Anticancer activity of Piper cubeba L. extract on triple negative breast cancer MDA-MB-231

Abstract

Context: Piper cubeba L. (family Piperaceae) is used traditionally for the treatment of many diseases, including cancer. Aims: To determine the anticancer activity of P. cubeba crude extracts on cancer cells and identify chemical constituents of the active fraction. Methods: Seeds of P. cubeba were sequentially extracted with dichloromethane followed by methanol and purified using column chromatography. Fractions were screened the cytotoxicity against triple negative breast cancer (MDA-MB-468) using MTT assay. Then, active fractions were evaluated cytotoxicity against breast cancer (MCF-7 and MDA-MB-231), colon cancer (HT-29), cholangiocarcinoma (KKU-M213) and normal fibroblast (L929) cells. Total phenolic, tannin, and flavonoid contents of active fraction were investigated, and the chemical composition was analyzed using GC-MS. Flow cytometry was applied to determine the cell cycle, apoptosis, and evidence of caspase activation. Results: Fraction DE14 and DE15 showed cytotoxic activity against MDA-MB-468. Fraction DE15 exhibited the most potent cytotoxicity against MDA-MB-231, KKU-M213, HT-29 and L929. As the fraction DE15 was of dichloromethane extraction, major contents were nonpolar fatty acids and fatty acid esters, followed by propylene glycol and hydrocarbons. The phenolic compounds were however traceable, leading to their measurable antioxidant property. This extract did not cause cell cycle arrest on MDA-MB-231. However, fraction DE15 significantly increased apoptotic cells at 48 and 72 h, and significantly induced multi-caspases activity on MDA-MB-231 in a time-dependent manner. Conclusions: Fraction DE15 exhibited cytotoxicity effect and induced apoptosis on triple negative breast cancer and showed less toxicity on normal fibroblast cells.

Evaluation of In Vitro Cytotoxic Property Against Cholangiocarcinoma Cell Line and GC/MS Analysis from Leaf of Erythrophleum succirubrum Gagnep

“…While Janeklang et al, (2014) found that tiliacorinine had an antiproliferative effect on human cholangiocarcinoma cell lines, with IC 50 values ranging from 2.59 to 7.00 µg/mL. Compared with the results of Janeklang et al, (2014), Tedasen et al, (2020) and Maungchanburi et al, (2022) extract is generally examined for in vitro cytotoxic activity if the IC 50 value in the carcinoma cells 48 -72 h after incubation is less than 20 µg/mL, and for pure compounds when the IC 50 is less than 4 µg/mL (Boik, 2001). Even though the exposure time in this experiment was 96 h, our finding might imply that E. succirubrum may have strong cytotoxic activity against CCA.…”

“…Piperine-free Piper nigrum L. extract, exerted a cytotoxic effect against KKU-M213 cells, with an IC 50 value of 13.70 ± 1.14 µg/ mL (Tedasen et al, 2020). Maungchanburi et al, (2022) reported that fraction DE15 from dichloromethane extract of Piper cubeba L. seed had cytotoxic activity against cholangiocarcinoma cell line KKU-M213 with an IC 50 value of 6.76 ± 0.52 µg/mL. While Janeklang et al, (2014) found that tiliacorinine had an antiproliferative effect on human cholangiocarcinoma cell lines, with IC 50 values ranging from 2.59 to 7.00 µg/mL.…”

In vitro antioxidant properties and antimicrobial activity of the ethanolic extract of Senecio nutans Sch. Beep. (Asteraceae)

“…The experiment was performed in triplicate, and the absorbance's were measured at a wavelength of 750 nm (Spectrophotometer Peak Instrumental, model C-7100, USA). The total polyphenolic content was expressed in mg of gallic acid equivalent (GAE)/g of ethanolic extract (Maungchanburi et al, 2022).…”

Cubeb (Piper cubeba L.f.): A comprehensive review of its botany, phytochemistry, traditional uses, and pharmacological properties

“…Copaene, another example, was detected only at the ethanol extract with 13.47% ( 18 ). Propylene glycol dominated the dichloromethane with 23.82%; however, it was not found in all other extracts ( 19 ). These differences might be attributed to the different extraction methods, detection techniques as well as geographic distribution and genetic chemotypes.…”

“…They include dodecanoic acid (lauric acid, 24.05%), hexadecanoic acid (palmitic acid, 11.37%), 9-octadecenoic acid (10.00%), decanoic acid (capric acid, 2.62%), 9,12-octadecadienoic acid (Z,Z) (2.50%), octadecanoic acid (2.08%), methyl decanoate (capric acid methyl ester, 1.80%), tetradecanoic acid (myristic acid, 1.66%), ethyl-(R,E)-4-hydroxy-3-methylpent-2-enoate (1.12%), along with other compounds where their concentrations did not exceed a relative abundance of 1 like palmitic acid methyl ester (0.65%) and octanoic acid (caprylic acid) (0.18%) ( 19 ). The dichloromethane fraction gave the presence of two phenolic compounds which are 4-vinylphenol and 2,4-bis(1,1-dimethylethyl)-Phenol ( 19 ). Besides, several flavonoids and phenolic acids were isolated from the aqueous extract of P. cubeba fruits such as rutin, catechin, gallic acid, caffeic acid, syringic acid, ferulic acid ( 20 , 21 ).…”