Emetine and Its Derivatives as Anticancer Agents Targeting the PI3K/AKT/mTOR Pathway - A Narrative Review of Mechanisms, Pharmacology, and Clinical Insights

Sep 22, 2026

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Emetine (EMT), a naturally occurring tetrahydroisoquinoline alkaloid, exhibits diverse biological actions with anticancer potential. Existing evidence leaves the contributions of EMT derivatives to cancer largely insufficient, especially regarding PI3K/AKT/mTOR signalling. This narrative review synthesizes mechanistic, pharmacological, and clinical insights across multiple cancer types, using sources including PubMed, Scopus, and Web of Science. Results indicate pathway suppression with reported IC50 values between 0.0244 and 1 μM, alongside additional antiviral, antiparasitic, and contraceptive relevance. Preclinical findings suggest selective cytotoxicity at low concentrations, but dose-dependent cardiotoxicity and emetic effects at higher doses require careful optimization. Clinical support remains limited, supporting EMT as a preclinically active candidate for further translational study.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Introduction

Cancer burden and contributing factors

Role of the PI3K/AKT/mTOR pathway in cancer

PI3K/AKT/mTOR signalling components and activation

Therapeutic targeting and inhibitor-related adverse effects

Rationale for natural products and EMT derivatives

Journal of Cellular and Molecular Medicine REVIEW OPEN ACCESS Emetine and Its Derivatives as Anticancer Agents Targeting the PI3K/AKT/mTOR Pathway: A Narrative Review of Mechanisms, Pharmacology, and Clinical Insights Mst. Ismatara Khatun1 | Samy Selim2 | Asif Hassan Malik3 | Md. Sakib Al Hasan4,5 | Abul Bashar Ripon Khalipha4 | Noshin Tasnim Yana4,5 | Mohammad Y. Alshahrani6,7 | Md. Arif Hossain4 | Imam Hossen Rakib4,5 | Anike Chakrabarty8 | Emon Mia4,5 1Department of Pharmacy, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore, Bangladesh | 2Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia | 3Department of Chemistry, York College of The City University of New York (CUNY), Jamaica, New York, USA | 4Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj, Bangladesh | 5Alor Dishari Research Organization, Dhaka, Bangladesh | 6Central Labs, King Khalid University, Abha, Saudi Arabia | 7Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia | 8Department of Biotechnology, Faculty of Engineering and Science, University of Greenwich, Kent, UK Correspondence: Md. Sakib Al Hasan ([mdsakibalhasan192412@gmail.com](mdsakibalhasan192412@gmail.com)) | Abul Bashar Ripon Khalipha ([khalipha1982@gmail.com](khalipha1982@gmail.com)) Received: 8 January 2026 | Revised: 7 August 2026 | Accepted: 12 August 2026 Keywords: Anticancer | Emetine | Literature review | PI3K-AKT-mTOR pathway | toxicity ABSTRACT Emetine (EMT), a naturally occurring tetrahydroisoquinoline alkaloid, shows diverse biological actions, including anticancer effects. Despite existing studies, the role of EMT derivatives in cancer, particularly in relation to the PI3K/AKT/mTOR signalling pathway, remains largely underexplored. This review explores the potential of EMT in targeting PI3K/AKT/mTOR molecular pathways across different cancer types. Data were collected from reliable and well-established sources, including PubMed, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. Findings showed that EMT derivatives suppress PI3KAKT-mTOR pathway activity in multiple cancers such as liver, gastric, acute myeloid leukaemia (AML), and brain, with IC50 values ranging from 0.0244 to 1 μM. Beyond its anticancer activity, EMT showed broad pharmacological relevance, including antiviral, antiparasitic, and contraceptive activities. Preclinical assessments suggest preferential cytotoxicity toward cancer cells at low concentrations; however, known dose-dependent adverse effects, including cardiotoxicity and emetic responses at higher doses, necessitate careful dose optimization before clinical translation. Clinical evidence remains insufficient, and EMT should be considered a preclinically active compound warranting further rigorous translational investigation. 1 | Introduction Cancer is the uncontrolled growth and development of cells in the body, and is one of the foremost reasons for deaths throughout the world [1] . According to the International Agency for Research on Cancer (IARC), there were close to 20 million new cases of cancer in the year 2022 alongside 9.7 million deaths from cancer, with demographics-based predictions indicating that the number of new cases of cancer will reach 35 million by 2050 [2] . Environmental, exogenous and endogenous factors, as well as individual factors including genetic predisposition, contribute to the development of cancer. In addition, smoking, excessive alcohol consumption, diet, and reproductive behaviour are important for the development of malignant neoplasia in the human population [3] . However, several pathways are involved in cancer progression, and one of the key pathways implicated in cancer This is an open access article under the terms of the Creative Commons Attribution Lic

FAQs

What cancer-related role does the PI3K/AKT/mTOR pathway play?

The pathway regulates cell proliferation, differentiation, metabolism, and cytoskeletal reorganization linked to apoptosis and cancer cell survival. It is hyperactivated or altered in many cancer types and supports processes such as survival, growth, angiogenesis, and metastasis.

How do EMT derivatives affect the PI3K/AKT/mTOR pathway according to the review?

The review reports that EMT derivatives suppress PI3K/AKT/mTOR pathway activity across several cancers, including liver, gastric, acute myeloid leukaemia, and brain. Reported IC50 values range from 0.0244 to 1 μM.

What safety concerns limit clinical translation of EMT?

Known dose-dependent adverse effects include cardiotoxicity and emetic responses at higher doses. These findings indicate the need for careful dose optimization before clinical translation.

Sep 22, 2026

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