, 2017). Antioxidant compounds prevent the type of free radical damage that has been linked to cancer development (Meng et al., 2020). The soursop plant produces acetogenins that exhibit cytotoxic activity against cancer cells and have special affinities for some resistant cells. Acetogenins from Annonaceae are cytotoxic against several cancer and tumor cells, such as pancreatic cancer cells (PACA-2), lung cancer cells (A549), colon, lung, and pancreatic tumors  (Nugraha et al., 2019). Research on Erythrina poeppigiana leaves showed an inhibitory concentration 50 (IC50) value or inhibition against cervical cancer cells (HeLa) of 7.18 μg mL−1 (Herlina et al., 2019). Bioactive compounds may be produced by endophytic microbes.

Endophytic microbes live in plant tissue by forming colonies without harming the host and producing bioactive compounds that have the potential for drug development (Gouda et al., 2016). Gouda et al. (2016) reported that endophytic microbes could synthesize bioactive compounds similar to those produced by their host due to the evolutionary exchange of genetic information. Metabolite compound production through endophytic microbes will reduce the exploitation of the soursop plant; hence, this plant can continue to produce fruit for public consumption. Minarni et al. (2017) reported that extract of endophytic fungi isolated from the A. muricata leaves could suppress the overgrowth of MCF-7 breast cancer cells with an IC50 value of 19.20 ± 7.71 g mL−1. Likewise, Arifni et al. (2017) also reported that soursop leaves endophytic fungi extract has an IC50 value for colon cancer (WiDr) of 20.80 μg mL−1. The endophytic fungi of soursop leaves show significant potential for anticancer activity. Therefore, this study aims to test the endophytic extract activity against cervical cancer cells (HeLa).

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This article has been published in Saudi Journal of Biological Sciences

A. Endang Zainal Hasan, H. Julistiono, N. Bermawie, E. Ida Riyanti, F. Reza Arifni, Soursop Leaves (Annona muricata L.) Endophytic Fungi Anticancer Activity against HeLa Cells, Saudi Journal of Biological Sciences (2022),

PII: S1319-562X(22)00270-4
Reference: SJBS 103354

To appear in: Saudi Journal of Biological Sciences
Received Date: 28 August 2021
Revised Date: 11 May 2022
Accepted Date: 15 June 2022

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