Comparative Study of Antiproliferative Activity in Different Plant Parts of Phaleria macrocarpa and the Underlying Mechanism of Action

Abstract

Phaleria macrocarpa is a medicinal plant widely used in Indonesian folk medicine to treat several diseases, including cancer. However, the comparative evaluation of various plant parts of P. macrocarpa has not been studied for their anticancer properties on breast cancer. The study aimed to assess the antiproliferative activity of the ethanol extract of various parts of Phaleria macrocarpa against T47D human breast cancer cell lines. Several parts of P. macrocarpa, including pericarp, mesocarp, seed, and leaf, were used to determine the most potent plant part to inhibit the growth of T47D cells. The cytotoxic effects of each plant part were evaluated by WST-1 assay. The apoptotic level of T47D cells was determined by annexin V-FITC-PI and DNA fragmentation assay. Propidium iodide staining and the CFSE assay were used to examine the effect of each extract on cell cycle distribution and cell division, respectively. The relative number of caspase-3, Bax, and Bcl-2 was analyzed by flow cytometry technique. WST-1 assay revealed that P. macrocarpa leaves exhibited the most potent antiproliferative activity ( p < 0.05 ) compared to other plant parts with selectivity only to T47D cells. P. macrocarpa leaves extract effectively induced apoptosis, inhibited proliferation, and arrested the cell cycle of T47D cells. The relative number of caspase-3 was significantly ( p < 0.05 ) increased after being treated with P. macrocarpa leaf extract. P. macrocarpa leaf extract also leads to the dose-dependent accumulation in the Bax/Bcl-2 ratio due to upregulation of Bax and downregulation of Bcl-2. The overall results indicated that P. macrocarpa leaves could inhibit the proliferation of T47D cells and trigger apoptosis through caspase-3 activation and Bax/Bcl regulation. Therefore, P. macrocarpa leaves can be used for breast cancer therapy.

Synergistic modulation of proinflammatory mediators and cytokines in lipopolysaccharide-activated RAW 264.7 macrophages: The therapeutic potential of Elephantopus scaber and Sauropus androgynus ethanol extract

“…The leaves of each plant were washed, dried in an oven at 40°C, and ground to a fine powder. The fine powder was macerated in 95% ethanol (1:10) at room temperature (25°C) for 3 days, as described by Christina et al [9] and Christina et al [14]. The mixture was then filtered and evaporated in a rotary evaporator.…”

Evaluation of the anthraquinone drug rhein at IC50 on T-47D breast cancer cell lines based on analytical methods

“…In a study by Chang et al, [10] anthraquinone rhein was purchased from Sigma-Aldrich, the IC50 values of rhein anthraquinone in T-47D/VEC and T-47D/HER2 cells were 36.69 ± 9.77 (129.1 µM) and 30.66 ± 2.21 µg/ml (107.9 µM) after 48 hours of treatment, respectively. However, the effects of this anthraquinone on other cancer cells were also good at different treatment times.…”

“…This intensity indicates cells that have undergone apoptosis. Yuyunika et al [10] showed that Phaleria macrocarpa exhibited anti-proliferative and apoptotic effects on her T-47D cells. Apoptosis or programmed cell death mechanism is considered one of the proposed anti-tumor mechanisms of phenolic compounds [14].…”

“…Regarding rhubarb (Rheum emodi L.) [9], the most common constituents of rhubarb are anthraquinones (i.e., rhein, chrysophanol, aloeemodin, emodin, physion, and their glycosides) and stilbene-resveratrol and their glycosides. showed that Anthraquinones and glycosides exhibit biological and antibacterial activity [10]. Analysis of polyphenols in the study of Wang et al [3] indicates the presence of abundant tannins in rhubarb, which is the basis of rhubarb laxatives.…”

Antiproliferative Potency of God’s Crown Fruit (Phaleria macrocarpa) Extract Against Breast Cancer Cell

“…The god's crown (Phaleria macrocarpa) is a plant often used by Indonesian human beings as a medicinal herb. This herb has compounds that effectiveness in cancer treatment [8][9][10] . Phaleria macrocarpa fruit holds alkaloids, saponins, and polyphenols 11 .…”