Lycopene-rich extract from red guava ( Psidium guajava L.) displays cytotoxic effect against human breast adenocarcinoma cell line MCF-7 via an apoptotic-like pathway

Abstract

This study investigated a lycopene-rich extract from red guava (LEG) for its chemical composition using spectrophotometry, mass spectrometry, attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), and computational studies. The cytotoxic activity of LEG and the underlying mechanism was studied in human breast adenocarcinoma cells (MCF-7), murine fibroblast cells (NIH-3T3), BALB/c murine peritoneal macrophages, and sheep blood erythrocytes by evaluating the cell viability with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and flow cytometry. Spectrophotometry analysis showed that LEG contained 20% of lycopene per extract dry weight. Experimental and theoretical ATR-FTIR suggests the presence of lycopene, whereas MS/MS spectra obtained after fragmentation of the molecular ion [M] of 536.4364 show fragment ions at m/z 269.2259, 375.3034, 444.3788, and 467.3658, corroborating the presence of lycopene mostly related to all-trans configuration. Treatment with LEG (1600 to 6.25μg/mL) for 24 and 72h significantly affected the viability of MCF-7 cells (mean half maximal inhibitory concentration [IC]=29.85 and 5.964μg/mL, respectively) but not NIH-3T3 cells (IC=1579 and 911.5μg/mL, respectively). Furthermore LEG at concentrations from 800 to 6.25μg/mL presented low cytotoxicity against BALB/c peritoneal macrophages (IC≥800μg/mL) and no hemolytic activity. LEG (400 and 800μg/mL) caused reduction in the cell proliferation and induced cell cycle arrest, DNA fragmentation, modifications in the mitochondrial membrane potential, and morphologic changes related to granularity and size in MCF-7 cells; however, it failed to cause any significant damage to the cell membrane or display necrosis or traditional apoptosis. In conclusion, LEG was able to induce cytostatic and cytotoxic effects on breast cancer cells probably via induction of an apoptotic-like pathway.

Anti-cancer therapeutic benefit of red guava extracts as a potential therapy in combination with doxorubicin or targeted therapy for triple-negative breast cancer cells

“…Here we have shown that extracts from red guava fruit can induce cell death in TNBC cells. Most studies have shown that guava extracts induce large amounts of apoptotic death in various cancer cells [7,22,31]. Our study, in contrast, found that red guava extracts induce apoptotic and necrotic cell death in TNBC.…”

“…A previous study showed that extracts purified from guava fruit do not have anti-cancer activity in breast cancer cells [21]. However, extracts obtained from lycopene-rich red guava fruit can inhibit ER-positive breast cancer growth [22]. Here we also found that extracts purified from red guava fruit can inhibit TNBC growth, with LMW extracts and total extracts having similar cytotoxic effects on these cells.…”

“…Guava extracts are suggested to have estrogen-like activity, and, therefore, guava extracts are useful for treating ER-positive breast cancer cells, such as MCF-7 cells [19]. Although aqueous extracts of guava fruit may not display effective anti-cancer activity [21], lycopene-rich extracts from red guava fruit can induce apoptosis-like cell death among ER-positive breast cancer cells [22]. Thus different guava species have different bioactive components that result in different activities.…”

Vitamin and bioactive compound diversity of seven fruit species from south Brazil

“…The antioxidant property is responsible for its beneficial effects on human health. 31 Pitanga 1 presented the highest content for this carotenoid with 0.1876 g kg −1 (0.029 g kg −1 fw). This fruit presented higher levels than papaya (0.022 g kg −1 fw) 28 and exhibited lower content than watermelon and tomatoes.…”

“…Lycopene is a powerful antioxidant carotenoid, and its potent antioxidant activity of lycopene is generally responsible for the protection of cellular systems from a variety of reactive oxygen‐nitrogen species. The antioxidant property is responsible for its beneficial effects on human health . Pitanga 1 presented the highest content for this carotenoid with 0.1876 g kg −1 (0.029 g kg −1 fw).…”