An Integrated Study on the Antitumor Effect and Mechanism of Triphala Against Gynecological Cancers Based on Network Pharmacological Prediction and In Vitro Experimental Validation

Abstract

Objectives. Triphala is a herbal medicine that has been widely used for treating a variety of ailments. This study aims to systematically analyze the antitumor effects of Triphala on gynecological cancers. Methods. The antineoplastic activities of Triphala on gynecological cancers were analyzed using network pharmacology-based strategies. Afterward, the human ovarian cancer cell line SK-OV-3, cervical cancer cell line HeLa, and endometrial cancer cell line HEC-1-B were selected for experimetal valification. Results. Network pharmacology analysis suggested that Triphala could comprehensively intervene in proliferation and apoptosis through diverse signaling pathways, mainly including MAPK/ERK, PI3K/Akt/mTOR, and NF-κB/p53. The Cell Counting Kit 8 (CCK-8) assay illustrated that Triphala was able to inhibit cell proliferation with half inhibition concentration (IC50) values of 98.28 ± 13.71, 95.56 ± 8.94, and 101.23 ± 7.76 µg/mL against SK-OV-3, HeLa, and HEC-1-B cells, respectively. The ELISA experiment demonstrated that Triphala was capable of promoting programmed cell death, with dosage correlations. The antiproliferative and proapoptotic activities were confirmed by flow cytometric analysis using Ki67 antibody and Annexin V/propidium iodide (PI) dual staining. Western blotting revealed a decrease in expression levels of phospho-Akt, phospho-p44/42, and phospho-NF-κB p56 in cells administered Triphala, which indicated that the possible mechanism could involve downregulation of MAPK/ERK, PI3K/Akt/mTOR, and NF-κB/p53 signaling pathways, as was predicted. Conclusion. Triphala holds great promise for treating gynecological cancers. Although the favorable pharmacological properties have been preliminarily investigated in this study, further studies are still needed to uncover the sophisticated mechanism of Triphala in cancer therapy.

Oxidative Stress and Cancer: Chemopreventive and Therapeutic Role of Triphala

“…The antiproliferative and proapoptotic activities were confirmed by cell cycle analysis and expression of Ki-67 protein. It was also found that Triphala decreased the expression of phospho-Akt, phospho-p44/42, and phospho-NF-κB p56 in these gynecological cancer cells, which indicated that MAPK/ERK, PI3K/Akt/mTOR, and NF-κB/p53 signaling pathways were the possible mechanism of Triphala-induced apoptosis [60]. Besides its anti-proliferative and apoptotic effects, Triphala suppressed cell migration of cancer cells in vitro thus indicating its anti-metastatic potential [58].…”

“…[59] Inhibits proliferation of gynecological cancers cell with IC50 values of 98.28-101.23 µg/mL against SKOV-3, HeLa, and HEC-1B cells. [60] Inhibits proliferation of HeLa, PANC-1, and MDA-MB-231 cells and suppresses the clonogenicity of HeLa cells. [61] Inhibits proliferation of HCT116 and HCCSCs cells independent of p53 status.…”

“…Extensive studies on Triphala have shown that it has preventive and therapeutic efficacy against malignancies such as breast, colon, pancreas, prostate, ovarian, cervical, endometrial, and lymphatic cancers as well as melanoma [58,60,61,63,74]. Although Triphala has been used for centuries against various ailments, recent in vitro, in vivo and human studies have demonstrated its safety and efficacy against multiple diseases including cancer.…”

Cancer Cytotoxic and Anti-HIV Potential of Triphala Herb Mixture on from Chae Son, Lampang, Thailand

“…(TC), also known as the 'Triphala'. The proportion of 1:1:1 or even 1:1:2, each of which consists of a variety of structurally varied chemicals [1]. Triphala is traditionally been used as laxative in chronic constipation, colon cleansing, digestion problems and poor food assimilation [2,3].…”

Triphala Suppresses Growth and Migration of Human Gastric Carcinoma Cells In Vitro and in a Zebrafish Xenograft Model

“…Roxb, and Phyllanthus emblica Linn., is a widely prescribed traditional remedy that has been clinically used for thousands of years as treatment of various diseases and disorders. Numerous publications indicate that Triphala exerts potent antineoplastic activities against different types of cancer, including breast, colon, pancreas, prostate, ovarian, cervical, endometrial, and lymphatic cancer as well as melanoma [4, 5]. However, whether Triphala has similar effects on gastric cancer has not yet assessed in relevant reports.…”