Abstract
Cervical cancer is the third most common in Brazilian women. The chemotherapy used for the treatment of this disease can cause many side effects; then, to overcome this problem, new treatment options are necessary. Natural compounds represent one of the most promising sources for the development of new drugs. In this study, 13 different species of 6 families from the Brazilian Cerrado vegetation biome were screened against human cervical cancer cell lines (CCC). Some of these species were also evaluated in one normal keratinocyte cell line (HaCaT). The effect of crude extracts on cell viability was evaluated by a colorimetric method (MTS assay). Extracts from Annona crassiflora, Miconia albicans, Miconia chamissois, Stryphnodendron adstringens, Tapirira guianensis, Xylopia aromatica, and Achyrocline alata showed half-maximal inhibitory concentration (IC50) values < 30 μg/mL for at least one CCC. A. crassiflora and S. adstringens extracts were selective for CCC. Mass spectrometry (Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (ESI FT-ICR MS)) of A. crassiflora identified fatty acids and flavonols as secondary compounds. One of the A. crassiflora fractions, 7C24 (from chloroform partition), increased H2AX phosphorylation (suggesting DNA damage), PARP cleavage, and cell cycle arrest in CCC. Kaempferol-3-O-rhamnoside and oleic acid were bioactive molecules identified in 7C24 fraction. These findings emphasize the importance of investigating bioactive molecules from natural sources for developing new anti-cancer drugs.
Highlights
Among several cancer types with a higher incidence in Brazil, cancer of the uterine cervix is the third most common in women, excluding non-melanoma skin cancer (NMSC) [1]
Three species showed lower IC50 values in the cancer cell lines listed in Table S1 (Supplementary Materials): Tapirira guianensis (1), Xylopia aromatica (3), and Achyrocline alata (10)
Brazilian flora represents a vast resource for the discovery of substances with biological properties, and studies have shown that extracts from a variety of plants have cytotoxic effects on human tumor cell lines [10,19,25,26]
Summary
Among several cancer types with a higher incidence in Brazil, cancer of the uterine cervix is the third most common in women, excluding non-melanoma skin cancer (NMSC) [1]. In 2018, around 570,000 new cases were estimated, with a mortality of 311,000 women worldwide [2]. In Brazil, mortality in women from this type of cancer follows world estimates, representing the fourth leading cause of cancer death, excluding NMSC [3]. The drugs used in chemotherapy treatment are platinum-based. This treatment can cause many side effects and it has a limited influence on survival in patients with advanced or recurrent cancer [4,5]. New therapeutic options are needed to overcome these problems
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