{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T06:45:38Z","timestamp":1792219538523,"version":"4.4.0"},"reference-count":122,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Anticancer drug discovery needs serious attention to overcome the high mortality rate caused by cancer. There are still many obstacles to treating this disease, such as the high cost of chemotherapeutic drugs, the resulting side effects from the drug, and the occurrence of multidrug resistance. Herbaceous plants are a reservoir of natural compounds that can be anticancer drugs with novel mechanisms of action. Piperine, a bioactive compound derived from\n                    <jats:italic>Piper<\/jats:italic>\n                    species, is gaining attention due to its unique dual role in directly inhibiting tumor growth and enhancing the bioavailability of chemotherapeutic drugs. Unlike conventional treatments, Piperine exhibits a novel mechanism of action by modulating multiple signaling pathways, including apoptosis and autophagy, with low toxicity. Additionally, Piperine acts as a bioenhancer by improving the absorption and effectiveness of other anticancer agents, reducing the required dosage, and minimizing side effects. Therefore, this review aims to visualize a summary of Piperine sources, phytochemistry, chemical structure\u2013anticancer activity relationship, anticancer activities of semi\u2010synthetic derivatives, pharmacokinetic and bioavailability, in vitro and in vivo preclinical studies, mechanism of antitumor action, human clinical trials, toxicity, side effects, and safety of Piperine. References were collected from the Pubmed\/MedLine database (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/\">https:\/\/pubmed.ncbi.nlm.nih.gov\/<\/jats:ext-link>\n                    ) with the following keywords: \u201cPiperine anticancer,\u201d \u201cPiperine derivatives,\u201d \u201cPiperine antitumor mechanism\u201d and \u201cPiperine pharmacokinetic and bioavailability,\u201d after filter process by inclusion and exclusion criteria, 101 were selected from 444 articles. From 2013 to 2023, there were numerous studies regarding preclinical studies of Piperine of various cell lines, including breast cancer, prostate cancer, lung cancer, melanoma, cervical cancer, gastric cancer, osteosarcoma, colon cancer, hepatocellular carcinoma, ovarian cancer, leukemia, colorectal cancer, and hypopharyngeal carcinoma. In vivo, the anticancer study has also been conducted on some animal models, such as Ehrlich carcinoma\u2010bearing mice, Ehrlich ascites carcinoma cells\u2010bearing Balbc mice, hepatocellular carcinoma\u2010bearing Wistar rat, A375SM cells\u2010bearing mice, A375P cells\u2010bearing mice, SNU\u201016 cells\u2010bearing BalbC mice, and HGC\u201027\u2010bearing baby mice. Treatment with this compound leads to cell proliferation inhibition and induction of apoptosis. Piperine has been used for clinical trials of diseases, but no cancer patient report exists. Various semi\u2010synthetic derivatives of Piperine show efficacy as an anticancer drug across multiple cell lines. Piperine shows promise for use in cancer clinical trials, either as a standalone treatment or as a bioenhancer. Its bioenhancer properties may enhance the efficacy of existing chemotherapeutic agents, providing a valuable foundation for developing new anticancer therapies.\n                  <\/jats:p>","DOI":"10.1002\/biof.2134","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T16:19:24Z","timestamp":1730132364000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Piperine: an emerging biofactor with anticancer efficacy and therapeutic potential"],"prefix":"10.1002","volume":"51","author":[{"given":"Hesti Lina","family":"Wiraswati","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine Universitas Padjadjaran  Sumedang Indonesia"},{"name":"Oncology and Stem Cell Working Group, Faculty of Medicine Universitas Padjadjaran  Bandung Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilma Fauziah","family":"Ma'ruf","sequence":"additional","affiliation":[{"name":"Oncology and Stem Cell Working Group, Faculty of Medicine Universitas Padjadjaran  Bandung Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7301-8151","authenticated-orcid":false,"given":"Javad","family":"Sharifi\u2010Rad","sequence":"additional","affiliation":[{"name":"Universidad Esp\u00edritu Santo  Samborond\u00f3n Ecuador"},{"name":"Centro de Estudios Tecnol\u00f3gicos y Universitarios del Golfo  Veracruz Mexico"},{"name":"Department of Medicine, College of Medicine Korea University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Calina","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy University of Medicine and Pharmacy of Craiova  Craiova 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