Cytotoxic Property of Grias neuberthii Extract on Human Colon Cancer Cells: A Crucial Role of Autophagy

Abstract

Traditional herbal medicine has become an important alternative in the treatment of various cancer types, including colon cancer, which represents one of the main health problems around the world. Therefore, the search for new therapies to counteract this disease is very active. Grias neuberthii is an endemic plant located in the Ecuadorian Amazon region, which has been used in traditional medicine for its pharmacological properties, including its ability to inhibit tumor cell growth, although scientific studies are limited. We have analyzed the effect of this plant on two colon carcinoma cell lines, that is, RKO (normal p53) and SW613-B3 (mutated p53) cells. Among several extracts obtained from various parts of G. neuberthii plant, we identified the extract with the greatest cytotoxic potential, derived from the stem bark. The cytotoxic effect was similar on both cell lines, thus indicating that it is independent of the status of p53. However, significant differences were observed after the analysis of colony formation, with RKO cells being more sensitive than SW613-B3. No evidence for apoptotic markers was recorded; nevertheless, both cell lines showed signs of autophagy after the treatment, including increased Beclin-1 and LC3-II and decreased p62. Finally, three chemical compounds, possibly responsible for the effect observed in both cell lines, were identified: lupeol (1), 3′-O-methyl ellagic acid 4-O-β-D-rhamnopyranoside (2), and 19-α-hydroxy-asiatic acid monoglucoside (3).

Pharmacology and Phytochemistry of Ecuadorian Medicinal Plants: An Update and Perspectives

“…It is very well known that some of the most used drugs in cancer chemotherapy derive from natural products. In this context, the high antiproliferative effects shown by the extracts of some plants, such as Annona montana [15] and Grias neuberthii [72], against several human tumor cell lines are of great interest. Isolated compounds with potent in vitro cytotoxic properties include the flavonoid tricin (52) from Huperzia spp.…”

“…No evidence for apoptotic markers was recorded; nevertheless, both cell lines showed signs of autophagy after the treatment, including increased Beclin-1 and LC3-II and decreased p62. Lupeol (37), 3 -O-methyl ellagic acid 4-O-β-D-rhamnopyranoside (38), and 19-α-hydroxyasiatic acid 27-O-β-D-glucopyranoside (39) (Figure 7) were identified as the compounds that were likely responsible for the activity [72]. Five quercetin glycosides and one kaempferol glycoside were isolated from hydroalcoholic extracts of leaves and flowers.…”

“…The main compounds that were present in the hydrolate were 6-methyl-5-hepten-2-one (63.7-64.4%) and linalool (6.5-6.0%). Five lignans were isolated from the nonvolatile fraction and identified as (-)-beilshminol B ( 69), (-)-grandisin ( 70), (-)-3 ,4 -methylenedioxy-3,4,5trimethoxy-7,7 -epo-xylignan ( 71), (-)-3 ,4 -methylenedioxy-3,4,5,5 -tetramethoxy-7,7epoxylignan (72), and (-)-3,4,3 ,4 -dimethylene-dioxy-5,5 -dimethoxy-7,7epoxylignan (73) (Figure 10) [91].…”

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

“…Punicalagin (1-30 µg/mL) increased LC3 II cleavage and the formation of autophagosomes in human U87MG glioma cells, by the activation of AMPK and p27 [240]. Recently, it was also shown that Grias nuberthii extract (20-50 µg/mL), which contains lupeol, 3 -O-methyl ellagic acid 4-O-β-D-rhamnopyranoside, and 19-α-hydroxy-asiatic acid monoglucoside, inhibited the growth of human colon cancer (RKO and SW613-B3) cells by inducing autophagy only (increase in Beclin 1, LC3 II and decrease in p62) [241]. It was also reported that ellagic acid (10-100 µM) inhibited the growth of human ovarian cancer cells (ES-2 and PA-1) by blocking the cell cycle at the G1 phase and by inducing apoptosis.…”

Antioxidant, Cytotoxic and larvicidal Potential in Oxalis latifolia Kunth. Methanolic Leaf Extract

“…Colon cancer (HT-29) positions third as far as frequency, yet second as far as mortality and its expanding in Central and South America because of a continuous progress towards more elevated levels of human turn of events [2]. Colon cancer is the second most common cancer in females and also third in males [3].…”