Natural Gallic Acid and Methyl Gallate Induces Apoptosis in Hela Cells through Regulation of Intrinsic and Extrinsic Protein Expression

Abstract

Induction of apoptosis is one of the targeted approaches in cancer therapies. As previously reported, natural products can induce apoptosis in in vitro cancer treatments. However, the underlying mechanisms of cancer cell death are poorly understood. The present study aimed to elucidate cell death mechanisms of gallic acid (GA) and methyl gallate (MG) from Quercus infectoria toward human cervical cancer cell lines (HeLa). The antiproliferative activity of GA and MG was characterised by an inhibitory concentration using 50% cell populations (IC50) by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Cervical cancer cells, HeLa, were treated with GA and MG for 72 h and calculated for IC50 values. The IC50 concentration of both compounds was used to elucidate the apoptotic mechanism using acridine orange/propidium iodide (AO/PI) staining, cell cycle analysis, the Annexin-V FITC dual staining assay, apoptotic proteins expressions (p53, Bax and Bcl-2) and caspase activation analysis. GA and MG inhibited the growth of HeLa cells with an IC50 value of 10.00 ± 0.67 µg/mL and 11.00 ± 0.58 µg/mL, respectively. AO/PI staining revealed incremental apoptotic cells. Cell cycle analysis revealed an accumulation of cells at the sub-G1 phase. The Annexin-V FITC assay showed that cell populations shifted from the viable to apoptotic quadrant. Moreover, p53 and Bax were upregulated, whereas Bcl-2 was markedly downregulated. Activation of caspase 8 and 9 showed an ultimate apoptotic event in HeLa cells treated with GA and MG. In conclusion, GA and MG significantly inhibited HeLa cell growth through apoptosis induction by the activation of the cell death mechanism via extrinsic and extrinsic pathways.

Mentha longifolia L. Inhibits Colorectal Cancer Cell Proliferation and Induces Apoptosis via Caspase Regulation

“…Medicinal herbs are commonly used to treat various ailments, including cancer and malignancies [23,24]. Earlier studies showed that natural products could exhibit several biological activities, such as inducing apoptosis-mediated proliferation inhibition through up-regulation of bax and caspase-3 and down-regulation of bcl2 genes [25][26][27], repressing insulin-like growth factor-1 and inducing Waf-1 gene expression [28,29], glutathione S-transferase activity [30] heat shock protein [31], anti-inflammatory [32,33] and inhibitor of GLI-mediated transcription, a pathway that causes the formation and progression of a variety of tumors [34]. The natural bioactive compound of the Lamiaceae family was also reported to exert anti-proliferative activity, which inhibits oncocyte growth, induction of differentiation, apoptosis, and induces G2/M arrest on cancer cells [35][36][37], and has potential antioxidant, anti-microbe, and anti-inflammatory properties [38,39].…”

Spice-Derived Phenolic Compounds: Potential for Skin Cancer Prevention and Therapy

“…Apart from their natural role, phenolic compounds exhibit notable pharmacological properties that encompass anti-inflammatory [44], immunosuppressive [45], cardioprotective [46], antioxidant [47], neuroprotective [48], and antimicrobial activities [49]. Moreover, several phenolic compounds have shown anticancer activity by inhibiting the growth of cancer cells [50], promoting cell death such as apoptosis [51], autophagy [52], necroptosis [53], or targeting numerous signaling pathways [54][55][56]. In addition, the formation of new blood vessels that support tumor growth has also been reported as a possible target of phenolic compounds [57][58][59].…”